Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Tohru Oishi Last modified date:2019.10.16

Professor / Organic Chemistry Group / Department of Chemistry / Faculty of Sciences


Papers
1. Masahiro Hirama, Tohru Oishi, Shô Itô, Asymmetric dihydroxylation of alkenes with osmium tetroxide
Chiral N,N′-dialkyl-2,2′-bipyrrolidine complex, Journal of the Chemical Society, Chemical Communications, 10.1039/C39890000665, 10, 665-666, 1989.01, Asymmetric osmylation of alkenes by using N,N′-dialkyl-2,2′- bipyrrolidines as the chiral ligands shows a high asymmetric induction and a marked dependence of the enantioselectivity on both the N-alkyl group and the reaction solvent..
2. Tohru Oishi, Masahiro Hirama, Highly Enantioselective Dihydroxylation of Trans-Disubstituted and Monosubstituted Olefins, Journal of Organic Chemistry, 10.1021/jo00286a002, 54, 25, 5834-5835, 1989.12, Extremely high levels of asymmetric induction have been achieved in osmium tetraoxide oxidation of trans-disubstituted and monosubstituted olefins by using chiral N,N'-dineohexyl-2,2'-bipyrrolidine ligand..
3. Tohru Oishi, Masahiro Hirama, Asymmetric OsO4 Oxidation with 2,2’-Bipyrrolidine Ligands, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.48.1006, 48, 11, 1006-1007, 1990.01.
4. Tohru Oishi, M. Hirama, L. R. Sita, S. Masamune, Synthesis of chiral 2,2'-bipyrrolidine derivatives, Synthesis, 9, 789-792, 1991, Optically pure 2,2'-bipyrrolidine (1) and its 1,1'-disubstituted derivatives have been synthesized from pyrrole and 2-pyrrolidone..
5. Tohru Oishi, Masahiro Hirama, Synthesis of chiral 2,3-disubstituted 1,4-diazabicyclo [2.2.2] octane. New ligand for the osmium-catalyzed asymmetric dihydroxylation of olefins, Tetrahedron Letters, 10.1016/S0040-4039(00)92331-1, 33, 5, 639-642, 1992.01, Chiral 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octane (DABCO) derivatives have been synthesized and utilized as a chiral ligand for the osmium-catalyzed asymmetric dihydroxylation of olefins. Optically active diols in up to 41%ee are obtained in good yields..
6. Tohru Oishi, Kyo ichiro Iida, Masahiro Hirama, Asymmetric dihydroxylation of chiral olefins. High control of diastereofacial selection, Tetrahedron Letters, 10.1016/S0040-4039(00)73639-2, 34, 22, 3573-3576, 1993.05, Highly diastereoselective dihydroxylation of 4,5-dihydroxy-2-pentenoate with osmium tetroxide using chiral N,N'-dialkyl-2,2′-bipyrrolidine ligands (1) is described. Either syn or anti selection was achieved for acetate (2d) and methyl ether (2e) by employing the enantiomeric ligands..
7. Shinji Kawata, Tohru Oishi, Masahiro Hirama, Ten-membered neocarzinostatin chromophore analogs leading to σ,σ-biradical via a cumulene intermediate, Tetrahedron Letters, 10.1016/S0040-4039(00)60739-6, 35, 26, 4595-4598, 1994.06, New neocarzinostatin chromophore analogs of 10-membered ring are synthesized. Generation of σ,σ-biradical via a cumulene intermediate has been demonstrated. The DNA-cleaving activity of the hybrid 4 is found to be 50-fold more potent than 1..
8. Tohru Oishi, Hiroki Oguri, Masahiro Hirama, Asymmetric Baylis-Hillman reactions using chiral 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octanes catalysts under high pressure conditions, Tetrahedron: Asymmetry, 10.1016/0957-4166(95)00153-G, 6, 6, 1241-1244, 1995.01, Chiral C2-symmetric 2,3-disubstituted 1,4-diazabicyclo[2.2.2]octanes (DABCOs) (1) have been utilized as catalysts for asymmetric Baylis-Hillman reactions. Optically active α-methylene-β-hydroxyalkanone was obtained in up to 47% ee. Under high pressure conditions, a remarkable enhancement of both reaction rate and enantioselectivity has been observed..
9. Hiyoshizo Kotsuki, Hiroko Kuzume, Tetsushi Gohda, Misako Fukuhara, Masamitsu Ochi, Tohru Oishi, Masahiro Hirama, Motoo Shiro, New convenient, enantiospecific synthesis of (S,S)- and (R,R)-2,2′-bipyrrolidine derivatives, Tetrahedron: Asymmetry, 10.1016/0957-4166(95)00297-3, 6, 9, 2227-2236, 1995.01, An enantiomeric pair of (S,S)- and (R,R)-bipyrrolidine derivatives has been prepared from D- and L-tartaric acids or D-mannitol as optically active starting materials. Taking advantage of the C2-symmetric nature of these chiral sources, the synthetic sequence has been established by using efficient side chain elongation, stereospecific conversion of a vicinal diol into a diazido group via SN2 inversion, and pyrrolidine ring formation via intramolecular substitution as the key steps..
10. Tohru Oishi, Toshihiro Iwakuma, Masahiro Hirama, Shô Itô, Stereoselective Synthesis of (+)-Swainsonine and (-)-8,8a-Di-epi -swainsonine, Synlett, 10.1055/s-1995-5002, 1995, 5, 404-406, 1995.05, (+)-Swainsonine 2 and (-)-8,8a-di-epi-swainsonine 3 were stereoselectively synthesized from L-glutamic acid via a highly diastereoselective intramolecular conjugate addition of amide 20 and carbamate 8, respectively. Another key step is a stereoselective osmium-catalyzed dihydroxylation of indolizidine double bond..
11. Hiroki Oguri, Shojiro Hishiyama, Tohru Oishi, Masahiro Hirama, Enantio-Controlled Synthesis of the AB Ring Moiety of Ciguatoxin, Synlett, 10.1055/s-1995-5259, 1995, 12, 1252-1254, 1995.12, The AB ring fragment 15 of ciguatoxin (1) has been synthesized enantioselectively from D-glucose..
12. Koji Toyama, Satoru Iguchi, Tohru Oishi, Masahiro Hirama, Expeditious Synthesis of Enantiomerically Pure trans -4,5-Dihydroxy-2-cyclopenten-1-one, Synlett, 10.1055/s-1995-5261, 1995, 12, 1243-1244, 1995.12, A short-step synthesis of (-)-(4R,5S)- and (+)-(4S,5R)-trans-4,5-dihydroxy-2-cyclopenten-1-one derivatives (14) has been achieved via the enzymatic asymmetric transformations of meso-3,4,5-trans,trans-trihydroxycyclopentene derivatives 12 and 15, respectively..
13. Tohru Oishi, Mitsuru Shoji, Kenji Maeda, Naomi Kumahara, Masahiro Hirama, Extensive Ring-Expansion Strategy for the Enantioselective Synthesis of the Medium Ring Ethers, Oxepene, Oxocane, and Oxonene, of Ciguatoxin, Synlett, 10.1055/s-1996-5729, 1996, 12, 1165-1167, 1996.01, The extensive ring-expansion strategy for the synthesis of oxepene 19, oxocane 23, and oxonene 28, which correspond to the D (E), I and F ring fragments of ciguatoxin (1), respectively, has been established. Chemoenzymatic asymmetric acylation of the meso alcohols using lipase AK provided a simple entry of the enantiomeric building blocks..
14. Tohru Oishi, Yoko Nagumo, Masahiro Hirama, Convergent Synthesis of a Trans-fused 6-7-6 Tricyclic Ether System Based on a Ring-closing Metathesis Reaction, Synlett, 10.1055/s-1997-969, 1997, 8, 980-982, 1997.01, Synthesis of a trans-fused 6-7-6 tricyclic ether system was achieved via stereoselective acetal formation, reductive cleavage of the acetal, and a ring-closing metathesis reaction..
15. Tohru Oishi, Kenji Maeda, Masahiro Hirama, Stereocontrolled synthesis of the HIJ ring system of ciguatoxin, Chemical Communications, 10.1039/a702158e, 14, 1289-1290, 1997.01, Divergent synthesis of the HIJ ring framework 21 of ciguatoxin 1 starting with oxocane 10 is achieved using the palladium- and acid-catalysed cyclization reactions of hydroxy epoxides..
16. Tohru Oishi, Mitsuru Shoji, Naomi Kumahara, Masahiro Hirama, Stereoselective synthesis of the LM ring moiety of ciguatoxin
Reagent control of asymmetric dihydroxylation, Chemistry Letters, 10.1246/cl.1997.845, 9, 845-846, 1997.01, Stereoselective synthesis of the LM ring moiety of ciguatoxin was achieved from (R)-(E)-1-benzyloxy-2-hydroxy-3-pentene via Ireland-Claisen rearrangement, iodolactonization, and reagent-controlled asymmetric dihydroxylation..
17. M. Satake, A. Morohashi, H. Oguri, Tohru Oishi, M. Hirama, N. Harada, T. Yasumoto, The absolute configuration of ciguatoxin, Journal of the American Chemical Society, 10.1021/ja972482t, 119, 46, 11325-11326, 1997.01.
18. Hiroki Oguri, Shojiro Hishiyama, Ohki Sato, Tohru Oishi, Masahiro Hirama, Michio Murata, Takeshi Yasumoto, Nabuyuki Harada, Synthetic study of ciguatoxin. Absolute configuration of the C2 hydroxy group, Tetrahedron, 10.1016/S0040-4020(97)00071-9, 53, 9, 3057-3072, 1997.03, The absolute stereochemistry of the secondary alcohol of the 1,2-dihydroxybutenyl substituent of ciguatoxin (1) was shown to be S by comparing (he split CD curve of ciguatoxin tetra-p-bromobenzoate (2) with those of di- and tri-p-bromobenzoates of AB ring fragments that were synthesized enaotioselectively..
19. Tohru Oishi, Yoko Nagumo, Masahiro Hirama, Convergent synthesis of the trans-fused 6-n-6-6 (n = 7-10) tetracyclic ether system based on a ring-closing metathesis reaction, Chemical Communications, 10.1039/a801678j, 9, 1041-1042, 1998.05, A convergent synthesis of the trans-fused 6-n-6-6 (n = 7-10) tetracyclic ether system was achieved via stereoselective alkylation and ring-closing metathesis reaction..
20. Hiroki Oguri, Shin Ichiro Tanaka, Shojiro Hishiyama, Tohru Oishi, Masahiro Hirama, Takeshi Tumuraya, Yoshihisa Tomioka, Michinao Mizugaki, Designed hapten aimed at anti-ciguatoxin monoclonal antibody
Synthesis, immunization and discrimination of the C2 configuration, Synthesis, SPEC. ISS., 1431-1436, 1999.01, The ABC-ring fragment of ciguatoxin was synthesized as a C2 epimeric mixture (1:1). The mixture, which was designed as a possible hapten for preparing an anti-ciguatoxin monoclonal antibody was conjugated with a carrier protein (KLH) and then used for immunization of mice. The three monoctonal antibodies (mAbs) obtained have shown an appreciable reactivity to the hapten. Each mAb discriminated configuration of the C2 hydroxy group of the ABC-ring fragment. The mAb which showed reactivity to the 2S-fragment was cross-reacted with ciguatoxin..
21. Kenji Maeda, Tohru Oishi, Hiroki Oguri, Masahiro Hirama, Convergent synthesis of the ABCDE ring framework of ciguatoxin, Chemical Communications, 10.1039/a903063h, 12, 1063-1064, 1999.06, An alkylation-metathesis sequence is shown to be a powerful method to synthesize the ABCDE ring framework of ciguatoxin 1..
22. Tohru Oishi, Megumi Maruyama, Mitsuru Shoji, Kenji Maeda, Naomi Kumahara, Shin Ichiro Tanaka, Masahiro Hirama, Enantioselective synthesis of the medium ring ethers, tetrahydrooxepin, oxocane and hexahydrooxonin, of ciguatoxin. Extensive ring-expansion and chemoenzymatic desymmetrization strategy, Tetrahedron, 10.1016/S0040-4020(99)00370-1, 55, 24, 7471-7498, 1999.06, The extensive ring-expansion strategy for the synthesis of tetrahydrooxepin, oxocane, and hexahydrooxonin, which correspond to the D(E), I and F rings of ciguatoxin (CTX1B, 1). respectively, has been established. Chemoenzymatic acylation of the meso alcohols using a lipase provides an expeditious entry for the enantiomeric building blocks..
23. Hiroki Oguri, Shin ya Sasaki, Tohru Oishi, Masahiro Hirama, Expeditious tandem-metathesis route to the AB-ring fragment of ciguatoxin, Tetrahedron Letters, 10.1016/S0040-4039(99)01017-5, 40, 29, 5405-5408, 1999.07, The AB-ring fragment of ciguatoxin was synthesized in ten steps from tri-O-benzyl-D-glucal based on a highly diastereoselective ring-closing metathesis and subsequent cross metathesis..
24. Tohru Oishi, Yoko Nagumo, Mitsuru Shoji, Jean Yves Le Brazidec, Hisatoshi Uehara, Masahiro Hirama, Convergent synthesis of the IJKLM ring fragment of ciguatoxin CTX3C, Chemical Communications, 10.1039/a906834a, 20, 2035-2036, 1999.10, The IJKLM ring fragment of CTX3C, an important member of the ciguatoxin family, was synthesized via ring-closing metathesis using the Tebbe reagent and an improved method of reductive hydroxy ketone cyclization..
25. Hisatoshi Uehara, Tohru Oishi, Kazuhiro Yoshikawa, Kenichi Mochida, Masahiro Hirama, The absolute configuration and total synthesis of korormicin, Tetrahedron Letters, 10.1016/S0040-4039(99)01812-2, 40, 49, 8641-8645, 1999.12, The marine antibiotic korormicin, isolated from the culture filtrate of marine bacterial strain Pseudoalteromonas sp. F-420, specifically inhibits the growth of marine Gram-negative bacteria without affecting terrestrial species. The absolute configuration of korormicin was determined by the combination of a CD exciton chirality method and chemical degradation. Convergent total synthesis of korormicin has been also achieved..
26. S. Toujima, K. Kuwano, Y. Zhang, N. Fujimoto, M. Hirama, Tohru Oishi, S. Fukuda, Y. Nagumo, H. Imai, T. Kikuchi, S. Arai, Binding of glycoglycerolipid derived from membranes of Acholeplasma laidlawii PG8 and synthetic analogues to lymphoid cells, Microbiology, 10.1099/00221287-146-9-2317, 146, 9, 2317-2323, 2000.01, A component that binds to human lymphoid cells was isolated from the membranes of Acholeplasma laidlawii PG8. The component was extracted using the Bligh-Dyer method and purified using a silica-gel column and TLC. The active component was identified as 3-O-[2'-O- (α-D-glucopyranosyl)-6'-O-acyl-α-D-glucopyranosyl]-1, 2-di-O-acyl-sn-glycerol (GAGDG) using 1H- and 13C-NMR and GC-MS. The compositions of the major saturated fatty acids were nC14 (17·8%), isoC14 (10·7%) and nC16 (34·9%) as determined by GC-MS. The amounts of unsaturated species were less than 10% of those of the corresponding saturated acids. GAGDGs which have three tetradecanoyl groups were synthesized. These synthetic GAGDGs, as well as GAGDGs derived from A. laidlawii membranes, had a high binding affinity for MOLT-4 and HUT-78 (human T cell lines), Raji (a B cell line), HL-60 (a monoblastoid cell line) and primary cultured human T cells. The binding affinities of GAGDGs with an isoC14 acyl group was higher than those with nC14 and nC16 acyl groups. The binding to lymphoid cells reveals a novel biological activity of GAGDGs..
27. Hiroki Oguri, Shin Ichiro Tanaka, Tohru Oishi, Masahiro Hirama, A very short route to the functionalized A-ring moiety of ciguatoxin, Tetrahedron Letters, 10.1016/S0040-4039(99)02185-1, 41, 6, 975-978, 2000.02, The functionalized AB-ring moiety of ciguatoxin has been synthesized in a highly convergent manner via transition metal catalysis. (C) 2000 Elsevier Science Ltd..
28. Kaori Ando, Tohru Oishi, Masahiro Hirama, Hiroaki Ohno, Toshiro Ibuka, Z-selective Horner-Wadsworth-Emmons reaction of ethyl (diarylphosphono)acetates using sodium iodide and DBU, Journal of Organic Chemistry, 10.1021/jo000068x, 65, 15, 4745-4749, 2000.07.
29. Hiroto Imai, Tohru Oishi, Tsukasa Kikuchi, Masahiro Hirama, Concise synthesis of 3-O-(2-O-α-D-glucopyranosyl-6-O-acyl-α-D-glucopyranosyl)-1,2-di-O-acyl-sn-g lycerols, Tetrahedron, 10.1016/S0040-4020(00)00793-6, 56, 43, 8451-8459, 2000.10, A versatile synthetic route to 3-O(2-O-α-D-glucopyranosyl-6-O-acyl-α-D-glucopyranosyl)-1,2-di-O-acyl-sn-gl ycerols, which should provide various acyl derivatives, has been developed. (C) 2000 Elsevier Science Ltd..
30. Megumi Maruyama, Kenji Maeda, Tohru Oishi, Hiroki Oguri, Masahiro Hirama, Convergent strategy for synthesizing polycyclic ether marine toxins
Synthesis of the ABCDE ring fragment of ciguatoxin CTX3C, Heterocycles, 54, 1, 93-99, 2001.01, The ABCDE ring fragment of CTX3C, the most important member of the ciguatoxin family, was concisely synthesized by extensive use of ring-closing olefin metathesis..
31. Tohru Oishi, H. Uehara, Y. Nagumo, M. Shoji, J. Y. Le Brazidec, M. Kosaka, M. Hirama, Practical entry into the HIJKLM ring segment of ciguatoxin CTX3C, Chemical Communications, 10.1039/b009506k, 4, 381-382, 2001.02, The HIJKLM ring segment (27) of the right half portion of ciguatoxin CTX3C (1) has been synthesized using a ring-closing reaction mediated by a low-valent titanium reagent..
32. K. Toyama, S. Iguchi, H. Sakazaki, Tohru Oishi, M. Hirama, Convenient route to both enantiomerically pure forms of trans-4,5-dihydroxy-2-cyclopenten-1-one
Efficient synthesis of the neocarzinostatin chromophore core, Bulletin of the Chemical Society of Japan, 10.1246/bcsj.74.997, 74, 6, 997-1008, 2001.06, An enantioselective synthesis of an epoxybicyclo[7.3.0]dodecenediyne core system of the neocarzinostatin chromophore has been achieved via intramolecular acetylide addition and palladium-mediated coupling of iodocyclopentene 5 with alkyne 6. The key cyclopentene moiety, trans-4,5-dihydroxy-2-cyclopenten-1-one 7, was conveniently prepared in both enantiomerically pure forms via enzymatic desymmetrization of meso-3,4,5-trans,trans-trihydroxycyclopentene derivatives..
33. Tohru Oishi, S. I. Tanaka, Y. Ogasawara, K. Maeda, H. Oguri, M. Hirama, Highly stereocontrolled synthesis of the ABCD ring fragment of ciguatoxin CTX3C, Synlett, SPEC. ISS, 952-954, 2001.06, A combination of asymmetric alkylation using (1R,2S)-1-amino-2-indanol derivative as a chiral auxiliary and the ring-closing metathesis reaction was shown to be an efficient method for synthesizing the ABCD ring fragment of ciguatoxin CTX3C..
34. Yoko Nagumo, Hiroki Oguri, Yumi Shindo, Shin ya Sasaki, Tohru Oishi, Masahiro Hirama, Yoshihisa Tomioka, Michinao Mizugaki, Takeshi Tsumuraya, Concise synthesis of ciguatoxin ABC-ring fragments and surface plasmon resonance study of the interaction of their BSA conjugates with monoclonal antibodies, Bioorganic and Medicinal Chemistry Letters, 10.1016/S0960-894X(01)00358-4, 11, 15, 2037-2040, 2001.08, Monoclonal antibodies (mAbs), 4H2 and 6H7, were prepared previously using a protein conjugate of a 1:1 epimeric mixture of the synthetic ABC-ring fragments of ciguatoxin (CTX), 3 and 4. Here, the interactions of these mAbs with the fragments of CTX and CTX3C, 3 and 5, were investigated by surface plasmon resonance (SPR) spectroscopy in an attempt to clarify an antigenic determinant. Compared with the previous synthesis, the fragment 3 possessing the 2S configuration was synthesized from tri-O-acetyl-D-glucal much more effectively. The mAb 4H2 was already known to show a dose-dependent binding to the bovine serum albumin (BSA) conjugate of 3, but not to that of 5. The present SPR study of 4H2 demonstrates that the A-ring side chain of 3 plays a decisive role as an epitope. Therefore, SPR can effectively replace the ELISA method for the analysis of mAbs..
35. Hiroto Imai, Hisatoshi Uehara, Masayuki Inoue, Hiroki Oguri, Tohru Oishi, Masahiro Hirama, Convergent synthesis of the EFGH ring fragment of ciguatoxin CTX3C, Tetrahedron Letters, 10.1016/S0040-4039(01)01219-9, 42, 35, 6219-6222, 2001.08, A stereoselective synthesis of the EFGH ring fragment of ciguatoxin CTX3C has been achieved through: (i) selective cleavage of a dioxepane acetal C-O bond; (ii) radical cyclization to form the oxepane G ring; and (iii) chemoselective ring-closing metathesis of a triene yielding the hexahydrooxonin F ring..
36. M. Hirama, Tohru Oishi, H. Uehara, M. Inoue, M. Maruyama, H. Oguri, M. Satake, Total synthesis of ciguatoxin CTX3C, Science, 10.1126/science.1065757, 294, 5548, 1904-1907, 2001.11, More than 20,000 people suffer annually from ciguatera seafood poisoning in subtropical and tropical regions. The extremely low content of the causative neurotoxins, designated as ciguatoxins, in fish has hampered the isolation, detailed biological studies, and preparation of anti-ciguatoxin antibodies for detecting these toxins. The large (3 nanometers long) and complicated molecular structure of ciguatoxins has impeded chemists from completing their total synthesis. Our highly convergent strategic approach featuring the chemoselective ring-closing metathesis reaction as a key tactic has enabled the total synthesis of ciguatoxin CTX3C, which will provide a practical supply for further studies..
37. Megumi Maruyama, Masayuki Inoue, Tohru Oishi, Hiroki Oguri, Yoshihiro Ogasawara, Yumi Shindo, Masahiro Hirama, Convergent synthesis of the ABCDE ring system of ciguatoxin CTX3C, Tetrahedron, 10.1016/S0040-4020(02)00041-8, 58, 10, 1835-1851, 2002.03, Ciguatoxin CTX3C is a representative congener of the ciguatoxins, which are known to be the principal causative-agents of ciguatera seafood poisoning. The structure of CTX3C spans over three nanometers and is characterized by thirteen ether rings. To attain a practical construction of this molecule, efficient supplies of the structural fragments are crucial. Herein we report the convergent synthesis of the ABCDE ring fragment featuring (i) alkylative coupling of the AB ring and E ring, and (ii) ring-closing olefin metathesis..
38. Nobuaki Matsumori, Nahoko Yamaji, Shigeru Matsuoka, Tohru Oishi, Michio Murata, Amphotericin B covalent dimers forming sterol-dependent ion-permeable membrane channels, Journal of the American Chemical Society, 10.1021/ja012026b, 124, 16, 4180-4181, 2002.04, Polyenemacrolides such as amphotericin B (AmB) were thought to assemble together and form an ion channel across plasma membranes. Their antimicrobial activity has been accounted for by this assemblage, whose stability and activity are dependent on sterol constituents of lipid bilayer membranes. The structure of this channel-like assemblage formed in biomembranes has been a target of extensive investigations for a long time. For the first step to this goal, we prepared several AmB dimers with various linkers and tested for their channel-forming activity. Among these, AmB dimers that bore an aminoalkyl-dicarboxylate tether covalently linked between amino groups of AmB showed potent hemolytic activity. Furthermore, K+ influx actions monitored by measuring the pH of the liposome lumen by 31P NMR revealed that the dimers formed the molecular assemblage similar to that of AmB in phospholipid membrane. Judging from changes in 31P NMR spectra, the dimers appeared to induce "all-or-none"-type ion flux across the liposome membrane in the presence of ergosterol, which suggested that the ion channel formed by ergosterol/dimer is similar to that of AmB. With these data in hand, we are now trying to elucidate the structure of the ion-channel complex by making the labeled conjugates of AmB for NMR measurements..
39. Nahoko Yamaji, Nobuaki Matsumori, Shigeru Matsuoka, Tohru Oishi, Michio Murata, Amphotericin B Dimers with Bisamide Linkage Bearing Powerful Membrane-Permeabilizing Activity, Organic Letters, 10.1021/ol025982m, 4, 12, 2087-2089, 2002.06, (Matrix Presented) Covalently linked dimers of amphotericin B were prepared by cross-linking its carboxylic acid. Among these, a dimer with a linkage of 1,6-hexanediamine revealed potent hemolytic activity (EC50,0.25 μM) while its N-acetyl derivative gave rise to large K+ ion flux in phosphatidylcholine liposomes, regardless of the presence or absence of sterols, suggesting that the dimers may serve as a tool for elucidating the structure of the ion channel assemblage formed by amphotericin B..
40. Hisatoshi Uehara, Tohru Oishi, Masayuki Inoue, Mitsuru Shoji, Yoko Nagumo, Masashi Kosaka, Jean Yves Le Brazidec, Masahiro Hirama, Convergent synthesis of the HIJKLM ring fragment of ciguatoxin CTX3C, Tetrahedron, 10.1016/S0040-4020(02)00660-9, 58, 32, 6493-6512, 2002.08, Ciguatoxin CTX3C is a representative congener of the ciguatoxins, which are known to be the principal causative agents of ciguatera food poisoning. The structure of CTX3C spans more than 3nm and is characterized by 13 ether rings. To attain a practical construction of this molecule, efficient supplies of the structural fragments are crucial. Herein we report the convergent synthesis of the HIJKLM ring fragment and present a new carbonyl olefination protocol to cyclize the J ring using low-valent titanium..
41. Tohru Oishi, Total synthesis of ciguatoxin CTX3C, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.61.562, 61, 6, 562-571, 2003.01, Ciguatoxins are the causative neurotoxins of ciguatera seafood poisoning, and more than 20,000 people suffer annually from ciguatera disease in subtropical and tropical regions. The extremely low content of ciguatoxins in fish has hampered the isolation and detailed biological studies. The complicated and huge, 3 nm long, molecular structure of ciguatoxins has impeded synthetic chemists from completing their total syntheses, which are formidable synthetic challenge in modern organic synthesis. Our highly convergent strategic approach featuring the chemoselective ring closing metathesis (RCM) reaction as a key tactics, (i) alkylative coupling and RCM, (ii) intramolecular carbonyl olefination and reductive etherification, (iii) chemo- and regioselective radical cyclization and RCM, has enabled the first total synthesis of ciguatoxin CTX 3 C, which will provide the practical supply for further studies..
42. Tohru Oishi, Hiroshi Tsuchikawa, Michio Murata, Manabu Yoshida, Masaaki Morisawa, Synthesis of endogenous sperm-activating and attracting factor isolated from ascidian Ciona intestinalis, Tetrahedron Letters, 10.1016/S0040-4039(03)01598-3, 44, 34, 6387-6389, 2003.08, A chemoattractant candidate named sperm-activating and attracting factor (SAAF) from the eggs of ascidian Ciona intestinalis, was synthesized from chenodeoxycholic acid in 16 steps. The present synthesis led to the unambiguous structure determination of SAAF to be (3R,4R,7R,25S)-3,4,7,26-tetrahydroxycholestane-3,26-disulfate. The synthetic pure specimen was also used to confirm the dual sperm-activating and attracting activity..
43. Tohru Oishi, Koji Watanabe, Michio Murata, Convergent synthesis of trans-fused 6/n/6/6 (n=7, 8) tetracyclic ether system via α-cyano ethers, Tetrahedron Letters, 10.1016/S0040-4039(03)01862-8, 44, 39, 7315-7319, 2003.09, A convergent method for synthesizing 6/n/6/6 (n=7, 8) tetracyclic ether system via two-rings construction of the central n/6 ring system was developed. The key steps of the present synthesis involve a ring-closing metathesis reaction for the construction of the seven- and eight-membered rings, and reductive etherification for the tetrahydropyrans. Unification of the two fragments through acetal formation, followed by regioselective cleavage of the acetal using TMSCN/TMSOTf in the presence of 2,6-di-tert-butyl-4-methylpyridine, afforded the α-cyano ether, of which the nitrile group was manipulated to give the precursors of the ring-closing reactions..
44. Nobuaki Matsumori, Noritsugu Eiraku, Shigeru Matsuoka, Tohru Oishi, Michio Murata, Takaaki Aoki, Toru Ide, An amphotericin B-ergosterol covalent conjugate with powerful membrane permeabilizing activity, Chemistry and Biology, 10.1016/j.chembiol.2004.02.027, 11, 5, 673-679, 2004.05, Amphotericin B-sterol conjugates were synthesized and examined for their membrane permeabilizing activity. Ergosterol and cholesterol, each connected with amphotericin B via an ethylenecarbamate or hexamethylenecarbamate linker, were examined by K+ flux assays using liposomes and by single-channel recording across phospholipid membrane. Among four conjugates tested, AmB-ergosterol bearing an ethylenecarbamate linker exhibited the most powerful activity, which substantially exceeded that of the cholesterol homolog. Single-channel recording clearly exhibited that the ergosterol conjugate elicited channel current with the conductance of 28 pS, which was comparable with those by AmB, and revealed a higher channel open probability than the cholesterol conjugate. These results imply that direct interaction between amphotericin B and ergosterol is reproduced by their conjugate, which may serve as a model compound for understanding the drug's selective toxicity..
45. Keisuke Maruyoshi, Tetsuo Demura, Takeshi Sagane, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Synthesis and conformation of deuterated spermidine for investigating weak interaction with polyanionic biomolecules, Tetrahedron, 10.1016/j.tet.2004.04.056, 60, 24, 5163-5170, 2004.06, Polyamines such as spermidine and spermine are known to interact with polyanionic biomolecules under physiological conditions. Conformation analysis of these highly flexible acycles is virtually unprecedented due to the lack of appropriate methodologies. Spin-spin coupling constants, which are often utilized for acyclic systems, are rather uninformative for polyamines due to unresolved 1H NMR signals of their tri- and tetra-methylene moieties. We attempted to solve this problem by synthesizing diastereospecifically deuterated spermidine, (1S*,2S*)-1,8-diamino- 4-azaoctane-1,2,3,3,5,5,6,6,7,7,8,8-d12. To evaluate its utility, 1H-1H spin coupling constants were measured as trihydrochloride or tripolyphosphate salt. The relevant coupling constant markedly decreased upon complexation to tripolyphosphate. Under neutral pH, where the net charge of tripolyphosphate became tetravalent, the coupling constant was small; as pH was lowered to 1.4, where the charge was divalent, the constant increased significantly. These data clearly indicate that, when interacting with polyanions, spermidine undergoes conformational changes to increase bent conformation, which could be effectively monitored by the deuterated spermidine..
46. Tohru Oishi, Hiroshi Tsuchikawa, Michio Murata, Manabu Yoshida, Masaaki Morisawa, Synthesis and identification of an endogenous sperm activating and attracting factor isolated from eggs of the ascidian Ciona intestinalis; An example of nanomolar-level structure elucidation of novel natural compound, Tetrahedron, 10.1016/j.tet.2004.02.075, 60, 33, 6971-6980, 2004.08, A sperm-activating and attracting factor (SAAF) was isolated from the eggs of the ascidian Ciona intestinalis, and its structure was deduced with only approximately 4 μg of the specimen. Based upon the proposed structure, two epimers were synthesized from chenodeoxycholic acid in 16 steps. Comparison between synthetic and natural compounds led to the unambiguous structure determination of SAAF to be (3R,4R,7R,25S)-3,4,7,26-tetrahydroxycholestane-3,26- disulfate. The synthetic pure specimen was also utilized to confirm that both sperm-activation and attraction were elicited by a single compound..
47. Shoji Kobayashi, Yusuke Takahashi, Kazuo Komano, Babak H. Alizadeh, Yuuya Kawada, Tohru Oishi, Shin Ichiro Tanaka, Yoshihiro Ogasawara, Shin Ya Sasaki, Masahiro Hirama, Stereocontrolled synthesis of the ABCDE ring moiety of ciguatoxin CTX3C, Tetrahedron, 10.1016/j.tet.2004.07.010, 60, 38, 8375-8396, 2004.09, The ABCDE ring moiety of ciguatoxin CTX3C, a major causative agent of ciguatera poisoning, was stereoselectively synthesized. The key transformations are a chiral auxiliary-based asymmetric alkylation and an asymmetric aldol condensation, which controlled the formation of the C11 and C21-stereocenters, respectively. A highly practical and efficient route to the ABCD ring fragment, a common precursor for the divergent synthesis of the left wings of ciguatoxins, was also established. Graphical Abstract..
48. Hiroaki Yamada, Tomoko Sasaki, Sachiko Niwa, Tohru Oishi, Michio Murata, Toru Kawakami, Saburo Aimoto, Intact glycation end products containing carboxymethyl-lysine and glyoxal lysine dimer obtained from synthetic collagen model peptide, Bioorganic and Medicinal Chemistry Letters, 10.1016/j.bmcl.2004.08.044, 14, 22, 5677-5680, 2004.11, Glycation reactions using a model peptide of collagen and glucose or ribose resulted in detection of carboxylmethyl-lysine in the peptide; and treatment with glyoxal provided a dimer of the peptide linked with glyoxal lysine dimer (GOLD). Advanced glycation end products (AGE) are accumulated in human tissues when long-lived proteins are glycated due to hyperglycemia and/or aging. In this study, we synthesized a collagen model peptide, Ac-(Pro-Hyp-Gly) 5-Pro-Lys-Gly-(Pro-Hyp-Gly) 5-Ala-NH 2 to investigate intact AGEs in peptides. The peptide formed a stable triple helix structure, and was subjected to glycation reactions with glucose, ribose and glyoxal. Besides carboxymethyl-lysine in the peptide, a conjugated form linked with glyoxal lysine dimer (GOLD) was detected upon treatment with glyoxal. This is the first example of intact glycation-derived dimers of peptides retaining intrinsic protein structures..
49. Takashi Shimizu, Sumio Arai, Hiroto Imai, Tohru Oishi, Masahiro Hirama, Atsushi Koito, Yutaka Kida, Koichi Kuwano, Glycoglycerolipid from the membranes of Acholeplasma laidlawii binds to human immunodeficiency virus-1 (HIV-1) and accelerates its entry into cells, Current Microbiology, 10.1007/s00284-003-4101-x, 48, 3, 182-188, 2004.12, We have reported previously that glycoglycerolipids derived from the membranes of Acholeplasma laidlawii, 3-O-[2′-O-(α-D-glucopyranosyl)- 6′-O-acyl-α-glucopyranosyl]-1,2-di-O-acyl-sn-glycerols (GAGDGs) bind to human cell lines. In addition, the GAGDGs were found to augment HIV-1 infection in human cell lines. Here we show that GAGDG binds to HIV-1 and facilitates the entry of HIV-1 into cells. The binding ability of GAGDG to HIV-1 was blocked by anti-GAGDG serum. Binding assay with synthetic GAGDGs and related compounds showed that the presence of branching form of acyl chains at the C14 or C16 position, glucose, and the acyl chain binding to the glucose were critical for efficient binding. GAGDG efficiently augmented the entry of HIV-1 into cells in a single-cycle replication assay. These results indicate that GAGDG of A. laidlawii membranes participates in the facilitation of HIV-1 infection..
50. Koji Watanabe, Miho Suzuki, Michio Murata, Tohru Oishi, Convergent synthesis of the FGHI ring system of yessotoxin
Stereoselective construction of the G ring, Tetrahedron Letters, 10.1016/j.tetlet.2005.04.040, 46, 23, 3991-3995, 2005.06, A convergent synthetic route to the FGHI ring system of yessotoxin, a marine ladder polyether, has been developed. The synthesis features convergent coupling of the diol and the aldehyde to form α-cyano ethers via acetal formation followed by ring closing metathesis and reductive etherification to construct the oxocane ring G and tetrahydropyran ring H, respectively. The β-methyl group on the G ring was stereoselectively introduced by alkylation of the corresponding ketone..
51. Nobuaki Matsumori, Yuichi Umegawa, Tohru Oishi, Michio Murata, Bioactive fluorinated derivative of amphotericin B, Bioorganic and Medicinal Chemistry Letters, 10.1016/j.bmcl.2005.05.058, 15, 15, 3565-3567, 2005.08, The first stably fluorinated derivative of amphotericin B (2) with a fluorine atom in the macrolide skeleton was synthesized using an electrophilic fluorination reagent, Selectfluor®. The derivative 2 showed hemolytic, K+ permeable, and antifungal activities similar to those of AmB and thus was expected to be a powerful tool for NMR-based investigations on the mechanism of ion-channel formation by amphotericin B..
52. Megumi Mori, Tohru Oishi, Shigeru Matsuoka, Satoru Ujihara, Nobuaki Matsumori, Michio Murata, Masayuki Satake, Yasukatsu Oshima, Nobuto Matsushita, Saburo Aimoto, Ladder-shaped polyether compound, desulfated yessotoxin, interacts with membrane-integral α-helix peptides, Bioorganic and Medicinal Chemistry, 10.1016/j.bmc.2005.05.039, 13, 17, 5099-5103, 2005.09, Ladder-shaped polyether compounds, represented by brevetoxins, ciguatoxins, maitotoxin, and prymnesins, are thought to possess the high affinity to transmembrane proteins. As a model compound of ladder-shaped polyethers, we adopted desulfated yessotoxin (2) and examined its interaction with glycopholin A, a membrane protein known to form a dimer or oligomer. Desulfated yessotoxin turned out to interact with the α-helix so as to induce the dissociation of glycopholin oligomers when examined by SDS and PFO gel electrophoresis. The results provided the first evidence that lapper-shaped polyethers interact with transmembrane helix domains..
53. M. Murata, Tohru Oishi, M. Yoshida, State-of-art methodology of marine natural products chemistry
structure determination with extremely small sample amounts., Progress in molecular and subcellular biology, 42, 203-220, 2006.01, Structure elucidation studies on natural products are reviewed emphasizing extremely small sample amounts. Previous studies on insect pheromones, periplanones, and bean-originating kairomones, glycinoeclepins, are described briefly. Recent examples are selected from marine natural products such as ciguatoxin, dolastatin-3, and aurisides. A more detailed description is given of a sperm-activating and attracting factor (SAAF), which may be the smallest sample amount used in the structure elucidation of novel non-peptidic natural products. SAAF was isolated from the eggs of the ascidian, Ciona intestinalis, and its structure was deduced with only approximately 4 microg (6 nmol) of sample. Based upon the proposed structure, two epimers were synthesized from chenodeoxycholic acid in 17 steps, leading to the identification of SAAF as a novel sterol sulfate..
54. Nobuaki Matsumori, Tohru Oishi, Michio Murata, Derivatization and isotope labeling of amphotericin B aiming at elucidation of the ion-channel structure, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 64, 5, 502-513, 2006.05, Amphotericin B (AmB) is known to assemble together and form an ion channel across biomembranes. The selective toxicity is generally accounted for by its higher affinity for ergosterol than cholesterol. To better understand the ion-channel structure and intermolecular interactions, we prepared various AmB derivatives and measured their activities. AmB dimers which are covalently linked between the amino groups by short chains showed more potent ion-channel activity than that of AmB, indicating that the mutual topology of AmB molecules is a head-to-head orientation. AmB-sterol conjugates were also designed and examined for ion-channel activities. AmB-ergosterol conjugates showed more powerful ion-channel activity than AmB-cholesterol congeners, suggesting that stronger van der Waals interaction between AmB and ergosterol contributes to the higher ion-channel activity. Finally, we prepared conformation-restricted derivatives of AmB, in which the amino and carboxyl groups were bridged with various lengths of alkyl chains. The derivatives successfully gave us information on the active-conformation of the sugar moiety of AmB in membrane. These derivatives are now labeled by 13C and/or 19F to probe the molecular structure of AmB ion channel using solid-state NMR..
55. Tohru Oishi, Miho Suzuki, Koji Watanabe, Michio Murata, Synthesis of the ABC and IJ ring fragments of yessotoxin, Tetrahedron Letters, 10.1016/j.tetlet.2006.04.018, 47, 24, 3975-3978, 2006.06, Synthesis of a 6/6/6 tricyclic ether system (3) corresponding to the ABC ring fragment of yessotoxin (1) has been achieved via coupling of a triflate and a 2-lithiofuran followed by intramolecular hetero-Michael addition. The IJ ring fragment (4) of 1 was readily synthesized via successive Sharpless epoxidation and 6-endo cyclization of the resulting vinyl epoxide..
56. Hiroshi Tsuchikawa, Naohiro Matsushita, Nobuaki Matsumori, Michio Murata, Tohru Oishi, Synthesis of 28-
19
F-amphotericin B methyl ester, Tetrahedron Letters, 10.1016/j.tetlet.2006.06.159, 47, 35, 6187-6191, 2006.08, A fluorinated amphotericin B (AmB) derivative, 28-
19
F-AmB methyl ester (3), labeled at the polyene moiety, was synthesized by combining chemical synthesis with degradation of a natural product via cross-coupling reactions and macrolactonization. The fluorinated derivative 3 showed antifungal activity similar to that of AmB, and is expected to be a powerful tool for NMR-based investigation of the mechanism of ion-channel formation..
57. Nagy Morsy, Toshihiro Houdai, Shigeru Matsuoka, Nobuaki Matsumori, Seiji Adachi, Tohru Oishi, Michio Murata, Takashi Iwashita, Tsuyoshi Fujita, Structures of new amphidinols with truncated polyhydroxyl chain and their membrane-permeabilizing activities, Bioorganic and Medicinal Chemistry, 10.1016/j.bmc.2006.06.012, 14, 19, 6548-6554, 2006.10, Two new homologues of amphidinols (AM14 and AM15) were isolated from the cultured dinoflagellate Amphidinium klebsii. The structures were elucidated on the basis of 2D NMR and collision-induced dissociation MS/MS and turned out to be closely related homologues of AM7. Their weak membrane-disrupting activity indicates that the hydrophobic polyene chain is essential for the potent biological activities. Structure-activity relationship for the polyhydroxyl part was then examined with use of AM homologues possessing various chain lengths, indicating that the pore size of the channel/lesion formed by AMs was not greatly affected by the length of the polyhydroxyl chain..
58. Tohru Oishi, Miho Suzuki, Koji Watanabe, Michio Murata, Convergent synthesis of the cdef ring fragment of yessotoxin via α-cyano ethers, Heterocycles, 10.3987/COM-06-S(O)23, 69, 1, 91-98, 2006.12, The synthesis of the CDEF ring fragment of yessotoxin, a marine ladder polyether, has been achieved. Union of three components, the C ring aldehyde, the F ring diol, and trimethylsilyl cyanide, was accomplished by treatment with Sc(OTf)
3
to afford the α-cyano ether both in stepwise and one-pot reactions. The DE ring system was constructed through a ring closing metathesis reaction and reductive etherification sequence..
59. Kohei Torikai, Hiroshi Yari, Megumi Mori, Satoru Ujihara, Nobuaki Matsumori, Michio Murata, Tohru Oishi, Design and synthesis of an artificial ladder-shaped polyether that interacts with glycophorin A, Bioorganic and Medicinal Chemistry Letters, 10.1016/j.bmcl.2006.09.004, 16, 24, 6355-6359, 2006.12, Ladder-shaped polyether (LSP) compounds, such as brevetoxins and ciguatoxins, are thought to interact with transmembrane (TM) proteins. As a model LSP compound, we designed and synthesized an artificial tetracyclic ether (1) and evaluated its interaction with glycophorin A (GpA), a membrane protein known to dimerize or oligomerize between membrane-integral α-helical domains. Model compound 1 was found to induce the dissociation of oligomeric GpA in a similar manner to natural LSPs when examined by SDS-PAGE. The results suggest that even an artificial tetracyclic ether possesses the ability to interact with TM proteins, presumably through the intermolecular hydrogen bonds (Cα-H ⋯ O) with the GXXXG motif..
60. Kohei Torikai, Hiroshi Yari, Michio Murata, Tohru Oishi, Synthesis of artificial ladder-shaped polyethers containing a 6/7 cis-fused ring system, Heterocycles, 70, 161-167, 2006.12, Ladder-shaped tetracyclic and heptacyclic ethers containing a 6/7 cis-fused ring system have been synthesized. The synthesis features convergent coupling of monocyclic building blocks through esterification, ring-closing reaction using a low-valent titanium complex, and hydroxy dithioacetal cyclization. The double reaction strategy enabled expeditious synthesis of the heptacyclic ether in only thirteen steps from the building blocks..
61. Masakazu Sugishima, Yuichiro Higashimoto, Tohru Oishi, Hidenori Takahashi, Hiroshi Sakamoto, Masato Noguchi, Keiichi Fukuyama, X-ray crystallographic and biochemical characterization of the inhibitory action of an imidazole-dioxolane compound on heme oxygenase, Biochemistry, 10.1021/bi062264p, 46, 7, 1860-1867, 2007.02, Heme oxygenase (HO) catalyzes the regiospecific cleavage of the porphyrin ring of heme using reducing equivalents and O2 to produce biliverdin, iron, and CO. Because CO has a cytoprotective effect through the p38-MAPK pathway, HO is a potential therapeutic target in cancer. In fact, inhibition of the HO isoform HO-1 reduces Kaposi sarcoma tumor growth. Imidazole-dioxolane compounds have recently attracted attention because they have been reported to specifically inhibit HO-1, but not HO-2, unlike Cr-containing protoporphyrin IX, a classical inhibitor of HO, that inhibits not only both HO isoforms but also other hemoproteins. The inhibitory mechanism of imidazole-dioxolane compounds, however, has not yet been characterized. Here, we determine the crystal structure of the ternary complex of rat HO-1, heme, and an imidazole-dioxolane compound, 2-[2-(4-chlorophenyl)ethyl]-2-[(1H-imidazol-1-yl)methyl]-1,3- dioxolane. This compound bound on the distal side of the heme iron, where the imidazole and 4-chlorophenyl groups were bound to the heme iron and the hydrophobic cavity in HO, respectively. Binding of the bulky inhibitor in the narrow distal pocket shifted the distal helix to open the distal site and moved both the heme and the proximal helix. Furthermore, the biochemical characterization revealed that the catalytic reactions of both HO-1 and HO-2 were completely stopped after the formation of verdoheme in the presence of the imidazole-dioxolane compound. This result should be mainly due to the lower reactivity of the inhibitor-bound verdoheme with O2 compared to the reactivity of the inhibitor-bound heme with O2..
62. Koji Watanabe, Hiroaki Minato, Michio Murata, Tohru Oishi, Synthesis of the JK ring fragments of yessotoxin and 42,43,44,45,46,47,55-heptanor-41-oxoyessotoxin, Heterocycles, 72, 207-212, 2007.04, The JK ring fragment (7) of 42,43,44,45,46,47,55-heptanor-41-oxoyessotoxin was synthesized via enyne metathesis and 6-exo cyclization of a hydroxy epoxide. Conversion of 7 into the JK ring fragment (6) of yessotoxin was achieved in a single step by treatment with an alkenyllithium..
63. Yuichi Umegawa, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Amphotericin B covalent dimers with carbonyl-amino linkage
a new probe for investigating ion channel assemblies, Tetrahedron Letters, 10.1016/j.tetlet.2007.03.058, 48, 19, 3393-3396, 2007.05, Based on an amphotericin B (AmB) ion-channel model where the close proximity of neighboring molecules is effected by interaction between carboxyl and amino groups, we prepared covalent dimers of AmB connected between these functionalities. While directly connected and short-tethered derivatives (2 and 3) lacked the activities, dimer 4 with a longer linker revealed K+ ion flux activity, suggesting that some distance and/or flexibility between the carboxyl and amino groups in adjacent molecules is required for the formation of ion-permeable complex in biomembranes..
64. Eri Kondoh, Aru Konno, Kazuo Inaba, Tohru Oishi, Michio Murata, Manabu Yoshida, Valosin-Containing Protein/p97 Interacts with Sperm-Activating and Sperm-Attracting Factor (SAAF) in the Ascidian Egg and Modulates Sperm-Attracting Activity., Dev. Growth Differ., 50, 665-673, 2008.01.
65. Kohei Torikai, Koji Watanabe, Hiroaki Minato, Tomoyoshi Imaizumi, Michio Murata, Tohru Oishi, Convergent Synthesis of the A-J Ring System of Yessotoxin., Synlett, 2368-2372, 2008.01.
66. Manabu Yoshida, Kogiku Shiba, Kaoru Yoshida, Hiroshi Tsuchikawa, Ouichirou Ootou, Tohru Oishi, Michio Murata, Ascidian Sperm Activating and Attracting Factor: Importance of Sulfate Groups for the Activities and Implication of Its Putative Receptor., FEBS Lett., 582, 3429-3433, 2008.01.
67. Nagy Morsy, Keiichi Konoki, Toshihiro Houdai, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Saburo Aimoto, Roles of Integral Protein in Membrane Permeabilization by Amphidinols., Biochim. Biophys. Acta, Biomembranes, 1778, 1453-1459, 2008.01.
68. Nagy Morsy, Toshihiro Houdai, Keiichi Konoki, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Effects of Lipid Constituents on Membrane-Permeabilizing Activity of Amphidinols., Bioorg. Med. Chem., 16, 3084-3090, 2008.01.
69. Nobuaki Matsumori, Yusuke Kasai, Tohru Oishi, Michio Murata, Kaoru Nomura, Orientation of Fluorinated Cholesterol in Lipid Bilayers Analyzed by 19F Tensor Calculation and Solid-State NMR., J. Am. Chem. Soc., 130, 4757-4766, 2008.01.
70. Ryota Mouri, Keiichi Konoki, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Complex Formation of Amphotericin B in Sterol-Containing Membranes As Evidenced by Surface Plasmon Resonance., Biochemistry, 47, 7807-7815, 2008.01.
71. Satoru Ujihara, Tohru Oishi, Kohei Torikai, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Yasukatsu Oshima, Saburo Aimoto, Interaction of Ladder-Shaped Polyethers with Transmembrane -Helix of Glycophorin A as Evidenced by Saturation Transfer Difference NMR and Surface Plasmon Resonance. , Bioorg. Med. Chem. Lett., 18, 6115-6118, 2008.01.
72. Tohru Oishi, Futoshi Hasegawa, Kohei Torikai, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Convergent Synthesis and Biological Activity of the WXYZA’B’C’ Ring System of Maitotoxin. Tohru Oishi, Futoshi Hasegawa, Kohei Torikai, Keiichi Konoki, Nobuaki Matsumori, Michio Murata Org. Lett. 2008, 10, 3599-3602., Org. Lett., 10, 3599-3602, 2008.01.
73. Tohru Oishi, Mitsunori Kanemoto, Respati Swasono, Nobuaki Matsumori, Michio Murata, Combinatorial Synthesis of the 1,5-Polyol System Based on Cross Metathesis: Structure Revision of Amphidinol 3., Org. Lett., 10, 5203-5206, 2008.01.
74. Yuichi Umegawa, Nobuaki Matsumori, Tohru Oishi, Michio Murata., Ergosterol Increases the Intermolecular Distance of Amphotericin B in the Membrane-Bound Assembly As Evidenced by Solid-State NMR., Biochemistry, 47, 13463-13469, 2008.01.
75. Yusuke Kasai, Nobuaki Matsumori, Yuichi Umegawa, Shigeru Matsuoka, Hiroyuki Ueno, Hiroki Ikeuchi, Tohru Oishi, Michio Murata, Self-Assembled Amphotericin B is Probably Surrounded by Ergosterol: Bimolecular Interactions as Evidenced by Solid-State NMR and CD Spectra., Chem. Eur. J., 14, 1178-1185, 2008.01.
76. Yusuke Kasai, Nobuaki Matsumori, Yuichi Umegawa, Shigeru Matsuoka, Hiroyuki Ueno, Hiroki Ikeuchi, Tohru Oishi, Michio Murata, Self-assembled amphotericin B is probably surrounded by ergosterol
Bimolecular interactions as evidenced by solid-state NMR and CD spectra, Chemistry - A European Journal, 10.1002/chem.200701256, 14, 4, 1178-1185, 2008.02, Amphotericin B (AmB) is thought to exert its pharmacological effects by forming a barrel-stave assembly with ergosterol in fungal membranes. To examine the interaction between AmB and ergosterol (Erg) or cholesterol (Cho), 13C- and 19F-labelled covalent conjugales were prepared as reported previously (N. Matsumori et al. Chem. Biol. 2004, 11, 673-679). The CD spectra of the conjugates in a membrane-bound form suggested that the distance between the heptaene moieties of the ergosterol conjugates AmB-C 2-(6-F)Erg 2 and AmB-C2Erg 3 is similar to that of AmB in ergosterol-containing membranes, but significantly larger than that of AmB in nonsterol or cholesterol-containing mem branes. These observations suggest that, as is the case with ergosterol-containing membranes, the conjugated sterol moiety prevents the close contact between the heptaene moieties within the membrane that would reduce channel conductivity of the AmB assemblies. To further investigate this bimolecular interaction, we recorded the solid-state NMR spectra of conjugates 2 and AmB-C2-(6-F)Cho 4. which are composed of uniformly 13C-labelled AmB and 6-fluorinuted ergosterol or cholesterol; the conjugates were expected to facilitate the estimation of distances between the fluorine and carbon atoms. By using rotor-synchronous double resonance (rotational echo double resonance of X cluster; RDX) experiments, we deduced the distance between the fluorine atom and its nearest carbon atom in the heptaene moiety of 2 to be less than 8.6 Å. This indicates that the B ring of ergosterol comes close to the AmB polyene moiety. A conformational search of the AmB-ergosterol conjugate by using distance constraints derived from the RDX results suggested that ergosterol molecules possibly surround the AmB assembly, which is in contrast with the conventional image in which ergosterol is inserted into AmB molecules..
77. Nagy Morsy, Toshihiro Houdai, Keiichi Konoki, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Effects of lipid constituents on membrane-permeabilizing activity of amphidinols, Bioorganic and Medicinal Chemistry, 10.1016/j.bmc.2007.12.029, 16, 6, 3084-3090, 2008.03, Amphidinols (AMs) are a new class of polyhydroxyl polyene compounds with potent antifungal activity. Membrane-permeabilizing activities of AM2, AM3, and AM6 were examined using fluorescent-dye leakage experiments with various phosphatidylcholines (PCs) and sterols. All the AMs tested showed the potent activity to cholesterol-containing liposomes. In the absence of the sterol, AM2, AM3, and AM6 had no membrane-permeabilizing activities to membranes of saturated PC. In liposomes consisting of unsaturated PC, AM2, which possesses an additional ether ring in a polyhydroxyl chain, showed membrane-permeabilizing activities with a moderate efficacy, while AM3 or AM6 did not. The potentiation by sterols was prominent even at 0.5% (wt/wt) and structure-dependent, which ruled out the possibility that alteration of the membrane physical properties induced by sterol was chiefly responsible for this sterol effect. The finding that their activity was not affected by membrane thickness implies that AMs permeabilized membrane by a different mechanism from that of polyene macrolide antibiotics..
78. Nobuaki Matsumori, Yusuke Kasai, Tohru Oishi, Michio Murata, Kaoru Nomura, Orientation of fluorinated cholesterol in lipid bilayers analyzed by 19F tensor calculation and solid-state NMR, Journal of the American Chemical Society, 10.1021/ja077580l, 130, 14, 4757-4766, 2008.04, 6-F-cholesterol was reported to exhibit biological and interfacial properties similar to unmodified cholesterol. We have also found that 6-F-cholesterol mimicked the cholesterol activity observed in the systems of amphotericin B and lipid rafts. However, to use 6-F-cholesterol as a molecular probe to explore molecular recognition in membranes, it is indispensable to have detailed knowledge of the dynamic and orientation properties of the molecule in membrane environments. In this paper, we present the molecular orientation of 6-F-cholesterol (30 mol %) in dimyristoylphosphatidylcholine (DMPC) bilayers revealed by combined use of 19F chemical shift anisotropy (CSA), 2H NMR, and C-F rotational echo double resonance (REDOR) experiments. The axis of rotation of 6-F-cholesterol was shown to be in a similar direction to that of cholesterol in DMPC bilayers, which is almost parallel to the long axis of the molecular frame. The molecular order parameter of 6-F-cholesterol was determined to be ca. 0.85, which is within the range of reported values of cholesterol. These findings suggest that the dynamic properties of 6-F-cholesterol in DMPC are quite similar to those of unmodified cholesterol; therefore, the introduction of a fluorine atom at C6 has virtually no effect on cholesterol dynamics in membranes. In addition, this study demonstrates the practical utility of theoretical calculations for determining the 19F CSA principal axes, which would be extremely difficult to obtain experimentally. The combined use of quantum calculations and solid-state 19F NMR will make it possible to apply the orientation information of 19F CSA tensors to membrane systems..
79. Nagy Morsy, Keiichi Konoki, Toshihiro Houdai, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Saburo Aimoto, Roles of integral protein in membrane permeabilization by amphidinols, Biochimica et Biophysica Acta - Biomembranes, 10.1016/j.bbamem.2008.01.018, 1778, 6, 1453-1459, 2008.06, Amphidinols (AMs) are a group of dinoflagellate metabolites with potent antifungal activity. As is the case with polyene macrolide antibiotics, the mode of action of AMs is accounted for by direct interaction with lipid bilayers, which leads to formation of pores or lesions in biomembranes. However, it was revealed that AMs induce hemolysis with significantly lower concentrations than those necessary to permeabilize artificial liposomes, suggesting that a certain factor(s) in erythrocyte membrane potentiates AM activity. Glycophorin A (GpA), a major erythrocyte protein, was chosen as a model protein to investigate interaction between peptides and AMs such as AM2, AM3 and AM6 by using SDS-PAGE, surface plasmon resonance, and fluorescent-dye leakages from GpA-reconstituted liposomes. The results unambiguously demonstrated that AMs have an affinity to the transmembrane domain of GpA, and their membrane-permeabilizing activity is significantly potentiated by GpA. Surface plasmon resonance experiments revealed that their interaction has a dissociation constant of the order of 10 μM, which is significantly larger than efficacious concentrations of hemolysis by AMs. These results imply that the potentiation action by GpA or membrane integral peptides may be due to a higher affinity of AMs to protein-containing membranes than that to pure lipid bilayers..
80. Ryota Mouri, Keiichi Konoki, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Complex formation of amphotericin B in sterol-containing membranes as evidenced by surface plasmon resonance, Biochemistry, 10.1021/bi800334p, 47, 30, 7807-7815, 2008.07, Amphotericin B (AmB) is a membrane-active antibiotic that increases the permeability of fungal membranes. Thus, the dynamic process of its interaction with membranes poses intriguing questions, which prompted us to elaborate a quick and reliable method for real-time observation of the drug's binding to phospholipid liposomes. We focused on surface plasmon resonance (SPR) and devised a new modification method of sensor chips, which led to a significant reduction in the level of nonspecific binding of the drug in a control lane. With this method in hand, we examined the affinity of AmB for various membrane preparations. As expected, AmB exhibited much higher affinity for sterol-containing palmitoyloleoylphosphatidylcholine membranes than those without sterol. The sensorgrams recorded under various conditions partly fitted theoretical curves, which were based on three interaction models. Among those, a two-state reaction model reproduced well the sensorgram of AmB binding to an ergosterol-containing membrane; in this model, two states of membrane-bound complexes, AB and AB*, are assumed, which correspond to a simple binding to the surface of the membrane (AB) and formation of another assembly in the membrane (AB*) such as an ion channel complex. Kinetic analysis demonstrated that the association constant in ergosterol-containing POPC liposomes is larger by 1 order of magnitude than that in the cholesterol-containing counterpart. These findings support the previous notion that ergosterol stabilizes the membrane-bound assembly of AmB..
81. Kohei Torikai, Tohru Oishi, Satoru Ujihara, Nobuaki Matsumori, Keiichi Konoki, Michio Murata, Saburo Aimoto, Design and synthesis of ladder-shaped tetracyclic, heptacyclic, and decacyclic ethers and evaluation of the interaction with transmembrane proteins, Journal of the American Chemical Society, 10.1021/ja801576v, 130, 31, 10217-10226, 2008.08, Ladder-shaped polyether (LSP) toxins represented by brevetoxins and Ciguatoxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, we have synthesized artificial ladder-shaped polyethers (ALPs) containing 6/7/6/6 tetracyclic, 6/7/6/6/7/6/6 heptacyclic, and 6/7/6/6/7/6/6/7/6/6 decacyclic systems, based on the convergent method via α-cyano ethers. The ALPs possessing the simple iterative structure with different numbers of rings would be useful for structure-activity relationship studies on the molecular length, which is supposed to be important when naturally occurring LSPs elicit their toxicity. Two series of ALPs were prepared to evaluate the hydrophilic or hydrophobic effects of the side chains: (i) both sides were functionalized as diols (A series), and (ii) one side remained as diol and the other side was protected as benzyl ethers (B series). To examine the interaction of these ALPs with TM proteins, dissociation of glycophorin A (GpA) dimers into monomers was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The heptacyclic ether (ALP7B) elicited the most potent activity in the presence of 2% SDS buffer, whereas the decacyclic ether (ALP10A) exhibited an intriguing phenomenon to induce precipitation of GpA in a dose-dependent manner, under the low concentration of SDS (0.03%). ALP10A also induced precipitation of integrin α 1β1, a TM protein known to form heterodimers in the lipid bilayer membranes. The different activities among the ALPs can be accounted for by the concept of "hydrophobic matching" that is, lengths of the hydrophobic region including the side chains of ALP7B and ALP10A are ca. 25 Å, which match the lengths of the hydrophobic region of α-helical TM proteins, as well as the hydrophobic thickness of lipid bilayer membranes. The concept of the hydrophobic matching would be a clue to understanding the interaction between LSPs and TM proteins, and also a guiding principle to design ALPs possessing potent affinities with TM proteins..
82. Kohei Torikai, Koji Watanabe, Hiroaki Minato, Tomoyoshi Imaizumi, Michio Murata, Tohru Oishi, Convergent synthesis of the A-J ring system of yessotoxin, Synlett, 10.1055/s-2008-1078266, 15, 2368-2372, 2008.09, A highly convergent synthesis of the A-J ring system of yessotoxin was achieved. A convergent strategy via α-cyano ethers was extensively applied in the assembly of the F and IJ ring fragments to afford the FGHIJ ring unit, followed by coupling with the ABC ring unit..
83. Manabu Yoshida, Kogiku Shiba, Kaoru Yoshida, Hiroshi Tsuchikawa, Ouichirou Ootou, Tohru Oishi, Michio Murata, Ascidian sperm activating and attracting factor
Importance of sulfate groups for the activities and implication of its putative receptor, FEBS Letters, 10.1016/j.febslet.2008.09.006, 582, 23-24, 3429-3433, 2008.10, The sperm activating and attracting factor (SAAF) from the eggs of the ascidian Ciona intestinalis was identified as the sulfated polyhydroxysterol,3α,4β,7α,26-tetrahydroxy-5α-cholestane-3,26-disulfate. We present a functional analysis of SAAF derivatives that reveals the roles of the various SAAF functional groups. Optical isomerism does not affect SAAF activities. Hydrolysis on one side, i.e. at the sulfate groups of SAAF, decreases the sperm-activating and sperm-attracting activities, while hydrolysis on both sides resulted in the loss of both activities. Biotinylated-SAAF lost its sperm-activating ability, but retained sperm-binding and chemotactic abilities. Thus, the sulfate groups of SAAF are responsible for these activities..
84. Eri Kondoh, Aru Konno, Kazuo Inaba, Tohru Oishi, Michio Murata, Manabu Yoshida, Valosin-containing protein/p97 interacts with sperm-activating and sperm-attracting factor (SAAF) in the ascidian egg and modulates sperm-attracting activity, Development Growth and Differentiation, 10.1111/j.1440-169X.2008.01064.x, 50, 8, 665-673, 2008.10, Sperm chemotaxis toward an egg is observed in many animals, and the control of sperm-attracting activity is thought to play an important role in ensuring fertilization. However, the mechanism underlying the release of a sperm attractant from an egg is still obscure. In this study, we examined the systems involved in the release of sperm-activating and sperm-attracting factor (SAAF), which is the sperm attractant of the ascidian Ciona intestinalis. Here, we show that the egg acquires sperm-attracting activity after germinal vesicle breakdown. Further, since the cytoplasmic extracts of immature oocytes exhibit no sperm-attracting activity, the SAAF in oocytes may be activated after germinal vesicle breakdown. We found 13 SAAF-binding proteins in an egg plasma membrane extract and identified five proteins by proteomic analysis: valosin-containing protein (VCP)/p97, proteasome alpha 2 subunit, MGC97756 protein, proteasome subunit Y, and beta-tubulin. In particular, the interaction between VCP/p97 and SAAF was confirmed by a pull-down assay. VCP/p97 is initially localized in the germinal vesicle, and during oocyte maturation, it shifts to the endoplasmic reticulum in the cortical regions. Thus, VCP/p97 is a potential modulator of SAAF release from the egg..
85. Tohru Oishi, Mitsunori Kanemoto, Respati Swasono, Nobuaki Matsumori, Michio Murata, Combinatorial synthesis of the 1,5-polyol system based on cross metathesis
Structure revision of amphidinol 3, Organic Letters, 10.1021/ol802168r, 10, 22, 5203-5206, 2008.12, (Chemical Equation Presented) Combinatorial synthesis of a 1,5-polyol system corresponding to the C1-C14 unit of amphidinol 3 (AM3) and its diastereomers was achieved via chemoselective cross metathesis as the key step. Comparison of 13C NMR data of the synthetic specimens with that of AM3 led to a controversy regarding the originally proposed structure. From GC-MS analysis of the degradation product, the absolute configuration at C2 of AM3 has been revised to be R..
86. Tohru Oishi, Futoshi Hasegawa, Kohei Torikai, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Convergent synthesis and biological activity of the WXYZA′B′ C′ ring system of maitotoxin, Organic Letters, 10.1021/ol801369g, 10, 16, 3599-3602, 2008.12, (Chemical Equation Presented) The WXYZA′B′C′ ring system (1) of maitotoxin (MTX) was synthesized in a convergent manner via successive coupling of the W, Z, and C′ ring fragments through construction of the XY and A′B′ ring systems. The synthetic segment 1 blocked the hemolytic activity elicited by MTX..
87. Yuichi Umegawa, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Ergosterol increases the intermolecular distance of amphotericin B in the membrane-bound assembly as evidenced by solid-state NMR, Biochemistry, 10.1021/bi801875y, 47, 51, 13463-13469, 2008.12, Amphotericin B (AmB) exerts its antifungal activity by forming ion-permeable assemblies across lipid bilayers. To investigate AmB-AmB bimolecular interactions in the assembly, we carried out 13C{ 19F}REDOR experiments using 14-19F- and 13C41-labeled AmBs in sterol-containing and sterol-free palmitoyloleoylphosphatidylcholine (POPC) membranes and measured the average distance between the labeled sites of AmBs in membrane-bound forms. The REDOR results suggested that the intermolecular distance of AmB molecules is significantly increased in the ergosterol membrane as compared with the cholesterol membrane. This sterol-dependent change was supported by the UV spectra of AmB in lipid bilayers, in which the excitonic absorption band arising from the aggregated state of AmB shifted to longer wavelength in ergosterol-containing POPC membrane. The REDOR experiments also disclosed that the head-to-head orientation of AmB is predominant in both of the sterol-containing membranes and AmB-POPC interaction was detected only in the ergosterol membrane. Ergosterol significantly influences the interactions between AmB molecules as well as those between AmB and POPC, which may facilitate formation of ion-permeable channels in ergosterol-containing membrane..
88. Satoru Ujihara, Tohru Oishi, Kohei Torikai, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Yasukatsu Oshima, Saburo Aimoto, Interaction of ladder-shaped polyethers with transmembrane α-helix of glycophorin A as evidenced by saturation transfer difference NMR and surface plasmon resonance, Bioorganic and Medicinal Chemistry Letters, 10.1016/j.bmcl.2008.10.020, 18, 23, 6115-6118, 2008.12, Ladder-shaped polyether (LSP) compounds are thought to interact with transmembrane α-helices, but direct evidence has scarcely obtained for these interactions. We adopted a transmembrane α-helix of glycophorin A, and quantitatively evaluated its interaction with LSPs such as yessotoxin (YTX), desulfated YTX and artificial LSPs, using surface plasmon resonance and saturation transfer difference NMR. As a result, dissociation constants (KD) of YTX and desulfated YTX to a transmembrane domain peptide of glycophorin A were determined to be in the submillimolar range. Furthermore, in saturation transfer difference NMR, the signals at the polyene side chain and the angular methyl groups of YTX were significantly attenuated, which probably comprised an interacting interface of LSPs with a transmembrane α-helix. These results suggest that hydrophobic interaction plays an important role in molecular recognition of the α-helix peptide by LSPs..
89. Michio Murata, Nobuaki Matsumori, Keiichi Konoki, Tohru Oishi, Structural features of dinoflagellate toxins underlying biological activity as viewed by NMR, Bulletin of the Chemical Society of Japan, 10.1246/bcsj.81.307, 81, 3, 307-319, 2008.12, Marine dinoflagellates are a rich source of structurally and biologically intriguing secondary metabolites. Among those, maitotoxin may be one of the best known examples, which is the largest natural product known to date and possesses the most potent toxicity known amongst non-proteinaceous compounds. Structural studies of maitotoxin are reviewed with a particular focus on the configuration and mode of action of this unique toxin. In addition, there are many marine natural products which bind to biomembranes to exert their biological activities. To gain a better understanding of their mode of action, conformation, and bimoleeular interaction occurring in biomembranes are particularly important. Recent results from NMR studies of membrane systems in the authors' group are reviewed briefly..
90. Naohiro Matsushita, Yukiko Matsuo, Hiroshi Tsuchikawa, Nobuaki Matsumori, Michio Murata, Tohru Oishi, Synthesis of 25- 13c-amphotericin B methyl ester
A molecular probe for solid-state NMR measurements, Chemistry Letters, 10.1246/cl.2009.114, 38, 2, 114-115, 2009, A 13C-labeled amphotericin B (AmB) derivative was synthesized based on a hybrid strategy combining chemical synthesis with degradation of a natural product through successive cross-coupling reactions and macrolactonization. The specimen regiospecifically 13C-labeled (99% enrichment) at C25 position corresponding to the polyene moiety would be a powerful tool for structural analysis of the molecular assembly formed by AmB based on solid-state NMR measurements..
91. Keiichi Konoki, Masaki Hashimoto, Kaori Honda, Kazuo Tachibana, Rie Tamate, Futoshi Hasegawa, Tohru Oishi, Michio Murata, Maitotoxin-Photoactive Probe Binds to Membrane Proteins in Blood Cells., Heterocycles, 79, 1007-1017, 2009.01.
92. Keisuke Maruyoshi, Kaori Nonaka, Takeshi Sagane, Tetsuo Demura, Toshiyuki Yamaguchi, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Conformational Change of Spermidine upon Interaction with Adenosine Triphosphate in Aqueous Solution., Chem. Eur. J., 15, 1618-1626, 2009.01.
93. Michio Murata, Yusuke Kasai, Yuichi Umegawa, Naohiro Matsushita, Hiroshi Tsuchikawa, Nobuaki Matsumori, Tohru Oishi, Ion Channel Complex of Antibiotics as Viewed by NMR., Pure Appl. Chem., 81, 1123–1129, 2009.01.
94. Mitsunori Kanemoto, Michio Murata, Tohru Oishi, Stereoselective Synthesis of the C31-C40/C43-C52 Unit of Amphidinol 3, J. Org. Chem., 74, 8810–8813, 2009.01.
95. Naohiro Matsushita, Yukiko Matsuo, Hiroshi Tsuchikawa, Nobuaki Matsumori, Michio Murata, Tohru Oishi, Synthesis of 25-13C-Amphotericin B Methyl Ester: A Molecular Probe for Solid-state NMR Measurements., Chem. Lett., 38, 114-115, 2009.01.
96. Nobuaki Matsumori, Kazuaki Tahara, Hiroko Yamamoto, Atsushi Morooka, Mototsugu Doi, Tohru Oishi, Michio Murata, Direct Interaction between Amphotericin B and Ergosterol in Lipid Bilayers As Revealed by 2H NMR Spectroscopy., J. Am. Chem. Soc., 131, 11855–11860, 2009.01.
97. Ryota Mouri, Tohru Oishi, Kohei Torikai, Satoru Ujihara, Nobuaki Matsumori, Michio Murata, Yasukatsu Oshima, Surface Plasmon Resonance-Based Detection of Ladder-Shaped Polyethers by Inhibition Detection Method., Bioorg. Med. Chem. Lett., 19, 2824-2828, 2009.01.
98. Keisuke Maruyoshi, Kaori Nonaka, Takeshi Sagane, Tetsuo Demura, Toshiyuki Yamaguchi, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Conformational change of spermidine upon interaction with adenosine triphosphate in aqueous solution, Chemistry - A European Journal, 10.1002/chem.200801961, 15, 7, 1618-1626, 2009.02, Endogenous polyamines, represented by putrescine, spermidine, and spermine, are known to exert their physiological functions by interacting with polyanionic biomolecules such as DNA, RNA, adenosine triphosphate (ATP), and phospholipids. Very few examples of conformation analysis have been reported for these highly flexible polymethylene compounds, mainly due to the lack of appropriate methodologies. To understand the molecular basis of the weak interaction between polyamines and polyanions that underlies their physiological functions, we aimed to elucidate the solution conformation of spermidine by using diastereospecifically deuterated and
13
C-labeled derivatives (1-7), which were designed to diagnose the orientation of seven conformationally relevant bonds in spermidine. 1H-1H and
13
C-1H NMR coupling constants (
3
J
H,H
and
3
J
C,H
) were successfully determined for a spermidine-ATP complex. The relevant coupling constants markedly decreased upon complexation. The results reveal that spermidine, when interacting with ATP, undergoes changes that make the conformation more bent and forms the complex with the triphosphate part of ATP in an orientation-sensitive manner..
99. Yoshinori Sugimoto, Keiichi Konoki, Michio Murata, Masafumi Matsushita, Hiroshi Kanazawa, Tohru Oishi, Design, synthesis, and biological evaluation of fluorinated analogues of salicylihalamide, Journal of Medicinal Chemistry, 10.1021/jm801265e, 52, 3, 798-806, 2009.02, Salicylihalamide A (SA), a benzolactone enamide compound, possesses potent cytotoxicity against human tumor cell lines. SA is a selective inhibitor of mammalian vacuolar type H+-ATPase (V-ATPase), and is distinct from previously known V-ATPase inhibitors such as bafilomycins and concanamycins that do not discriminate between mammalian and nonmammalian V-ATPases. Because of its potent antitumor activity and structural simplicity, SA is a promising candidate for an anticancer drug. Although a number of structure-activity relation studies using synthetic analogues have been reported, no fluorinated derivative of SA has been evaluated even though selective addition of a fluorine atom into a therapeutic small molecule candidate often enhances pharmacokinetic and physicochemical properties. We designed and synthesized fluorinated analogues of SA and evaluated their V-ATPase inhibitory activities. Compared to the natural product, the synthetic analogues were potent V-ATPase inhibitors, suggesting that these analogues are potential drug candidates and potential molecular probes for mode-of-action studies using fluorine-based analytical methods such as 19F-NMR spectroscopy..
100. Ryota Mouri, Tohru Oishi, Kohei Torikai, Satoru Ujihara, Nobuaki Matsumori, Michio Murata, Yasukatsu Oshima, Surface plasmon resonance-based detection of ladder-shaped polyethers by inhibition detection method, Bioorganic and Medicinal Chemistry Letters, 10.1016/j.bmcl.2009.03.103, 19, 10, 2824-2828, 2009.05, Ladder-shaped polyether (LSP) compounds represented by brevetoxins and ciguatoxins were largely discovered in association with seafood poisoning. Thus, a quick quantification method for LSPs is potentially important. We examined a surface plasmon resonance method using desulfated-yessotoxin (dsYTX) immobilized on a sensor chip and phosphodiesterase PDEII in a inhibition detection mode. Yessotoxin, brevetoxin B and synthetic LSP derivatives showed clear inhibition against PDEII binding to the immobilized dsYTX, by which their half inhibitory concentrations were successfully estimated. This inhibition method appeared to be superior in specificity to direct binding assays where binding proteins to LSP was immobilized on a sensor chip..
101. Michio Murata, Yusuke Kasai, Yuichi Umegawa, Naohiro Matsushita, Hiroshi Tsuchikawa, Nobuaki Matsumori, Tohru Oishi, Ion channel complex of antibiotics as viewed by NMR, Pure and Applied Chemistry, 10.1351/PAC-CON-08-08-37, 81, 6, 1123-1129, 2009.07, Amphotericin B (AmB) exerts its pharmacological effects by forming a barrel-stave assembly in fungal membranes. To examine the interaction between AmB and ergosterol or cholesterol, 13C- and 19F-labeled covalent conjugates were prepared and subjected to solidstate NMR measurements. Using rotor-synchronous double-resonance experiments such as rotational echo double resonance (REDOR) and RDX, we estimated the distance between the fluorine atom and its nearest carbon in the heptaene moiety to be less than 8.6 A ̊, indicating that the B ring of ergosterol comes close to the AmB polyene moiety. Conformational search of the AmB-ergosterol conjugate using the NMR-derived constraints suggested that ergosterol molecules surround the AmB assembly in contrast to the conventional image where ergosterol is inserted into AmB molecules. AmB-AmB bimolecular interaction was examined by using 13C- and 19F-labeled AmBs in dimyritoylphosphatidylcholine (DMPC) membrane without sterols. 13C- and 19F dipolar interactions deriving from both head-to-head and head-to-tail orientations were observed in the REDOR experiments. The interactions between AmB and acyl chains of the phospholipid were also detected..
102. Keiichi Konoki, Masaki Hashimoto, Kaori Honda, Kazuo Tachibana, Rie Tamate, Futoshi Hasegawa, Tohru Oishi, Michio Murata, Maitotoxin-photoactive probe binds to membrane proteins in blood cells, Heterocycles, 10.3987/COM-08-S(D)78, 79, C, 1007-1017, 2009.07, The photoactive and biotinylating ligand was prepared from MTX and maleimide-conjugated Hatanaka reagent with use of Diels-Alder reaction. Blood cells were subjected to affinity labelling experiments using the ligand thus obtained. The labelled band on SDS-PAGE was replaced not by MTX but by brevetoxin B (PbTx2), which suggested the presence of binding proteins in blood 2+ cells. Screening of polyether compounds for MTX inhibitory activity using Ca flux assays in C6 cells disclosed that a synthetic fragment of the hydrophilic portion of MTX inhibited the MTX activity..
103. Nobuaki Matsumori, Kazuaki Tahara, Hiroko Yamamoto, Atsushi Morooka, Mototsugu Doi, Tohru Oishi, Michio Murata, Direct interaction between amphotericin B and ergosterol in lipid bilayers as revealed by 2H NMR spectroscopy, Journal of the American Chemical Society, 10.1021/ja9033473, 131, 33, 11855-11860, 2009.08, Although amphotericin B (AmB) is thought to exert its antifungal activity by forming transmembrane ion-permeable self-assemblies together with ergosterol, no previous study has directly proven AmB-ergosterol interaction. To establish the interaction, we measured 2H NMR using deuterium-labeled sterols and AmB. The 2H NMR spectra of deuterated ergosterol in palmitoyloleoylphosphatidylcholine (POPC) bilayers showed that fast axial diffusion of erogosterol was almost completely inhibited by the coexistence of AmB. Conversely, cholesterol mobility in POPC membrane was essentially unchanged with or without AmB. These results unequivocally demonstrate that ergosterol has significant interaction with AmB in POPC bilayers. In addition, we examined the mobility of AmB using deuterium-labeled AmB, and found that, although AmB is almost immobilized in sterol-free and cholesterol-containing POPC membranes, a certain ratio of AmB molecules acquires mobility in the presence of ergosterol. The similar mobility of AmB and ergosterol in POPC bilayers confirmed the idea of the direct intermolecular interaction between ergosterol and AmB..
104. Mitsunori Kanemoto, Michio Murata, Tohru Oishi, Stereoselective synthesis of the C31-C40/C43-C52 unit of amphidinol 3, Journal of Organic Chemistry, 10.1021/jo901793f, 74, 22, 8810-8813, 2009.11, (Chemical Equation Presented) A concise synthesis of a tetrahydropyran ring system corresponding to the C31-C40 and C43-C52 units of amphidinol 3 is described. Successive chemoselective reactions, i.e., cross-metathesis to differentiate the iodoolefin from the terminal olefin and Sharpless asymmetric dihydroxylation on the resulting E-olefin, resulted in expeditious synthesis of an intermediate that was then cross-coupled to afford an E,E-diene system. Four contiguous stereogenic centers were installed via construction of the tetrahydropyran ring by means of Katsuki-Sharpless asymmetric epoxidation, 6-endo-tet cyclization, and Sharpless asymmetric dihydroxylation..
105. Tohru Oishi, Kohei Torikai, Futoshi Hasegawa, Design and synthesis of ladder-shaped polyethers and evaluation of the interaction with transmembrane proteins, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.67.1250, 67, 12, 1250-1260, 2009.12, Ladder-shaped polyether (LSP) toxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, artificial ladder-shaped polyethers (ALPs) possessing simple iterative structure with different number of rings were synthesized based on the convergent method via α-cyano ethers. The interaction of these ALPs with TM proteins was evaluated, and we found that the difference of activities among the ALPs can be accounted for by the concept of "hydrophobic matching" i. e. lengths of the hydrophobic region including the side chains of ALPs are ca. 25 Å, which match the lengths of the hydrophobic region of α-helical TM proteins. The partial structure corresponding to the WXYZA'B'C' ring system of maitotoxin (MTX) was synthesized based on the convergent method via α-cyano ethers, and we found that hemolysis of human red blood cells induced by MTX was blocked by the fragment The hydrophobic portion of MTX is expected to be promising molecular probes for identifying the target proteins of MTX..
106. Respati Swasono, Ryota Mouri, Nagy Morsy, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Sterol Effect on Interaction between Amphidinol 3 and Liposomal Membrane as Evidenced by Surface Plasmon Resonance., Bioorg. Med. Chem. Lett., 10.1016/j.bmcl.2010.02.025, 20, 2215-2218, 2010.01.
107. Satoru Ujihara, Tohru Oishi, Ryota Mouri, Rie Tamate, Keiichi Konoki, Nobuaki Matsumori, Michio Murata, Yasukatsu Oshima, Naoyuki Sugiyama, Masaru Tomita, Yasushi Ishihama, Detection of Rap1A as a yessotoxin binding protein from blood cell membranes., Bioorg. Med. Chem. Lett., 10.1016/j.bmcl.2010.09.080, 20, 6443-6446, 2010.01.
108. Tohru Oishi, Kouichiro Ootou, Hajime Shibata, Michio Murata, Second-Generation Synthesis of Endogenous Sperm-Activating and Attracting Factor (SAAF) Isolated from the Ascidian Ciona intestinalis., Tetrahedron Lett., 10.1016/j.tetlet.2010.03.011, 51, 2600-2602, 2010.01.
109. Tohru Oishi, Tomoyoshi Imaizumi, Michio Murata, Reductive Etherification under Microfluidic Conditions: Application to Practical Synthesis of the FGHIJ-Ring System of Yessotoxin., Chem. Lett., 10.1246/cl.2010.108, 39, 2, 108-109, 2010.01.
110. Respati Swasono, Ryota Mouri, Nagy Morsy, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Sterol Effect on Interaction between Amphidinol 3 and Liposomal Membrane as Evidenced by Surface Plasmon Resonance., Bioorg. Med. Chem. Lett., 1016/j.bmcl.2010.02.025, 20, 7, 2215-2218, 2010.04, The affinity of amphidinol 3 (AM3) to phospholipid membranes in the presence and absence of sterol was examd. by surface plasmon resonance (SPR) expts. The results showed that AM3 has 1000 and 5300 times higher affinity for cholesterol- and ergosterol-​contg. liposomes, resp., than those without sterol. The two-​state reaction model well reproduced the sensor grams, which indicated that the interaction is composed of two steps, which correspond to binding to the membrane and internalization to form stable complexes. .
111. Respati T. Swasono, Mitsunori Kanemoto, Nobuaki Matsumori, Tohru Oishi, Michio Murata , Structural reevaluations of amphidinol 3, a potent antifungal compound from dinoflagellate
, Heterocycles , 10.3987/COM-10-S(E)86, 82, 2, 1359-1369, 2011.01, Among other homologues, amphidinol 3 (AM3) is the most potent antifungal compd. isolated from the dinoflagellate Amphidinium klebsii. AM3 undergoes conformational changes in org. solvents while it takes relatively fixed configuration in a membrane model. By using NMR data of peracetyl AM3, we were able to confirm the configuration of C50-C51 of AM3 which remained uncertain in our previous study. .
112. Yusuke Kasai, Nobuaki Matsumori, Hiroyuki Ueno, Kenichi Nonomura, Shinya Yano, Murata Michio, Tohru Oishi , Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 3, Organic & Biomolecular Chemistry , 10.1039/c0ob00685h, 9, 5, 1437-1442, 2011.01, Two well-known antifungals, amphotericin B (AmB) and amphidinol 3 (AM3), are thought to exert antifungal activity by forming ion-permeable channels or pores together with sterol mols. However, detailed mol. recognitions for AmB-sterol and AM3-sterol in lipid bilayers have yet to be detd. Toward 19F NMR-based investigation of the mol. recognition underlying their potent antifungal activity, we synthesized 6-fluoro-ergosterol I in five steps via ring opening of (5α,6α)-epoxide of ergosterol acetate using a novel combination of TiF4 and n-Bu4N+Ph3SiF2-. Then we evaluated its activity of promoting pore formation of AmB and AM3, and found that pore formation of AmB was barely promoted by 6-F-ergosterol in clear contrast to the dramatic promotion effect of unmodified ergosterol, whereas AM3 activity was markedly enhanced in the presence of 6-F-ergosterol, which was comparable to that of unmodified ergosterol. These results indicate that the introduction of an F atom at C6 position of ergosterol plays an inhibitory role in interacting with AmB, but it is not the case with AM3..
113. Keisuke Maruyoshi, Toshiyuki Yamaguchi, Tetsuo Demura, Nobuaki Matsumori, Tohru Oishi, Michio Murata , Conformations of spermine in adenosine triphosphate complex: The structural basis for weak bimolecular interactions of major cellular electrolytes
, Chemistry--A European Journal , 10.1002/chem.201002759, 17, 17, 4788-4795, 2011.03, Selectively 2H- and 13C-labeled spermines (SPM) were efficiently synthesized and analyzed by NMR spectroscopy to det. the spin-spin coupling consts. for 6 conformationally relevant bonds. SPM that is composed of 3 alkyl moieties, a butanylene, and 2 propanylene chains underwent a conformational change when interacting with multivalent anions (e.g., ATP, ATP-Mg2+, and tripolyphosphate). Upon interaction with ATP, the C-C bonds, which affect the distance between the neighboring pairs of NH4+ groups (i.e., N1/N5 and N5/N5'), increased the population of gauche rotamers by 17-20% relative to those in the 4 HCl salt of SPM. However, the trend in increments of the gauche conformers for the SPM-ATP complex profoundly differed from that of the spermidine (SPD)-ATP complex. This implied that SPM may preferentially recognize the adenylyl group of ATP rather than the tripolyphosphate moiety. This may account for the higher affinity of SPM to ATP-Mg2+ than with that of SPD, which chiefly interacts with β- and γ-phosphates and is easily replaced by Mg2+. These results may provide a clue for the further understanding of the structural basis of polyamine biol. functions. .
114. Nobuaki Matsumori, Norio Tanada, Kohei Nozu, Hiroki Okazaki, Tohru Oishi, Michio Murata , Design and Synthesis of Sphingomyelin-Cholesterol Conjugates and Their Formation of Ordered Membranes, Chemistry--A European Journal , 10.1002/chem.201100849, 17, 31, 8568-8575, 2011.07, A lipid raft is a cholesterol (Chol)-rich microdomain floating in a sea of lipid bilayers. Although Chol is thought to interact preferentially with sphingolipids such as sphingomyelin (SM), rather than with glycerophospholipids, the origin of the specific interaction has remained unresolved, primarily because of the high mobility of lipid mols. and weak intermol. interactions. In this study, we synthesized SM-Chol conjugates with functionally designed linker portions to restrain Chol mobility and examd. their formation of ordered membranes by a detergent insoly. assay, fluorescence anisotropy expts., and fluorescence-quenching assay. In all of the tests, membranes prepd. from the conjugates showed properties of ordered domains comparable to a SM-Chol (1:1) membrane. To gain insight into the structure of bilayers composed from the conjugates, we performed mol. dynamics simulations with 64 mols. of the conjugates, which suggested that the conjugates form a stable bilayer structure by bending at the linker portion and, mostly, reproduce the hydrogen bonds between the SM and Chol portions. These results imply that the mol. recognition between SM and Chol in an ordered domain is essentially reproduced by the conjugated mols. and, thus, demonstrates that these conjugate mols. could potentially serve as mol. probes for understanding mol. recognition in lipid rafts.

.
115. Yuichi Umegawa, Yasuo Nakagawa, Kazuaki Tahara, Hiroshi Tsuchika, Nobuaki Matsumori, Tohru Oishi, Michio Murata, Head−to−Tail Interaction between Amphotericin B and Ergosterol Occurs in Hydrated Phospholipid Membrane. , Biochemistry , 10.1021/bi2012542, 51, 1, 83−89, 2011.11, Amphotericin B (AmB) is thought to exert its antifungal activity by forming an ion-​channel assembly in the presence of ergosterol. In the present study we aimed to elucidate the mode of mol. interactions between AmB and ergosterol in hydrated phospholipid bilayers using the rotational echo double resonance (REDOR) spectra. We first performed 13C{19F}​REDOR expts. with C14-​19F-​labeled AmB and biosynthetically 13C-​labeled ergosterol and implied that both "head-​to-​head" and "head-​to-​tail" orientations occur for AmB-​ergosterol interaction in the bilayers. To further confirm the "head-​to-​tail" pairing, 13C-​labeled ergosterol at the di-​Me terminus (C26​/C27) was synthesized and subjected to the REDOR measurements. The spectra unambiguously demonstrated the presence of a "head-​to-​tail" orientation for AmB-​ergosterol pairing. In order to obtain information on the position of the di-​Me terminus of ergosterol in membrane, 13C{31P}​REDOR were carried out using the labeled ergosterol and the phosphorus atom of a POPC headgroup. Significant REDOR dephasing was obsd. at the C26​/C27 signal of ergosterol in the presence of AmB, but not in the absence of AmB, clearly indicating that the side-​chain terminus of ergosterol in the AmB complex comes close to the bilayer surface. .
116. Toshiyuki Yamaguchi, Takashi Suzuki, Tomokazu Yasuda, Tohru Oishi, Nobuaki Matsumori, Michio Murata, NMR−based conformational analysis of sphingomyelin in bicelles. , Bioorg. Med. Chem. , 10.1016/j.bmc.2011.11.001, 20, 1, 270−278, 2012.01, Sphingomyelin (SM) is a common sphingolipid in mammalian membranes and is known to be substantially involved in cellular events such as the formation of lipid rafts. Despite its biol. significance, conformation of SM in a membrane environment remains unclear because the noncryst. property and anisotropic environment of lipid bilayers hampers the application of x-​ray crystallog. and NMR measurements. In this study, to elucidate the conformation of SM in membranes, the authors utilized bicelles as a substitute for a lipid bilayer membrane. First, the authors demonstrated through 31P NMR, 2H NMR, and dynamic light scattering expts. that SM forms both oriented and isotropic bicelles by changing the ratio of SM​/dihexanoyl phosphatidylcholine. Then, the authors detd. the conformation of SM in isotropic bicelles on the basis of coupling consts. and NOE correlations in 1H NMR and found that the C2-​C6 and amide groups of SM take a relatively rigid conformation in bicelles. .
117. Tohru Oishi, Keiichi Konoki, Masahiro Kunitake, Rie Tamate, Kohei TORIKAI, Futoshi Hasegawa, Nobuaki Matsumori, Michio Murata, Artificial ladder−shaped polyethers that inhibit maitotoxin−induced Ca2+ influx in rat glioma C6 cells. , Bioorg. Med. Chem. Lett., 10.1016/j.bmcl.2012.04.053, 22, 11, 3619−3622, 2012.06, Maitotoxin (MTX) is a ladder-​shaped polyether produced by the epiphytic dinoflagellate Gambierdiscus toxicus. It is known to elicit potent toxicity against mammals and induce influx of Ca2+ into cells. An artificial ladder-​shaped polyether possessing a 6​/7​/6​/6​/7​/6​/6 heptacyclic ring system, which was designed for elucidating interactions with transmembrane proteins, was found to be the most potent inhibitor against MTX-​induced Ca2+ influx that has ever been reported. .
118. Nobuaki Matsumori, Tomokazu Yasuda, Hiroki Okazaki, Takashi Suzuki, Toshiyuki Yamaguchi, Tetsuro Takano, Hiroshi Tsuchika, Mototsugu Doi, Tohru Oishi, Michio Murata, Comprehensive Molecular Motion Capture for Sphingomyelin by Site−Specific Deuterium Labeling. , Biochemistry, 10.1021/bi3009399, 51, 42, 8363–8370, 2012.09, Lipid rafts have attracted much attention because of their significant functional roles in membrane-​assocd. processes. It is thought that sphingomyelin and cholesterol are essential for forming lipid rafts; however, their motion characteristics are not fully understood despite numerous studies. Here the authors show accurate local motions encompassing an entire sphingomyelin mol., which were captured by measuring quadrupole splittings for 19 kinds of site-​specifically deuterated sphingomyelins (i.e., mol. motion capture of sphingomyelin)​. The quadrupole splitting profiles, which are distinct from those reported from perdeuterated sphingomyelins or simulation studies, reveal that cholesterol enhances the order in the middle parts of the alkyl chains more efficaciously than at the shallow positions. Comparison with dimyristoylphosphocholine bilayers suggests that cholesterol is deeper in sphingomyelin bilayers, which likely explains the so-​called umbrella effect. Also (i) the C2'-​C3' bond predominantly takes the gauche conformation, (ii) the net ordering effect of cholesterol in sphingomyelin bilayers is not larger than that in phosphatidylcholine bilayers, (iii) cholesterol has no specific preference for the acyl or sphingosine chain, (iv) the acyl and sphingosine chains seem mismatched by about two methylene lengths, and (v) the motion of the upper regions of sphingomyelin chains is less temp. dependent than that of lower regions probably due to intermol. hydrogen bond formation among SM mols. These insights into the at.-​level dynamics of sphingomyelin provide crit. clues to understanding the mechanism of raft formation. .
119. Yoshiyuki Manabe, Makoto EBINE, Nobuaki Matsumori, Michio Murata, Tohru Oishi, Confirmation of the Absolute Configuration at C45 of Amphidinol 3. , J. Nat. Prod. , 10.1021/np300604w, 75, 11, 303–312, 2012.11, Amphidinol 3 (AM3), a membrane-active agent isolated from the dinoflagellate Amphidinium klebsii, consists of a long carbon chain containing twenty five stereogenic centers. Although the absolute configuration of AM3 was determined by extensive NMR analysis and degradation of the natural product, the partial structure corresponding to the tetrahydropyran ring system was found to be antipodal to that of karlotoxin 2, a structurally related compound recently isolated from the dinoflagellate Karlodinium veneficum. By extensive degradation of the natural product and conversion of the resulting alcohol to an MTPA ester, the absolute configuration at C45 of AM3 was confirmed to be R, supporting the originally proposed structure..
120. Tohru Oishi, Convergent method via α-cyano ethers
A powerful strategy for synthesizing ladder-shaped polyethers, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.70.1170, 70, 11, 1170-1177, 2012.12, Ladder-shaped polyether (LSP) toxins attract considerable attention among synthetic organic chemists due to their potent biological activities coupled with their unique molecular structures. Although a number of methods for synthesizing LSPs have been reported, developments of convergent and practical methods are necessary for efficient synthesis of LSPs in order to reveal their biological function at the molecular level and because of their limited availability from natural sources. During the course of our synthetic studies of LSPs, we developed a convergent method via α-cyano ethers (α-cyano ether method). An additional two rings can be constructed through the coupling of fragments, which is an advantage of this strategy for the construction of polycyclic systems. Medium-sized cyclic ethers are formed by ring-closing metathesis, and tetrahydropyran rings are stereoselectively constructed by reductive etherification or thioacetal formation followed by alkylation. The α-cyano ether method was successfully applied to the synthesis of the partial structure corresponding to the ABCDEFGHIJ ring system of yessotoxin, where utilization of a microflow reactor was found to be effective for reductive etherification. The α-cyano ether method was also applicable for synthesizing the WXYZA-B-C-ring system of maitotoxin, and designed artificial tetra-, hepta-, and decacyclic LSPs..
121. Matsumori, Nobuaki; Hiradate, Yuki; Shibata, Hajime; Oishi, Tohru; Shimma, Shuichi; Toyoda, Michisato; Hayashi, Fumiaki; Yoshida, Manabu; Murata, Michio; Morisawa, Masaaki , A Novel Sperm-​Activating and Attracting Factor from the Ascidian Ascidia sydneiensis, Organic Letters , 10.1021/ol303172n, 15, 2, 294-297, 2013.01, A novel SAAF was isolated from the title ascidian. The structure was elucidated using the entire sample of 4 nmol, suggesting that the position of the OH group confers genus-​specificity to sperm chemotaxis in ascidians. This study not only provides insight into the chem. tactics in sperm chemotaxis but demonstrates that the innovative techniques allow structure detn. of natural products in trace amts. .
122. Ebine, Makoto; Kanemoto, Mitsunori; Manabe, Yoshiyuki; Konno, Yosuke; Sakai, Ken; Matsumori, Nobuaki; Murata, Michio; Oishi, Tohru , Synthesis and Structure Revision of the C43-​C67 Part of Amphidinol 3, Organic Letters , 10.1021/ol401176a, 15, 11, 2846-2849, 2013.05, Stereoselective synthesis of the C43-​C67 part of amphidinol 3 (AM3) and its C51-​epimer, I (R1 = OH, R2 = H; R1 = H, R2 = OH)​, was achieved starting from a common intermediate corresponding to the tetrahydropyran moiety of AM3, via asym. oxidns. and Julia-​Kocienski olefination. By comparing NMR data of the synthetic specimens with those of AM3, the abs. configuration at C51 of AM3 was revised from R to S. .
123. Kazuki Kajitani, Tomomi KOSHIYAMA, Akihiro Hori, Ryo Ohtani, Akio Mishima, Kohei TORIKAI, Makoto EBINE, Tohru Oishi, Susumu Kitagawa, Masaaki OHBA, Guest responsivity of a two−dimensional coordination polymer incorporating a cholesterol−based co−ligand. , Dalton Trans. 2013,, 10.1039/C3DT51465J, 42, 31, 15893−15897, 2013.07, To implement specific guest responsivity, a hydrophobic cholesterol-based co-ligand, cholest-5-en-3-yl-4-isonicotinate (Cholpy), was incorporated into a two-dimensional Hofmann-type Co(II)Ni(II) coordination polymer. The chemically programmed structure successfully demonstrated the unique guest response with remarkable chromatic changes..
124. Kazuki Kajitani, Tomomi Koshiyama, Akihiro Hori, Ryo Otani, Akio Mishima, Kohei Torikai, Makoto Ebine, Tohru Oishi, Masaki Takata, Susumu Kitagawa, Masaaki Ohba, Guest responsivity of a two-dimensional coordination polymer incorporating a cholesterol-based co-ligand, Dalton Transactions, 10.1039/c3dt51465j, 42, 45, 15893-15897, 2013.12, To implement specific guest responsivity, a hydrophobic cholesterol-based co-ligand, cholest-5-en-3-yl-4-isonicotinate (Cholpy), was incorporated into a two-dimensional Hofmann-type Co(ii)Ni(ii) coordination polymer. The chemically programmed structure successfully demonstrated the unique guest response with remarkable chromatic changes..
125. Masahiro Kunitake, Takahiro Oshima, Keiichi Konoki, Michio Murata, Tohru Oishi, Synthesis and Biological Activity of the C’D’E’F’ Ring System of Maitotoxin. , J. Org. Chem. , 10.1021/jo5005235, 79, 11, 4948-4962, 2014.03, Stereoselective synthesis of the C’D’E’F’ ring system of maitotoxin was achieved starting from the E’ ring through successive formation of the D’ and C’ rings based on SmI2-mediated reductive cyclization. Construction of the F’ ring was accomplished via Suzuki-Miyaura cross coupling with a side chain fragment and Pd(II)-catalyzed cyclization of an allylic alcohol. The C’D’E’F’ ring system inhibited MTX-induced Ca2+ influx in rat glioma C6 cells with an IC50 value of 59 microM.
126. Hisaaki Onoue, Tomomi Baba, Keiichi Konoki, Kohei TORIKAI, Makoto EBINE, Tohru Oishi, Synthesis and Biological Activity of the QRS Ring System of Maitotoxin. , Chem. Lett., 10.1246/cl.140789, 43, 12, 1904-1906, 2014.09, Maitotoxin (MTX) is a ladder-shaped polyether produced by an epiphytic dinoflagellate. As a part of our structure-activity relationship studies using synthetic partial structures of MTX, the QRS ring comprised of a 6/6/7 tricyclic system was synthesized through stereoselective construction of the five contiguous stereogenic centers on the Q ring via i) coupling of a Weinreb amide and a furyllithium, followed by ii) Noyori asymmetric transfer hydrogenation, iii) Achmatowicz reaction, iv) chemoselective methylation of a methyl acetal in the presence of a carbonyl group by treatment with Me2Zn/BF3·OEt2, v) highly diastereoselective dihydroxylation, and vi) ring expansion of a six-membered to a seven-membered ring ketone. The synthetic specimen inhibited MTX-induced Ca2+ influx with an IC50 value of 44 microM..
127. Yasuo Nakagawa, Yuichi Umegawa, Kenichi Nonomura, Naohiro Matsushita, Tetsuro Takano, Hiroshi Tsuchika, Shinya Hanashima, Tohru Oishi, Nobuaki Matsumori, Michio Murata, Axial Hydrogen at C7 Position and Bumpy Tetracyclic Core Markedly Reduce Sterol's Affinity to Amphotericin B in Membrane., Biochemistry, 10.1021/bi3009399, 51, 42, 8363–8370, 2014.12, Lipid rafts have attracted much attention because of their significant functional roles in membrane-​assocd. processes. It is thought that sphingomyelin and cholesterol are essential for forming lipid rafts; however, their motion characteristics are not fully understood despite numerous studies. Here the authors show accurate local motions encompassing an entire sphingomyelin mol., which were captured by measuring quadrupole splittings for 19 kinds of site-​specifically deuterated sphingomyelins (i.e., mol. motion capture of sphingomyelin)​. The quadrupole splitting profiles, which are distinct from those reported from perdeuterated sphingomyelins or simulation studies, reveal that cholesterol enhances the order in the middle parts of the alkyl chains more efficaciously than at the shallow positions. Comparison with dimyristoylphosphocholine bilayers suggests that cholesterol is deeper in sphingomyelin bilayers, which likely explains the so-​called umbrella effect. Also (i) the C2'-​C3' bond predominantly takes the gauche conformation, (ii) the net ordering effect of cholesterol in sphingomyelin bilayers is not larger than that in phosphatidylcholine bilayers, (iii) cholesterol has no specific preference for the acyl or sphingosine chain, (iv) the acyl and sphingosine chains seem mismatched by about two methylene lengths, and (v) the motion of the upper regions of sphingomyelin chains is less temp. dependent than that of lower regions probably due to intermol. hydrogen bond formation among SM mols. These insights into the at.-​level dynamics of sphingomyelin provide crit. clues to understanding the mechanism of raft formation. .
128. Takeshi Tsuruda, Makoto Ebine, Aya Umeda, Tohru Oishi, Stereoselective Synthesis of the C1-C29 Part of Amphidinol 3., J. Org. Chem., 10.1021/jo502322m, 80, 2, 859–871, 2015.01, Stereoselective synthesis of the C1-C29 part of amphidinol 3 (AM3) was achieved. The C1-C20 part was assembled from three building blocks via regioselective cross metathesis to form the C4-C5 double bond, and addition of an alkenyllithium and a lithium acetylide to two Weinreb amides followed by asymmetric reduction to form the C9-C10 and C14-C15 bonds, respectively. The C21-C29 part was synthesized via successive cross metathesis and oxa-Michael addition sequence to construct the 1,3-diol system at C25 and C27, and Brown asymmetric crotylation to introduce the stereogenic centers at C23 and C24. Coupling of the C1-C20 and C21-C29 parts was achieved by Julia-Kocienski olefination, and regio- and stereoselective dihydroxylation of the C20-C21 double bond in the presence of the C4-C5 and C8-C9 double bonds to afford the C1-C29 part of AM3..
129. Yasuo Nakagawa, Yuichi Umegawa, Kenichi Nonomura, Naohiro Matsushita, Tetsuro Takano, Hiroshi Tsuchika, Shinya Hanashima, Tohru Oishi, Nobuaki Matsumori, Michio Murata, Axial Hydrogen at C7 Position and Bumpy Tetracyclic Core Markedly Reduce Sterol's Affinity to Amphotericin B in Membrane, Biochemistry, 10.1021/bi5012942, 54, 2, 303–312, 2015.01, The interaction of amphotericin B (AmB) with fungal ergosterol (Erg) is stronger than its interaction with mammalian cholesterol (Cho), and this property of AmB as an antifungal drug is thought to be responsible for its selective toxicity toward fungi. However, the mechanism by which AmB recognizes the structural differences between sterols, particularly minor difference in the sterol alicyclic portion, is largely unknown. Thus, to investigate the mode of interaction between AmB and the sterol core, we assessed the affinity of AmB to various sterols with different alicyclic structures. Ion flux assays and UV spectral measurements clearly revealed the importance of the Δ7-double bond of the sterol B-ring for interaction with the drug. AmB showed lower affinity for triene sterols, which have double bonds at the Δ5, Δ7, and Δ9 positions. Intermolecular distance measurements by 13C{19F} rotational echo double resonance (REDOR) revealed that the AmB macrolide ring is in closer contact with the steroid core of Erg than it is with the Cho core in the membrane. Conformational analysis suggested that an axial hydrogen atom at C7 of Δ5-sterol (2, 6) and the protruded A-ring of Δ5,7,9-sterol (4, 8) sterically hampered face-to-face contact between the van der Waals surface of the sterol core and the macrolide of AmB. These results further suggest that the α-face of sterol alicycle interacts with the flat macrolide
structure of AmB..
130. Takuya Sato, Tohru Oishi, Torikai, K., 2-​Naphthylmethoxymethyl as a Mildly Introducible and Oxidatively Removable Benzyloxymethyl-​Type Protecting Group, Org. Lett., 10.1021/acs.orglett.5b01408, 17, 12, 3110-3113, 2015.06, The 2-​naphthylmethoxymethyl (NAPOM) group was developed as a protecting group for alcs., phenols, carboxylic acids, and thiols. The NAPOM group can be introduced in extremely mild conditions using 2-​naphthylmethoxymethyl chloride either with diisopropylethylamine as a base or with 2,​6-​lutidine as a base in the presence of tetrabutylammonium iodide at room temp.; under the latter conditions, a monoacetylated diol was protected with minimal concomitant acyl migration. Selective removal of the NAPOM protecting group in the presence of 2-​naphthylmethyl and p-​methoxybenzyl (PMB) groups and, conversely, selective removal of a PMB group in the presence of a NAPOM group were realized. The solvent compatibility of the installation and removal of the NAPOM group was studied; most solvents were compatible with its installation, while deprotections in THF and DMF gave product in reduced yields..
131. Rintaro Koga, Tohru Oishi, Kohei Torikai, Tuned Classical Thermal Aromatization Furnishing an Estrogenic Benzoacridine, Synlett, 10.1055/s-0035-1560521 , 26, 20, 2801-2805, 2015.12, The diversity-​oriented doubling strategy, which generates two 12-​arylbenzoacridines from a single triarylmethanol precursor was developed to construct a library of drug candidates for the identification of biol. active compds. Exploration of this 12-​arylbenzoacridine library furnished a 4'-​OH deriv. as an estrogenic compd..
132. Rintaro Koga, Tohru Oishi, Kohei Torikai, Tuned Classical Thermal Aromatization Furnishing an Estrogenic Benzoacridine, Synlett, 10.1055/s-0035-1560521, 26, 20, 2801-2805, 2015.12, The diversity-oriented doubling strategy, which generates two 12-arylbenzoacridines from a single triarylmethanol precursor was developed to construct a library of drug candidates for the identification of biologically active compounds. Exploration of this 12-arylbenzoacridine library furnished a 4′-OH derivative as an estrogenic compound..
133. Yasuo Nakagawa, Yuichi Umegawa, Naohiro Matsushita, Tomoya Yamamoto, Hiroshi Tsuchikawa, Shinya Hanashima, Tohru Oishi, Nobuaki Matsumori, Michio Murata, The Structure of the Bimolecular Complex between Amphotericin B and Ergosterol in Membranes Is Stabilized by Face-to-Face van der Waals Interaction with Their Rigid Cyclic Cores, Biochemistry, 10.1021/acs.biochem.6b00193, 55, 24, 3392-3402, 2016.06, Amphotericin B (AmB) is a polyene macrolide antibiotic isolated from Streptomyces nodosus. The antifungal activity of AmB can be attributed to the formation of an ion-channel assembly in the presence of ergosterol (Erg), in which there are two different AmB-Erg orientations, parallel and antiparallel, as reported previously. In this study, to elucidate the structures of those AmB-Erg complexes based on solid-state nuclear magnetic resonance, a 19F-labeled AmB derivative was newly prepared by a hybrid synthesis that utilized degradation products from the drug. Using the 2-(trimethylsilyl)ethoxymethyl (SEM) group as the protecting group for the carboxylic acid moiety of AmB, the fully deprotected labeled AmB compounds were obtained successfully. Then, these labeled AmBs were subjected to 13C{19F} rotational-echo double-resonance (REDOR) experiments in hydrated lipid bilayers. The results indicated the coexistence of parallel and antiparallel orientations for AmB and Erg pairing, at a ratio of 7:3. A total of six distances between AmB and Erg were successfully obtained. Geometry analysis using the distance constraints derived from the REDOR experiments provided the plausible AmB-Erg complex structure for both the parallel and antiparallel interactions. The flat macrolide of AmB and the tetracyclic core of Erg closely contacted in a face-to-face manner, thus maximizing the van der Waals interaction between the two molecules. This interaction can be attributed to the coexistence of both the parallel and antiparallel orientations..
134. Takuya Sato, Yohei Joh, Tohru Oishi, Kohei Torikai, 1-Naphthylmethyl and 1-naphthylmethoxymethyl protecting groups
New members of the benzyl- and benzyloxymethyl-type family, Tetrahedron Letters, 10.1016/j.tetlet.2017.04.046, 58, 23, 2178-2181, 2017.01, 1-Naphthylmethyl (NAPI) and 1-naphthylmethoxymethyl (NAPOMI) protecting groups were developed as new members of the benzyl- and benzyloxymethyl-type family. NAPI and NAPOMI can be introduced under conventional conditions, such as NAPIBr/NaH/room temperature (rt), or NAPOMICl/i-Pr2EtN/rt. They can also be removed under conventional conditions, e.g., by dichlorodicyanobenzoquinone (DDQ)- or ceric ammonium nitrate (CAN)-mediated oxidation, or by hydrogenolysis. The specific advantages of these new protecting groups are: i) a less costly synthesis of NAPOMICl compared to NAPOMIICl, ii) the possibility to remove NAPOMII selectively in the presence of NAPOMI by DDQ-mediated oxidation, and iii) the compatibility with strong acids even in the presence of hard nucleophiles..
135. Kohei Torikai, Rintaro Koga, Xiaohui Liu, Kaoru Umehara, Tatsuya Kitano, Kenji Watanabe, Tohru Oishi, Hiroshi Noguchi, Yasuyuki Shimohigashi, Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents, Bioorganic and Medicinal Chemistry, 10.1016/j.bmc.2017.07.067, 25, 20, 5216-5237, 2017.01, Estrogens play undisputedly important physiological roles, but lifetime exposure to estrogens has also been linked to the development of breast cancer. Moreover, imbalanced estrogen levels have been associated with various symptoms such as osteoporosis and menopausal disorders. For the improvement of such estrogen imbalances, estrogenic reagents with regulatory properties have shown promising potential. Herein, we report the construction of a 12-arylbenzoacridine library via a diversity-oriented strategy that furnished non-toxic estrogenic and anti-estrogenic agents. Derivatives with a hydroxy group at the molecular edge exhibit potent binding affinity to the estrogen receptor α (ERα) and ERβ (IC50 < μM), while binding to the estrogen-related receptor γ (ERRγ), i.e., an orphan nuclear receptor on which estrogens often trigger unfavorable events, was not observed. These findings offer valuable insights into 12-arylbenzoacridines as a novel platform for the development of selective estrogen-receptor modulators (SERMs)..
136. Hisaaki Onoue, Riho Marubayashi, Erina Ishikawa, Keiichi Konoki, Kohei Torikai, Makoto Ebine, Michio Murata, Tohru Oishi, Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin, Journal of Organic Chemistry, 10.1021/acs.joc.7b01658, 82, 18, 9595-9618, 2017.01, Structure-activity relationship studies of maitotoxin (MTX), a marine natural product produced by an epiphytic dinoflagellate, were conducted using chemically synthesized model compounds corresponding to the partial structures of MTX. Both enantiomers of the LMNO ring system were synthesized via aldol reaction of the LM ring aldehyde and the NO ring ketone. These fragments were derived from a common cis-fused pyranopyran intermediate prepared through a sequence involving Nozaki-Hiyama-Kishi reaction, intramolecular oxa-Michael addition, and Pummerer rearrangement. The NOPQR(S) ring system, in which the original seven-membered S ring was substituted with a six-membered ring, was also synthesized through the coupling of the QR(S) ring alkyne and the NO ring aldehyde and the construction of the P ring via 1,4-reduction, dehydration, and hydroboration. The inhibitory activities of the synthetic specimens against MTX-induced Ca2+ influx were evaluated. The LMNO ring system and its enantiomer induced 36 and 18% inhibition, respectively, at 300 μM, whereas the NOPQR(S) ring system elicited no inhibitory activity..
137. Makoto Ebine, Yuri Takada, Naoto Yanai, Tohru Oishi, Synthesis of a truncated analog of amphidinol 3 corresponding to the C21C39/C52C67 section, Chemistry Letters, 10.1246/cl.170050, 46, 5, 662-664, 2017.01, As a part of structureactivity relationship studies to elucidate structure requirements for eliciting antifungal activity, an artificial analog of amphidinol 3 (AM3) was designed. A truncated analog corresponding to the C21C39/C52C67 section was synthesized by using SuzukiMiyaura coupling and JuliaKocienski olefination as key steps. An expeditious and versatile method to construct the C53C67 polyene section was also developed based on a linchpin strategy via successive cross-coupling reactions. The analog elicited no antifungal activity, suggesting that the two tetrahydropyran rings of AM3 are necessary to elicit antifungal activity..
138. Hiroshi Tsuchikawa, Yuichi Umegawa, Michio Murata, Tohru Oishi, A synthetic approach to the channel complex structure of antibiotic in a membrane
Backbone
19
F-labeled amphotericin B for solidstate NMR analysis, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.76.1197, 76, 11, 1197-1205, 2018.01, Over 40 years have passed since a well-known hypothesis of a channel-like amphotericin B (AmB) assembly with ergosterol (Erg) was proposed as the mode of action accounting for its selective fungal toxicity. However, no reliable or direct experimental evidence had been obtained until recently mainly because of significant difficulties in structural analysis of the self-assembly of small molecules specifically formed inside a membrane. In this study, we describe the accomplishments in the chemical synthesis of two AmB derivatives with fluorine labeling in the molecular skeleton for applying solid-state NMR techniques. The interatomic distance measurements using these chemically prepared probes have successfully shown the detailed AmB-Erg bimolecular interaction in the channel structure for the first time. The latest solid-state NMR analysis backed by synthetic chemistry is expected to achieve a breakthrough in elucidating the long-unsolved AmB channel architecture..
139. Naoya Osato, Hisaaki Onoue, Yoshiki Toma, Kohei Torikai, Makoto Ebine, Masayuki Satake, Tohru Oishi, Convergent syntheses of the WXYZ ring of maitotoxin and the HIJK ring of brevisulcenal-F, Chemistry Letters, 10.1246/cl.171056, 47, 3, 265-268, 2018.01, A convergent method to construct the 6/7/6/6-tetracyclic ether system possessing contiguous angular methyl groups was developed. The key steps of the synthesis involve coupling of a lithium acetylide and an aldehyde, cyclodehydration of a hydroxy ketone to form a dihydropyran, ring expansion of a six-membered ring ketone into a seven-membered one, and methylation of a mixed-thioacetal. Based on this strategy, syntheses of the WXYZ ring of maitotoxin and the HIJK ring of brevisulcenal-F were achieved, and the stereochemistry of the HIJK ring of brevisulcenal-F was confirmed..
140. Sota Katayama, Tomoyuki Koge, Satoko Katsuragi, Shuji Akai, Tohru Oishi, Flow synthesis of (3R)- and (3S)-(E)-1-iodohexa-1,5-dien-3-ol
Chiral building blocks for natural product synthesis, Chemistry Letters, 10.1246/cl.180475, 47, 9, 1116-1118, 2018.01, A concise procedure to prepare optically active (3R)- and (3S)-(E)-1-iodohexa-1,5-dien-3-ol was developed. Ethyl (E)-3-iodoacrylate was converted to racemic (E)-1-iodohexa-1,5-dien-3-ol under flow and batch conditions via successive half reduction followed by Grignard reaction. Kinetic resolution of the racemic alcohol was achieved under flow conditions by using lipase packed in a column to afford (3S)-(E)-1-iodohexa-1,5-dien-3-ol and corresponding (3R)-acetate. Removal of the acetyl group was also carried out under flow conditions by using ion exchange resin packed in a column and (3R)-(E)-1-iodohexa-1,5-dien-3-ol was obtained after simple evaporation of the eluent..
141. Hiroki Yamamoto, Kohei Torikai, Makoto Ebine, Tohru Oishi, Synthesis of 6/6/6-tricyclic ether system via Achmatowicz and intramolecular oxa-michael reactions, Heterocycles, 10.3987/COM-17-S(T)10, 97, 1, 158-162, 2018.01, Synthesis of 6/6/6-tricyclic ethers possessing 1,3-diaxial methyl groups was examined via Achmatowicz reaction and intramolecular oxa-Michael reaction. A key precursor was prepared via coupling of an aldehyde with a furyllithium derivative followed by radical deoxygenation of the resulting secondary alcohol. The intramolecular oxa-Michael reaction proceeded in a stereoselective manner to afford cis-fused product as a single isomer..
142. Tomoyuki Koge, Yuma Wakamiya, Makoto Ebine, Tohru Oishi, Synthesis of an analog of amphidinol 3 corresponding to the c31-c67 section, Heterocycles, 10.3987/COM-18-13927, 96, 7, 1197-1202, 2018.01, An artificial analog corresponding to the C31-C67 section of amphidinol 3 (AM3) was designed as a part of the structure-activity relationship studies to elucidate structure requirements for eliciting antifungal activity. To reduce the number of synthetic steps, the 43-deoxy-51-epi derivative containing common tetrahydropyran ring system was designed and synthesized from a pivotal intermediate in 17 steps. The analog elicited no antifungal activity, suggesting that not only the two tetrahydropyran rings, but also polyol section of AM3 are necessary to elicit antifungal activity..
143. Tomohiro Watanabe, Hajime Shibata, Makoto Ebine, Hiroshi Tsuchikawa, Nobuaki Matsumori, Michio Murata, Manabu Yoshida, Masaaki Morisawa, Shu Lin, Kosei Yamauchi, Ken Sakai, Tohru Oishi, Synthesis and complete structure determination of a sperm-activating and -attracting factor isolated from the ascidian ascidia sydneiensis, Journal of Natural Products, 10.1021/acs.jnatprod.7b01052, 81, 4, 985-997, 2018.04, For the complete structure elucidation of an endogenous sperm-activating and -attracting factor isolated from eggs of the ascidian Ascidia sydneiensis (Assydn-SAAF), its two possible diastereomers with respect to C-25 were synthesized. Starting from ergosterol, the characteristic steroid backbone was constructed by using an intramolecular pinacol coupling reaction and stereoselective reduction of a hydroxy ketone as key steps, and the side chain was introduced by Julia-Kocienski olefination. Comparison of the NMR data of the two diastereomers with those of the natural product led to the elucidation of the absolute configuration as 25S; thus the complete structure was determined and the first synthesis of Assydn-SAAF was achieved..
144. Yuma Wakamiya, Makoto Ebine, Mariko Murayama, Hiroyuki Omizu, Nobuaki Matsumori, Michio Murata, Tohru Oishi, Synthesis and Stereochemical Revision of the C31–C67 Fragment of Amphidinol 3, Angewandte Chemie - International Edition, 10.1002/anie.201712167, 57, 21, 6060-6064, 2018.05, Amphidinol 3 (AM3) is a marine natural product produced by the dinoflagellate Amphidinium klebsii. Although the absolute configuration of AM3 was determined in 1999 by extensive NMR analysis and degradation of the natural product, it was a daunting task because of the presence of numerous stereogenic centers on the acyclic carbon chain and the limited availability from natural sources. Thereafter, revisions of the absolute configurations at C2 and C51 were reported in 2008 and 2013, respectively. Reported herein is the revised absolute configuration of AM3: 32S, 33R, 34S, 35S, 36S, and 38S based on the chemical synthesis of partial structures corresponding to the C31–C67 fragment of AM3 in combination with degradation of the natural product. The revised structure is unique in that both antipodal tetrahydropyran counterparts exist on a single carbon chain. The structural revision of AM3 may affect proposed structures of congeners related to the amphidinols..
145. Milandip Karak, Tohru Oishi, Kohei Torikai, Synthesis of anti-tubercular marine alkaloids denigrins A and B, Tetrahedron Letters, 10.1016/j.tetlet.2018.06.013, 59, 29, 2800-2803, 2018.07, The first synthesis of anti-tubercular marine alkaloids denigrins A and B were accomplished in three and five steps and 62% and 31% overall yields respectively, from maleic anhydride. The key features of the synthesis include efficient Mizoroki-Heck reaction, geometry-controlled vinylogous aldol condensation, and one-pot lactamization. The synthesis first demonstrates the serviceability of maleic anhydride in palladium-catalyzed cross-coupling reactions with diaryliodonium salt..
146. Milandip Karak, Yohei Joh, Masahiko Suenaga, Tohru Oishi, Kohei Torikai, 1,2- trans Glycosylation via Neighboring Group Participation of 2- O-Alkoxymethyl Groups
Application to One-Pot Oligosaccharide Synthesis, Organic Letters, 10.1021/acs.orglett.9b00220, 2019.01, The use of 2-O-alkoxymethyl groups as effective stereodirecting substituents for the construction of 1,2-trans glycosidic linkages is reported. The observed stereoselectivity arises from the intramolecular formation of a five-membered cyclic architecture between the 2-O-alkoxymethyl substituent and the oxocarbenium ion, which provides the expected facial selectivity. Furthermore, the observed stereocontrol and the extremely high reactivity of 2-O-alkoxymethyl-protected donors allowed development of a one-pot sequential glycosylation strategy that should become a powerful tool for the assembly of oligosaccharides..
147. Tohru Oishi, Design and synthesis of artificial ladder-shaped polyethers for exploring biological functions, Heterocycles, 10.3987/REV-18-SR(F)1, 99, 1, 21-53, 2019.01, Ladder-shaped polyethers (LSPs) are marine natural products produced by dinoflagellates. The unique molecular structure and interesting biological activities have attracted considerable attention of the synthetic community. On the other hand, artificial ladder-shaped polyethers (ALPs) have been designed and synthesized for exploring biological functions. In this review, design and synthesis of ALPs are summarized focusing on the development of synthetic strategies and methodologies..
148. Takaya Yasudomi, Hiroyuki Yakushiji, Kohei Torikai, Makoto Ebine, Tohru Oishi, Unified synthesis of the DEF and GhI ring systems of maitotoxin, Chemistry Letters, 10.1246/cl.190479, 48, 9, 1156-1159, 2019.01, Unified synthesis of 6/6/6-tricyclic ethers corresponding to the DEF and GHI ring systems of maitotoxin was achieved from a common intermediate prepared from a furan derivative and a terminal olefin via FujiwaraMoritani reaction, followed by Sharpless asymmetric dihydroxylation, and Achmatowicz reaction. The DEF ring was synthesized from the common intermediate via regio- and stereoselective borylation of an enone, and methylation of an S, O-acetal. On the other hand, the GHI ring was synthesized from the common intermediate via reductive etherification, Sharpless asymmetric dihydroxylation, and BartonMcCombie deoxygenation..