Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
KATSUHIKO TOMOOKA Last modified date:2022.06.15

Professor / Design of Functional Organic Molecules, Department of Molecular and Material Science / Department of Applied Molecular Chemistry / Institute for Materials Chemistry and Engineering

1. Eigo Ikushima, Shin Ishikane, Takehiro Kishigami, Hiroaki Matsunaga, Kazunobu Igawa, Katsuhiko Tomooka, Yosuke Nishimura, Fumi Takahashi-Yanaga, 2,5-Dimethylcelecoxib attenuates cardiac fibrosis caused by cryoinjury-induced myocardial infarction by suppressing the fibroblast-to-myofibroblast transformation via inhibition of the TGF-β signaling pathway, Biochemical Pharmacology, 10.1016/j.bcp.2022.114950, 197, 2022.03.
2. Jumpei Taguchi, Kota Kimura, Kazunobu Igawa, Katsuhiko Tomooka, Takamitsu Hosoya, 3-Azidoarynes: Generation and Regioselective Reactions, Chemistry Letters, 10.1246/cl.210632, 51, 2, 94-98, 2022.02.
3. Yuuya Kawasaki, Ryota Kamikubo, Yuta Kumegawa, Kouhei Ogawa, Takeru Kashiwagi, Yusuke Ano, Kazunobu Igawa, Katsuhiko Tomooka, Preparation of enantioenriched helical- and axial-chiral molecules by dynamic asymmetric induction, Chemical Communications, 10.1039/d1cc05881a, 58, 10, 1605-1608, 2022.02.
4. Yui Fujii, Makoto Yoritate, Kana Makino, Kazunobu Igawa, Daiki Takeda, Daiki Doiuchi, Katsuhiko Tomooka, Tatsuya Uchida, Go Hirai, Preparation of oxysterols by C–H oxidation of dibromocholestane with ru(Bpga) catalyst, Molecules, 10.3390/molecules27010225, 27, 1, 2022.01.
5. Fumi Seto-Tetsuo, Masaki Arioka, Koichi Miura, Takeru Inoue, Kazunobu Igawa, Katsuhiko Tomooka, Fumi Takahashi-Yanaga, Toshiyuki Sasaguri, DIF-1 inhibits growth and metastasis of triple-negative breast cancer through AMPK-mediated inhibition of the mTORC1-S6K signaling pathway, Oncogene, 10.1038/s41388-021-01958-4, 40, 37, 5579-5589, 2021.09.
6. Igawa, K.; Asano, S.; Yoshida, Y.; Kawasaki, Y.; Tomooka, K., Analysis of Stereochemical Stability of Dynamic Chiral Molecules using an Automated Microflow Measurement System, J. Org. Chem., in press, 2021.07.
7. Makio, N.; Sakata, Y.; Kuribara, T.; Adachi, K.; Hatakeyama, Y.; Meguro, T.; Igawa, K.; Tomooka, K.; Hosoya, T.; Yoshida, S. , (Hexafluoroacetylacetonato)copper(I)-cycloalkyne complexes as protected cycloalkynes, Chem. Commun, 10.1039/D0CC05182A, 56, in press, 2020.08.
8. Adachi, K.; Meguro, T.; Sakata, Y.; Igawa, K.; Tomooka, K.; Hosoya, T.;Yoshida, S., Selective strain-promoted azide-alkyne cycloadditions through transient protection of bicyclo[6.1.0]nonynes with silver or gold
, Chem. Commun, 10.1039/D0CC04606J, 56, 9823-9826, 2020.08.
9. Murakami, A.; Hayashi, J.; Igawa, K.; Tsutsumi, M.; Tomooka, K.; Nagai, H.; Nehira, T., Natural Dolapyrrolidone: Isolation and Absolute Stereochemistry of a Substructure of Bioactive Peptides, Chirality, 10.1002/chir.23264 , 32, 1152-1159, 2020.08.
10. Sugahara, T.; Ferao, A.E.; Rey, A.; Guo, J.; Aoyama, S.; Igawa, K.; Tomooka, K.; Sasamori, T.; Hashizume, D.; Nagase, S.; Tokitoh, N., 1,2-Insertion Reactions of Alkynes into Ge–C Bonds of Arylbromogermylene, Dalton Trans., 10.1039/D0DT01223H, 49, 7189-7196, 2020.06.
11. Kazunobu Igawa, Yuuya Kawasaki, Sora Nozaki, Naoto Kokan, Katsuhiko Tomooka, Ozone Oxidation of Silylalkene
Mechanistic Study and Application for the Synthesis of Silacarboxylic Acid Derivatives, Journal of Organic Chemistry, 10.1021/acs.joc.9b03350, 85, 6, 4165-4171, 2020.03, The addition-type ozone oxidation of silylalkenes is a highly efficient reaction to provide synthetically versatile α-silylperoxy carbonyl compounds. To gain insight into the reaction mechanism, we performed a computational study, which revealed that the reaction proceeds via [1,2]-Brook rearrangement-type silyl migration of primary ozonide. In sharp contrast to the addition-type reactions, the ozone oxidation of α-alkoxysilylalkenes proceeds in a cleavage-type manner to afford excellent yields of silacarboxylic acid esters via the 1,3-cycloelimination of primary ozonide prior to 1,2-silyl migration..
12. Ryoma Masuda, Yuuya Kawasaki, Kazunobu Igawa, Yoshiyuki Manabe, Hiroshi Fujii, Nobuo Kato, Katsuhiko Tomooka, Junko Ohkanda, Copper-Free Huisgen Cycloaddition for the 14-3-3-Templated Synthesis of Fusicoccin-Peptide Conjugates, Chemistry - An Asian Journal, 10.1002/asia.202000042, 2020.01, Mid-sized molecules have emerged as an attractive chemical space and potentially provide a robust basis for the development of synthetic agents to control intracellular protein interactions. However, the limited cell permeability and chemical tractability of such agents remain to be addressed. We envisioned that target-templated synthesis of such mid-sized molecules might provide a solution. Here, we exploited a copper-free Huisgen cycloaddition for template synthesis using a peptide fragment containing a 4,8-diazacyclononyne (DACN) moiety and an azide-containing fusicoccin derivative in the presence or absence of recombinant 14-3-3ζ protein in vitro. Time-course changes in the yield of products demonstrated that the reaction was accelerated in the presence of 14-3-3 and one of the regioisomers was generated predominantly, supporting the template effect..
13. Fumi Tetsuo, Masaki Arioka, Koichi Miura, Misato Kai, Momoko Kubo, Kazunobu Igawa, Katsuhiko Tomooka, Fumi Takahashi-Yanaga, Fusanori Nishimura, Toshiyuki Sasaguri, Differentiation-inducing factor-1 suppresses cyclin D1-induced cell proliferation of MCF-7 breast cancer cells by inhibiting S6K-mediated signal transducer and activator of transcription 3 synthesis, Cancer Science, 10.1111/cas.14204, 110, 12, 3761-3772, 2019.12, Differentiation-inducing factor-1 (DIF-1) has been reported to inhibit the proliferation of various mammalian cells by unknown means, although some possible mechanisms of its action have been proposed, including the activation of glycogen synthase kinase-3 (GSK-3). Here, we report an alternative mechanism underlying the action of DIF-1 in human breast cancer cell line MCF-7, on which the effects of DIF-1 have not been examined previously. Intragastric administration of DIF-1 reduced the tumor growth from MCF-7 cells injected into a mammary fat pad of nude mice, without causing adverse effects. In cultured MCF-7, DIF-1 arrested the cell cycle in G0/G1 phase and suppressed cyclin D1 expression, consistent with our previous results obtained in other cell species. However, DIF-1 did not inhibit the phosphorylation of GSK-3. Investigating an alternative mechanism for the reduction of cyclin D1, we found that DIF-1 reduced the protein levels of signal transducer and activator of transcription 3 (STAT3). The STAT3 inhibitor S3I-201 suppressed cyclin D1 expression and cell proliferation and the overexpression of STAT3 enhanced cyclin D1 expression and accelerated proliferation. Differentiation-inducing factor-1 did not reduce STAT3 mRNA or reduce STAT3 protein in the presence of cycloheximide, suggesting that DIF-1 inhibited STAT3 protein synthesis. Seeking its mechanism, we revealed that DIF-1 inhibited the activation of 70 kDa and/or 85 kDa ribosomal protein S6 kinase (p70S6K/p85S6K). Inhibition of p70S6K/p85S6K by rapamycin also reduced the expressions of STAT3 and cyclin D1. Therefore, DIF-1 suppresses MCF-7 proliferation by inhibiting p70S6K/p85S6K activity and STAT3 protein synthesis followed by reduction of cyclin D1 expression..
14. Shoji Morishige, Fumi Takahashi-Yanaga, Shin Ishikane, Masaki Arioka, Kazunobu Igawa, Akihiro Kuroo, Katsuhiko Tomooka, Akira Shiose, Toshiyuki Sasaguri, 2,5-Dimethylcelecoxib prevents isoprenaline-induced cardiomyocyte hypertrophy and cardiac fibroblast activation by inhibiting Akt-mediated GSK-3 phosphorylation, Biochemical Pharmacology, 10.1016/j.bcp.2019.06.018, 168, 82-90, 2019.10, We previously reported that 2,5-dimethylcelecoxib (DM-celecoxib), a celecoxib derivative that is unable to inhibit cyclooxygenase-2, prevented cardiac remodeling by activating glycogen synthase kinase-3 (GSK-3) and prolonged the lifespan of heart failure mice with genetic dilated cardiomyopathy or transverse aortic constriction-induced left ventricular hypertrophy. However, it remained unclear how DM-celecoxib regulated structure and function of cardiomyocytes and cardiac fibroblasts involved in cardiac remodeling. In the present study, therefore, we investigated the effect of DM-celecoxib on isoprenaline-induced cardiomyocyte hypertrophy and cardiac fibroblast activation, because DM-celecoxib prevented isoprenaline-induced cardiac remodeling in vivo. DM-celecoxib suppressed isoprenaline-induced neonatal rat cardiomyocyte hypertrophy by the inhibition of Akt phosphorylation resulting in the activation of GSK-3 and the inhibition of β-catenin and mammalian target of rapamycin (mTOR). DM-celecoxib also suppressed the proliferation and the production of matrix metalloproteinase-2 and fibronectin of rat cardiac fibroblasts. Moreover, we found that phosphatase and tensin homolog on chromosome 10 (PTEN) could be a molecule to mediate the effect of DM-celecoxib on Akt. These results suggest that DM-celecoxib directly improves the structure and function of cardiomyocytes and cardiac fibroblasts and that this compound could be clinically useful for the treatment of β-adrenergic receptor-mediated maladaptive cardiac remodeling..
15. Nozomi Mihara, Yasuyuki Yamada, Hikaru Takaya, Yasutaka Kitagawa, Kazunobu Igawa, Katsuhiko Tomooka, Hiroshi Fujii, Kentaro Tanaka, Site-Selective Supramolecular Complexation Activates Catalytic Ethane Oxidation by a Nitrido-Bridged Iron Porphyrinoid Dimer, Chemistry - A European Journal, 10.1002/chem.201805580, 25, 13, 3369-3375, 2019.03, Development of supramolecular methods to further activate a highly reactive intermediate is a fascinating strategy to create novel potent catalysts for activation of inert chemicals. Herein, a supramolecular approach to enhance the oxidizing ability of a high-valent oxo species of a nitrido-bridged iron porphyrinoid dimer that is a known potent molecular catalyst for light alkane oxidation is reported. For this purpose, a nitrido-bridged dinuclear iron complex of porphyrin-phthalocyanine heterodimer 3
, which is connected through a fourfold rotaxane, was prepared. Heterodimer 3
catalyzed ethane oxidation in the presence of H
at a relatively low temperature. The site-selective complexation of 3
with an additional anionic porphyrin (TPPS
) through π–π stacking and electrostatic interactions afforded a stable 1:1 complex. It was demonstrated that the supramolecular post-synthetic modification of 3
enhances its catalytic activity efficiently. Moreover, supramolecular conjugates achieved higher catalytic ethane oxidation activity than nitrido-bridged iron phthalocyanine dimer, which is the most potent iron-oxo-based molecular catalyst for light-alkane oxidation reported so far. Electrochemical measurements proved that the electronic perturbation from TPPS
to 3
enhanced the catalytic activity..
16. Yuuya Kawasaki, Yuki Yamanaka, Yuki Seto, Kazunobu Igawa, Katsuhiko Tomooka, Synthesis of NMs-DACN
Small and hydrophilic click reaction device, Chemistry Letters, 10.1246/cl.190026, 48, 5, 495-497, 2019.01, Newly designed small and hydrophilic click reaction devices, NMs-4, 8-diazacyclononynes (NMs-DACNs), have been efficiently synthesized by a one-pot double Nicholas approach. NMs-DACNs react with azides smoothly under copper-free conditions and show higher water solubility than that of previously developed NTs-DACNs..
17. Jun-ichi Hayashi, Kazuhiro Uehara, Yusuke Ano, Yuuya Kawasaki, Kazunobu Igawa, Katsuhiko Tomooka , SYNTHESIS AND STEREOCHEMICAL ANALYSIS OF DYNAMIC PLANAR CHIRAL NINE-MEMBERED DIALLYLIC AMIDE: SIGNIFICANT SUBSTITUENT EFFECT ON STEREOCHEMICAL STABILITY, Heterocycles, 10.3987/COM-18-S(F)92, 99, 2019.01.
18. Yasuyuki Yamada, Kentaro Morita, Nozomi Mihara, Kazunobu Igawa, Katsuhiko Tomooka, Kentaro Tanaka, Catalytic methane oxidation by a supramolecular conjugate based on a μ-nitrido-bridged iron porphyrinoid dimer, New Journal of Chemistry, 10.1039/c9nj02210d, 43, 29, 11477-11482, 2019.01, Catalytic methane oxidation was conducted using a μ-nitrido-bridged dinuclear iron complex of a four-fold rotaxane heterodimer of a porphyrin and a phthalocyanine. Extension of the π-stacked structure of the four-fold rotaxane-based μ-nitrido-bridged iron porphyrinoid dimer by supramolecular complexation with an additional tetraanionic porphyrin apparently increased the methane conversion ability..
19. Kazunobu Igawa, Yuuya Kawasaki, Yusuke Ano, Takeru Kashiwagi, Kouhei Ogawa, Jun Ichi Hayashi, Ryota Morita, Yukari Yoshioka, Kazuhiro Uehara, Katsuhiko Tomooka, Preparation of enantioenriched chiral organic molecules by dynamic asymmetric induction from a outer chiral source, Chemistry Letters, 10.1246/cl.190170, 48, 7, 726-729, 2019.01, To obtain enantioenriched chiral organic molecules, numerous optical resolution and asymmetric synthetic methods have been developed to date. Herein, we introduce a new approach termed dynamic asymmetric induction (DYASIN) for the preparation of enantioenriched chiral molecules based on the stereocontrol of dynamic chiral molecules (DYCMs) using an outer chiral source (OCS). DYASIN makes it possible to obtain the enantioenriched form of dynamic chiral molecules from their racemic form without bond cleavage or bond formation. The thus-obtained enantioenriched molecules can be readily converted into a variety of chiral molecules with stable stereochemistries, without any loss of enantiomeric purity..
20. Kazuteru Usui, Kosuke Yamamoto, Yuhei Ueno, Kazunobu Igawa, Ryusuke Hagihara, Toshinobu Masuda, Akio Ojida, Satoru Karasawa, Katsuhiko Tomooka, Go Hirai, Hiroshi Suemune, Internal-Edge-Substituted Coumarin-Fused [6]Helicenes
Asymmetric Synthesis, Structural Features, and Control of Self-Assembly, Chemistry - A European Journal, 10.1002/chem.201803270, 24, 55, 14617-14621, 2018.10, π-Conjugated helicenes containing heteroatoms have attracted significant attention due to their diverse chemical and electronic structures, as well as tunable physical properties. It was rationally anticipated that the self-assembly of coumarin-fused helicenes would be controlled by the effects of a substituent on the internal edge of the helix. Here, this work reports the efficient syntheses of coumarin-fused helicenes 1 a,b (R=Ph, Me), and the enantioselective synthesis of 1 a (R=Ph) by chiral AuI-catalyzed hydroarylation. The helical structure of 1 was unambiguously determined by X-ray crystallography. Of particular note, the enantiomerically pure crystal of 1 a adopted a one-dimensional columnar structure based on π–π stacking interactions, as expected. Furthermore, a significant difference between the fluorescence quantum yields of the enantiomerically pure form and racemate of 1 a was observed..
21. Sachie Arae, Shota Beppu, Takahiro Kawatsu, Kazunobu Igawa, Katsuhiko Tomooka, Ryo Irie, Asymmetric Synthesis of Axially Chiral Benzocarbazole Derivatives Based on Catalytic Enantioselective Hydroarylation of Alkynes, Organic Letters, 10.1021/acs.orglett.8b01945, 20, 16, 4796-4800, 2018.08, A new synthetic approach to novel axially chiral benzocarbazole derivatives based on the highly enantioselective intramolecular hydroarylation (94-96% ee) of linked alkyne-indole systems by using the prevalent chiral base catalyst, cinchonidine or cinchonine, under unprecedented transition-metal-free conditions is described. The process is considered to involve chiral base catalysis for enantioselective transformation of the alkyne part to a reaction intermediate with an axially chiral vinylidene o-quinone methide (VQM) functionality, which subsequently effects stereospecific cyclization with the tethered indole moiety..
22. Tomohiro Meguro, Suguru Yoshida, Kazunobu Igawa, Katsuhiko Tomooka, Takamitsu Hosoya, Transient Protection of Organic Azides from Click Reactions with Alkynes by Phosphazide Formation, Organic Letters, 10.1021/acs.orglett.8b01692, 20, 13, 4126-4130, 2018.07, A method for protecting organic azides from click reactions with alkynes is reported. Treatment of azides with Amphos affords phosphazides, which are stable under click reaction conditions and are easily converted back to azides by treatment with elemental sulfur. Thus, the method allows for facile modification of azide compounds via site-selective click reactions..
23. Kouhei Machida, Yuki Yoshida, Kazunobu Igawa, Katsuhiko Tomooka, Efficient approach to medium-sized cyclic molecules containing (E)-Alkene via z to e photochemical isomerization in the presence of AgNO3-impregnated silica gel, Chemistry Letters, 10.1246/cl.170937, 47, 2, 186-188, 2018.01, Efficient synthesis of medium-sized cyclic molecules containing an (E)-alkene was performed via the highly (E)selective photochemical isomerization of the (Z)-isomer, facilitated by AgNO3-impregnated silica gel..
24. Sachie Arae, Masaki Furusawa, Shota Beppu, Kazunobu Igawa, Katsuhiko Tomooka, Ryo Irie, Vinylidene ortho-quinone methides
Unique chiral reaction intermediates in catalytic asymmetric synthesis, Chimia, 10.2533/chimia.2018.892, 72, 12, 892-899, 2018.01, Vinylidene ortho-quinone methides (VQMs) are one-carbon elongated homologues of ortho-quinone methides (QMs), well-known as useful reaction intermediates in organic transformations. These related quinone methides are quite distinct in terms of stereochemistry. Namely, VQMs are characterized by an exocyclic allenyl ketone unit merged with a dearomatized ring system and thus, can be rendered axially chiral by locating a substituent properly at the terminal methylene group of the allene moiety. It should be also noted that VQMs are tautomers of ortho-ethynylphenols and these isomeric species are correlated through a proton-shift (tautomerization). Focusing on these stereochemical and structural features, we have pursued the development of unprecedented asymmetric reactions involving enantioenriched VQM intermediates generated by chiral-basecatalyzed tautomerization of the ethynylphenol precursors. Indeed, commonly used chiral base catalysts such as cinchonine (CN) and cinchonidine (CD) have been successfully demonstrated to be effective to this end. In this account, we wish to briefly describe our recent studies on the asymmetric syntheses of optically active indeno[1,2-c]chromenes, benzofuro[3,2-b]indeno[1,2-c]chromenes, and benzo[a]carbazoles, based on the catalytic enantioselective generation of VQMs with CN or CD and the stereocontrolled intramolecular follow-up cyclization with tethered alkynes, benzofurans, and indoles, respectively..
25. Shota Beppu, Sachie Arae, Masaki Furusawa, Kosuke Arita, Hitoshi Fujimoto, Michinori Sumimoto, Tatsushi Imahori, Kazunobu Igawa, Katsuhiko Tomooka, Ryo Irie, Stereoselective Intramolecular Dearomatizative [4+2] Cycloaddition of Linked Ethynylnaphthol–Benzofuran Systems, European Journal of Organic Chemistry, 10.1002/ejoc.201701481, 2017, 46, 6914-6918, 2017.12, A base-catalyzed stereoselective intramolecular dearomatizative [4+2] cycloaddition of o-phenylene-linked ethynylnaphthol–benzofuran systems was explored. In this reaction, we presume the involvement of electrophilic vinylidene o-quinone methides (4π), which add across the electron-rich furan double bonds (2π) to produce elaborate, fused oxa-polyheterocyclic frameworks with consecutive quaternary and tertiary asymmetric carbon atoms as single diastereomers. The catalytic and enantioselective synthesis of these chiral fused polyheterocyclic structures is also feasible with the use of a prevalent cinchonidine or cinchonine chiral base..
26. Suguru Yoshida, Keita Shimizu, Keisuke Uchida, Yuki Hazama, Kazunobu Igawa, Katsuhiko Tomooka, Takamitsu Hosoya, Construction of Condensed Polycyclic Aromatic Frameworks through Intramolecular Cycloaddition Reactions Involving Arynes Bearing an Internal Alkyne Moiety, Chemistry - A European Journal, 10.1002/chem.201704345, 23, 61, 15332-15335, 2017.11, Facile synthetic methods for condensed polycyclic aromatic compounds via aryne intermediates are reported. The generation of arynes bearing a (3-arylpropargyl)oxy group from the corresponding o-iodoaryl triflate-type precursors efficiently afforded arene-fused oxaacenaphthene derivatives, which were formed through intramolecular [2+4] cycloaddition. Extending the method to the generation of arynes bearing a 1,3-diyne moiety led to a continuous generation of naphthalyne intermediate through the hexadehydro Diels–Alder reaction involving the aryne triple bond. This novel type of aryne-relay chemistry enabled the synthesis of a unique aminoarylated oxaacenaphthene derivative and highly ring-fused anthracene derivatives..
27. Kazunobu Igawa, Akihiro Kuroo, Daisuke Yoshihiro, Yuki Yamanaka, Katsuhiko Tomooka, Synthesis of Stereoselectively Functionalized Silacyclopentanes, Synlett, 10.1055/s-0036-1590826, 28, 18, 2445-2448, 2017.11, An efficient approach to a variety of chiral silacyclopentanes having silicon stereogenic center based on the stereospecific transformations of C4 carbon stereogenic center of silacyclopentenols by Mitsunobu reaction or Tsuji-Trost reaction has been developed. The thus obtained substitution products can be converted into novel silacyclopentane triols, amines, and carboxylic acids in stereospecific manner..
28. Masaki Arioka, Fumi Takahashi-Yanaga, Momoko Kubo, Kazunobu Igawa, Katsuhiko Tomooka, Toshiyuki Sasaguri, Anti-tumor effects of differentiation-inducing factor-1 in malignant melanoma
GSK-3-mediated inhibition of cell proliferation and GSK-3-independent suppression of cell migration and invasion, Biochemical Pharmacology, 10.1016/j.bcp.2017.05.004, 138, 31-48, 2017.08, Differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium discoideum strongly inhibits the proliferation of various mammalian cells through the activation of glycogen synthase kinase-3 (GSK-3). To evaluate DIF-1 as a novel anti-cancer agent for malignant melanoma, we examined whether DIF-1 has anti-proliferative, anti-migratory, and anti-invasive effects on melanoma cells using in vitro and in vivo systems. DIF-1 reduced the expression levels of cyclin D1 and c-Myc by facilitating their degradation via GSK-3 in mouse (B16BL6) and human (A2058) malignant melanoma cells, and thereby strongly inhibited their proliferation. DIF-1 suppressed the canonical Wnt signaling pathway by lowering the expression levels of transcription factor 7-like 2 and β-catenin, key transcription factors in this pathway. DIF-1 also inhibited cell migration and invasion, reducing the expression of matrix metalloproteinase-2; however, this effect was not dependent on GSK-3 activity. In a mouse lung tumor formation model, repeated oral administrations of DIF-1 markedly reduced melanoma colony formation in the lung. These results suggest that DIF-1 inhibits cell proliferation by a GSK-3-dependent mechanism and suppresses cell migration and invasion by a GSK-3-independent mechanism. Therefore, DIF-1 may have a potential as a novel anti-cancer agent for the treatment of malignant melanoma..
29. Ai Fujita, Fumi Takahashi-Yanaga, Sachio Morimoto, Tatsuya Yoshihara, masaki arioka, Kazunobu Igawa, Katsuhiko Tomooka, Sumio Hoka, Toshiyuki Sasaguri, 2,5-Dimethylcelecoxib prevents pressure-induced left ventricular remodeling through GSK-3 activation, Hypertension Research, 10.1038/hr.2016.122, 40, 2, 130-139, 2017.02, Glycogen synthase kinase-3 (GSK-3) is a crucial regulator of cardiac hypertrophy. We previously reported that 2,5-dimethylcelecoxib (DM-celecoxib), a celecoxib derivative unable to inhibit cyclooxygenase-2, prevented cardiac remodeling by activating GSK-3, resulting in lifespan prolongation in a mouse model of genetic dilated cardiomyopathy. In the present study, we investigated whether DM-celecoxib can also prevent pressure-induced cardiac remodeling and heart failure, elicited by transverse aortic constriction (TAC). Before testing the effects of DM-celecoxib, we compared the effects of TAC on the hearts of wild-type and GSK-3β hetero-deficient (GSK-3β+/-) mice to determine the role of GSK-3 in cardiac remodeling and heart failure. GSK-3β+/- mouse hearts exhibited more severe hypertrophy, which was characterized by accelerated interstitial fibrosis, than wild-type mouse hearts after TAC, suggesting that reduced GSK-3β activity aggravates pressure-induced left ventricular remodeling. We subsequently examined the effects of DM-celecoxib on TAC-induced cardiac remodeling. DM-celecoxib inhibited left ventricular systolic functional deterioration, and prevented left ventricular hypertrophy and fibrosis. It also activated GSK-3α and β by inhibiting Akt, suppressing the activity of β-catenin and nuclear factor of activated T-cells and thereby decreasing the expression of the Wnt/β-catenin target gene products fibronectin and matrix metalloproteinase-2. These results suggest that DM-celecoxib is clinically useful for treating pressure-induced heart diseases..
30. Kazunobu Igawa, Shin Aoyama, Yuuya Kawasaki, Takeru Kashiwagi, Yuki Seto, Runyan Ni, Naoto Mitsuda, Katsuhiko Tomooka, One-Pot Synthesis of Versatile Buckle Units for Click Chemistry: 4,8-Diazacyclononynes (DACNs), Synlett, 10.1055/s-0036-1588839, 28, 16, 2110-2114, 2017.01, Newly designed buckle units for copper-free click chemistry: 4,8-diazacyclononynes (DACNs) were efficiently synthesized with a one-pot procedure from commercially available 2-butyne-1,4-diol. The synthesized DACNs possess versatile connectors for the introduction of functional units and exhibit high click reactivity..
31. Issei Egashira, Fumi Takahashi-Yanaga, Risa Nishida, masaki arioka, Kazunobu Igawa, Katsuhiko Tomooka, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Yusaku Nakabeppu, Takanari Kitazono, Toshiyuki Sasaguri, Celecoxib and 2,5-dimethylcelecoxib inhibit intestinal cancer growth by suppressing the Wnt/β-catenin signaling pathway, Cancer Science, 10.1111/cas.13106, 108, 1, 108-115, 2017.01, We previously reported that celecoxib, a selective COX-2 inhibitor, strongly inhibited human colon cancer cell proliferation by suppressing the Wnt/β-catenin signaling pathway. 2,5-Dimethylcelecoxib (DM-celecoxib), a celecoxib analog that does not inhibit COX-2, has also been reported to have an antitumor effect. In the present study, we elucidated whether DM-celecoxib inhibits intestinal cancer growth, and its underlying mechanism of action. First, we compared the effect of DM-celecoxib with that of celecoxib on the human colon cancer cell lines HCT-116 and DLD-1. 2,5-Dimethylcelecoxib suppressed cell proliferation and inhibited T-cell factor 7-like 2 expression with almost the same strength as celecoxib. 2,5-Dimethylcelecoxib also inhibited the T-cell factor-dependent transcription activity and suppressed the expression of Wnt/β-catenin target gene products cyclin D1 and survivin. Subsequently, we compared the in vivo effects of celecoxib and DM-celecoxib using the Mutyh−/− mouse model, in which oxidative stress induces multiple intestinal carcinomas. Serum concentrations of orally administered celecoxib and DM-celecoxib elevated to the levels enough to suppress cancer cell proliferation. Repeated treatment with celecoxib and DM-celecoxib markedly reduced the number and size of the carcinomas without showing toxicity. These results suggest that the central mechanism for the anticancer effect of celecoxib derivatives is the suppression of the Wnt/β-catenin signaling pathway but not the inhibition of COX-2, and that DM-celecoxib might be a better lead compound candidate than celecoxib for the development of novel anticancer drugs..
32. Katsuhiko Tomooka, Chemistry of planar chiral medium-sized heterocycles, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.75.449, 75, 5, 449-457, 2017.01, Nine-membered E,Z-diallylic heterocycles 1 and [7]-orthocyclphenes 2 exhibit planar chirality at ambient temperature. Their stereochemical stabilities are highly dependent on substituent R1 on the E-Alkene, embedded heteroatom X in the ring, and ring size. Their planar chirality can be transformed into carbon central chirality without loss of enantiopurity. Therefore, they are useful chiral building blocks for biologically active chiral molecules and precursors for chiral reagents. The enantioenriched forms of 1 and 2 are available by optical resolution of racemate, and asymmetric synthesis based on enantioselective cyclization. Planar chiral dialkoxysilane 32 and ketone 33 were also developed..
33. Nozomi Mihara, Yasuyuki Yamada, Hikaru Takaya, Yasutaka Kitagawa, Shin Aoyama, Kazunobu Igawa, Katsuhiko Tomooka, Kentaro Tanaka, Oxygen Reduction to Water by a Cofacial Dimer of Iron(III)–Porphyrin and Iron(III)–Phthalocyanine Linked through a Highly Flexible Fourfold Rotaxane, Chemistry - A European Journal, 10.1002/chem.201700082, 23, 31, 7508-7514, 2017.01, A μ-oxo-dinuclear iron complex of a supramolecular porphyrin–phthalocyanine conjugate was synthesized and its catalytic electrochemical oxygen reduction properties were investigated. In the conjugate, porphyrin and phthalocyanine units were connected to form a cofacial dimeric structure through a flexible fourfold rotaxane linkage, which was advantageous for accommodating small substrates between the iron centers. The conjugate showed efficient catalytic properties, at more positive potentials than those of other reported dinuclear porphyrinoid iron complexes, to selectively afford water through a four-electron reduction process..
34. Sachie Arae, Takaaki Mori, Takahiro Kawatsu, Daiki Ueda, Yusuke Shigeta, Nobutsugu Hamamoto, Hitoshi Fujimoto, Michinori Sumimoto, Tatsushi Imahori, Kazunobu Igawa, Katsuhiko Tomooka, Tharmalingam Punniyamurthy, Ryo Irie, Synthesis and stereochemical properties of chiral hetero[7]helicenes structured by a benzodiheterole ring core, Chemistry Letters, 10.1246/cl.170410, 46, 8, 1214-1216, 2017.01, A new hetero[7]helicene 1NN structured by a diazabenzodiheterole (pyrroloindole) ring core was successfully synthesized by catalytic domino cyclodehydrogenation with Pd(OAc)2 and O2 as the key step. Significantly, 1NN was stereochemically stable at room temperature and could be subjected to optical resolution by chiral HPLC. Furthermore, kinetic analysis of 1NN and DFT calculations on its variants revealed that the stereo-chemical stability of the benzodiheterole-based helicenes was highly dependent on not only the heteroaromatic ring component but also on the N-substituent of the pyrrole ring unit..
35. Kazunobu Igawa, Kouhei Machida, Kyouhei Noguchi, Kazuhiro Uehara, Katsuhiko Tomooka, Synthesis and Stereochemical Analysis of Planar-Chiral (E)-4-[7]Orthocyclophene, Journal of Organic Chemistry, 10.1021/acs.joc.6b01799, 81, 23, 11587-11593, 2016.12, An efficient synthesis of (E)-4-[7]orthocyclophene (E)-1 via photochemical isomerization of (Z)-1 has been achieved. The key intermediate (Z)-1 was synthesized from commercially available 2-(hydroxymethyl)benzenepropanol (3) in five steps: (i) group-selective Mitsunobu reaction with CH2=CHCH2CH(SO2Ph)2, (ii) oxidation of alcohol, (III) olefination, (iv) RCM, and (v) removal of sulfones in an overall yield of 73%. The photochemical isomerization of (Z)-1 was efficiently performed in the presence of AgNO3-impregnated silica gel (AgNO3/SiO2). The resulting (E)-1 shows dynamic planar chirality at rt. Enantioenriched (E)-1 was prepared by the HPLC separation of enantiomers using a chiral stationary phase, and the absolute stereochemistry was determined by X-ray diffraction analysis of the Pt-coordinated crystalline derivative. The planar chirality of (E)-1 can be converted into the central chirality of carbon; e.g., the oxidation of (R)-(E)-1 using DMDO provided epoxide (8S,9S)-9 in a stereospecific manner. Furthermore, the Lewis acid-promoted reaction of (8S,9S)-9 afforded a unique tricyclic compound (8S,9S)-10 in an excellent yield and in a stereospecific manner..
36. Kosuke Yamamoto, Takashi Shimizu, Kazunobu Igawa, Katsuhiko Tomooka, Go Hirai, Hiroshi Suemune, Kazuteru Usui, Rational Design and Synthesis of [5]Helicene-Derived Phosphine Ligands and Their Application in Pd-Catalyzed Asymmetric Reactions, Scientific Reports, 10.1038/srep36211, 6, 2016.11, A series of novel optically active [5]helicene-derived phosphine ligands (L1, with a 7,8-dihydro[5]helicene core structure- and L2, with a fully aromatic [5]helicene core structure) were synthesized. Despite their structural similarities, L1 and L2 exhibit particularly different characteristics in their use as chiral ligands. L1 was highly effective in the asymmetric allylation of indoles with 1,3-diphenylallyl acetate (up to 99% ee), and in the etherification of alcohols (up to 96% ee). In contrast, L2 was highly effective in the stereocontrol of helical chirality in Suzuki-Miyaura coupling (SMC) reaction (up to 99% ee). Density functional theory analysis was employed to propose a model that accounts for the origin of the enantioselectivity in these reactions..
37. Kazunobu Igawa, Daisuke Yoshihiro, Yusuke Abe, Katsuhiko Tomooka, Enantioselective Synthesis of Silacyclopentanes, Angewandte Chemie - International Edition, 10.1002/anie.201511728, 55, 19, 5814-5818, 2016.05, A variety of functionalized silacyclopentanes were synthesized by highly enantioselective β-eliminations of silacyclopentene oxides followed by stereospecific transformations. The reaction mechanism of the β-elimination was elucidated by DFT calculations. An in vitro biological assay with an oxy-functionalized silacyclopentane showed substantial binding to a serotonin receptor protein..
38. Kazunobu Igawa, Daisuke Yoshihiro, Yusuke Abe, Katsuhiko Tomooka, Enantioselective Synthesis of Silacyclopentanes, Angew. Chem. Int. Ed., DOI: 10.1002/anie.201511728, 55, 5814-5818, 2016.04, A variety of functionalized silacyclopentanes were synthesized by highly enantioselective β‐eliminations of silacyclopentene oxides followed by stereospecific transformations. The reaction mechanism of the β‐elimination was elucidated by DFT calculations. An in vitro biological assay with an oxy‐functionalized silacyclopentane showed substantial binding to a serotonin receptor protein..
39. Suguru Yoshida, Takahisa Yano, Yoshitake Nishiyama, Yoshihiro Misawa, Masakazu Kondo, Takeshi Matsushita, Kazunobu Igawa, Katsuhiko Tomooka, Takamitsu Hosoya, Thiazolobenzyne
A versatile intermediate for multisubstituted benzothiazoles, Chemical Communications, 10.1039/c6cc05112j, 52, 75, 11199-11202, 2016.01, Thiazolobenzyne, which is a benzyne species fused with a thiazole ring, was efficiently generated via an iodine-magnesium exchange reaction of an ortho-iodoaryl triflate-type precursor using a trimethylsilylmethyl Grignard reagent as an activator. A wide range of arynophiles reacted efficiently with the thiazolobenzynes generated by this method to afford various multisubstituted benzothiazoles..
40. Suguru Yoshida, Takahisa Yano, Yoshihiro Misawa, Yasuyuki Sugimura, Kazunobu Igawa, Shigeomi Shimizu, Katsuhiko Tomooka, Takamitsu Hosoya, Direct Thioamination of Arynes via Reaction with Sulfilimines and Migratory N-Arylation, J. Am. Chem. Soc., 10.1021/jacs.5b10557, 137, 44, 14071-14074, 2015.09.
41. Takhiro Kawatsu, Hiroki Tokushima, Yuya Takedomi, Tatsushi Imahori, Kazunobu Igawa, Katsuhiko Tomooka, Ryo Irie, Synthesis, stereochemical characteristics, and coordination behavior of 2,2’-binaphthyl-1,1’-biisoquinoline as a new axially chiral bidentate ligand, ARKIVOC,, 2015, 4, 161-175, 2015.07.
42. Takahiro Kawatsu, Hiroki Tokushima, Yuya Takedomi, Tatsushi Imahori, Kazunobu Igawa, Katsuhiko Tomooka, Ryo Irie, Synthesis, stereochemical characteristics, and coordination behavior of 2,2'-binaphthyl-1,1'-biisoquinoline as a new axially chiral bidentate ligand, Arkivoc, 10.3998/ark.5550190.p009.069, 2015, 4, 161-175, 2015.07, We describe the synthesis, stereochemical characteristics, and coordination behavior of 2,2'-binaphtyl-1,1'-biisoquinoline (BINIQ), a new axially chiral bidentate ligand. BINIQ was obtained in a racemic form by the diastereoselective Ullmann coupling of 1-(2-iodonaphthalen-1-yl)isoquinoline, which was prepared by the regioselective C-H iodination of 1-(1-naphthyl)isoquinoline. BINIQ has three chiral biaryl axes α and γ at the two naphthylisoquinoline and β at the 2,2'-binaphthyl sites and their relative configuration (αRaβRa , γa ) in solid state was confirmed by X-ray diffraction analysis. The naphthyl-isoquinoline axes α and γ were proven rigid enough in solution to allow for optical resolution by a chiral HPLC method and a solution of the optically pure BINIQ (98% ee) in chloroform-d did not result in racemization while standing at room temperature for 24 h. On the other hand, the 2,2'-binaphthyl axis is stereochemically labile and readily alternates between βRa and βSa at room temperature. Accordingly, (αRa a γa )- and (αRa a ,γRa)-BINIQ are in equilibrium in solution with the former stereoisomer being dominant, though the latter is suitable as a bidentate ligand. Notably, this dynamic stereochemical behavior enabled BINIQ to readily give the relative configuration (αRa a ,γRa ) upon coordination to a copper(I) ion at room temperature..
43. Kazunobu Igawa, Nobumasa Ichikawa, Yusuke Ano, Keisuke Katanoda, Masato Ito, Toshiyuki Akiyama, Katsuhiko Tomooka, Catalytic Enantioselective Synthesis of Planar Chiral Cyclic Amides Based on Pd-catalyzed Asymmetric Allylic Substitution Reaction, J. Am. Chem. Soc., 10.1021/jacs.5b04340, 137, 23, 7294-7297, 2015.06.
44. Kazunobu Igawa, Shouji Miyasaka, Shougo Motomura, Katsuhiko Tomooka, Planar Chiral Dialkoxysilane: Introduction of Inherent Chirality and High Reactivity in Conventional Achiral Alkene, Chem. Eur. J., 10.1002/chem.201402434, 20, 7598-7602, 2014.05.
45. Fumi Takahashi, Yoshihara Tatsuya, Kentaro Jingushi, Kazunobu Igawa, Katsuhiko Tomooka, Yutaka Watanabe, Sachio Morimoto, Yoshimichi Nakatsu, Teruhisa Tsuzuki, Yusaku Nakabeppu, Toshiyuki Sasaguri, DIF-1 inhibits tumor growth in vivo reducing phosphorylation of GSK-3b and expressions of cyclin D1 and TCF7L2 in cancer model mice, Biochem. Pharm., 10.1016/j.bcp.2014.03.006, 89, 340-348, 2014.03.
46. Kazunobu Igawa, Takeshi Kawabata, Runyan Ni, Katsuhiko Tomooka, Synthesis, Structural Analysis, and Reaction of 3-Aza-5-[7]orthocyclophyne, Chem. Lett, 10.1246/cl.130735, 42, 1374-1376, 2013.11.
47. Takashi Kamachi, Ken-ichi Shimizu, Kazunobu Igawa, Katsuhiko Tomooka, Kazunari Yoshizawa, Oxidation of Silanes to Silanols on Pd Nanoparticles: H2 Desorption Accelerated by Surface Oxyge, J. Phys. Chem. C, 10.1021/jp408269s, 117, 22967-22973, 2013.10.
48. Masaki Furusawa, Kosuke Arita, Tatsushi Imahori, Kazunobu Igawa, Katsuhiko Tomooka, Ryo Irie, Base-catalyzed Schmittel Cycloisomerization of o-Phenylenediyne-linked Bis(arenol)s to Indeno[1,2-c]chromenes, Tetrahedron Lett., 10.1016/j.tetlet.2013.10.080, 54, 7107-7110, 2013.10.
49. Masaki Furusawa, Tatsushi Imahori, Kazunobu Igawa, Katsuhiko Tomooka, Ryo Irie, Palladium-catalyzed Tandem Cyclodehydrogenation of o-Phenilenediyne-linked Bis(arenol)s to Produce Benzodifuran-containing Condensed Heteroaromatic Ring Systems, Chem. Lett., 10.1246/cl.130411, 42, 1134-1136, 2013.06.
50. Suguru Yoshida, Kazunobu Igawa, Katsuhiko Tomooka, Nucleophilic Substitution Reaction at the Nitrogen of Arylsulfonamides with Phosphide Anion, J. Am. Chem. Soc., 10.1021/ja309642r, 134, 19358-19361, 2012.11.
51. Kazunobu Igawa, Daisuke Yoshihiro, Nobumasa Ichikawa, Naoto Kokan, Katsuhiko Tomooka, Catalytic Enantioselective Synthesis of Alkenylhydrosilanes, Angew. Chem. Int. Ed., 10.1002/anie.201207361, 51, 12745-12748, 2012.11.
52. Katsuhiko Tomooka, Chisato Iso, Kazuhiro Uehara, Masaki Suzuki, Rie Nishikawa-Shimono, Kazunobu Igawa, Planar-Chiral [7]Orthocyclophanes, Angew. Chem. Int. Ed., 10.1002/anie.201204484, 51, 10355-10358, 2012.09.
53. Irie, R.; Tanoue, A.; Urakawa, S.; Imahori, R.; Igawa, K.; Matsumoto, T.; Tomooka, K.; Kikuta, S.; Uchida, T.; Katsuki, K., Synthesis and Stereochemical Behavior of a New Chiral Furano[7]helicene, Chem. Lett., 10.1246/cl.2011.1343, 40, 12, 1343-1345, 2011.12.
54. Kawasaki, Y.; Ishikawa, Y.; Igawa, K.; Tomooka, K., Directing Group-Controlled Hydrosilylation: Regioselective Functionalization of Alkyne, J. Am. Chem. Soc., 10.1021/ja209553f, 133, 20712-20715, 2011.12, アルキンの変換法として重要なヒドロシリル化反応について,従来は困難であった「反応の位置制御」の問題を解決した.具体的には,分子内に配向基を導入することでヒドロシリル化反応を触媒する白金錯体の位置を制御し,その結果としての生成物の位置制御を行うという新手法を開発した.本法により,精密有機合成化学において重要な非対称アルケニルシランの効率的合成が初めて可能となった..
55. Katsuhiko Tomooka, Masaki Suzuki, Maki Shimada, Runyan Ni, Kazuhiro Uehara, Erratum
Stereoselective multimodal transformations of planar chiral 9-membered diallylic amides (Organic Letters), Organic letters, 10.1021/ol2025873, 13, 21, 2011.11.
56. Tomooka, K.; Suzuki, M.; Shimada, M.; Ni, R.; Uehara, K., Stereoselective Multimodal Transformations of Planar Chiral 9-Membered Diallylic Amides, Organic Lett., 10.1021/ol202009x, 13, 18, 4926–4929, 2011.08.
57. Xueli Fan, Fumi Takahashi-Yanaga, Sachio Morimoto, Dong Yun Zhan, Kazunobu Igawa, Katsuhiko Tomooka, Toshiyuki Sasaguri, Celecoxib and 2,5-dimethyl-celecoxib prevent cardiac remodeling inhibiting akt-mediated signal transduction in an inherited dilated cardiomyopathy mouse model, Journal of Pharmacology and Experimental Therapeutics, 10.1124/jpet.111.179325, 338, 1, 2-11, 2011.07, Celecoxib, a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug, has been shown to inhibit Akt and prevent cardiac remodeling in aortic banding-induced failing heart in mice. However, it may be difficult to use celecoxib for the treatment of heart failure because of thromboembolic adverse reactions. Since 2,5-dimethyl (DM)-celecoxib, a derivative unable to inhibit COX-2, has been also reported to inhibit Akt, we attempted to examine whether DM-celecoxib retains the ability to prevent cardiac remodeling and improve cardiac functions using a mouse model of inherited dilated cardiomyopathy (DCM). DM-celecoxib as well as celecoxib administered daily for 4 weeks inhibited Akt and subsequent phosphorylation of glycogen synthase kinase-3β and mammalian target of rapamycin. Furthermore, both celecoxib and DM-celecoxib inhibited the activities of nuclear factor of activated T cell and -catenin and the expression of TCF7L2 (T-cell-specific transcriptional factor-7L2) and c-Myc, downstream mediators related to cardiac hypertrophy. Functional and morphological measurements showed that these compounds improved left ventricular systolic functions (ejection fraction: vehicle, 34.7 ± 3.9%; 100 mg/kg celecoxib, 50.3 ± 1.1%, p < 0.01; 100 mg/kg DM-celecoxib, 49.8 ± 0.8%, p < 0.01), which was also evidenced by the decrease in β-myosin heavy chain and B-type natriuretic peptide, and prevented hypertrophic cardiac remodeling (heart/body weight ratio: vehicle, 10.4 ± 0.7 mg/g; 100 mg/kg celecoxib, 8.0 ± 0.3 mg/g, p < 0.01; 100 mg/kg DM-celecoxib, 8.2 ± 0.1 mg/g, p < 0.05). As a consequence, both compounds improved the survival rate (vehicle, 45%; 100 mg/kg celecoxib, 75%, p < 0.05; 100 mg/kg DM-celecoxib, 70%, p < 0.05). These results suggested that not only celecoxib but also DM-celecoxib prevents cardiac remodeling and reduces mortality in DCM through a COX-2-independent mechanism involving Akt and its downstream mediators..
58. Tomooka, K.; Inoue, H.; Igawa, K., Synthesis and Stereochemical Behavior of (E)-Cyclononene Derivatives, Chemistry Letters, 10.1246/cl.2011.591, 40, 6, 591-593, 2011.06.
59. Fan, X.; Takahashi-Yanaga, F.; Morimoto, S.; Zhan, D-Y.; Igawa, K.; Tomooka, K.; Sasaguri S., Celecoxib and 2,5-dimethyl-celecoxib prevent cardiac remodeling inhibiting Akt-mediated signal transduction in an inherited DCM mouse model, The Journal of Pharmacology and Experimental Therapeutics, doi:10.1124/jpet.111.179325., 1, 338, 2-11, 2011.05.
60. Igawa, K.; Kawasaki, Y; Tomooka, K., Addition-type Oxidation of Silylalkene using Ozone: An Efficient Approach for Acyloin and Its Derivatives, Chemistry Letters, 10.1246/cl.2011.233, 40, 3, 233-235, 2011.02.
61. Tomooka, K.; Ezawa, T.; Inoue, H.; Uehara, K.; Igawa, K., Dynamic Chirality of (E)-5-Cyclononen-1-one and its Enolate, J. Am. Chem. Soc., 10.1021/ja1092375, 2011.01.
62. Katsuhiko Tomooka, Maki Shimada, Kazuhiro Uehara, Masato Ito, A unique functional group transformation of planar chiral diolefinic organonitrogen cycles utilizing PtCl2(2,4,6-trimethylpyridine) Complexes, Organometallics, 10.1021/om1009704, 29, 24, 6632-6635, 2010.12, The planar chiral diolefinic organonitrogen cycles 1 underwent stereospecific and group-selective olefin exchange with 3 to give 4, whose molecular structure was characterized on the basis of NMR and X-ray diffraction. The bonded (E)-olefin moieties in 4 were robust enough to allow untouched (Z)-olefin to undergo epoxidation and hydrogenation to give the corresponding PtCl2(n2-olefin) complexes, whose treatment with PPh 3 smoothly liberated their olefinic parts, which would be otherwise difficult to synthesize..
63. Tomooka, K.; Shimada, M.; Uehara, K.; Ito, M., A Unique Functional Group Transformation of Planar Chiral Diolefinic Organonitrogen Cycles Utilizing PtCl2(2,4,6-trimethylpyridine) Complexes, Organometallics, 29, 24, 6632–6635, 2010.11.
64. Katsuhiko Tomooka, Kazuhiro Uehara, Rie Nishikawa, Masaki Suzuki, Kazunobu Igawa, Enantioselective synthesis of planar chiral organonitrogen cycles, Journal of the American Chemical Society, 10.1021/ja1024657, 132, 27, 9232-9233, 2010.07, Enantioselective synthesis of a planar chiral organonitrogen cycle has been newly developed based on the unprecedented prochiral face-selective cyclization of achiral linear precursors by an appropriate chiral promoter..
65. Tomooka, K.; Uehara, K.; Nishikawa, R.; Suzuki, M.; Igawa, K., Enantioselective Synthesis of Planar Chiral Organonitrogen Cycles, J. Am. Chem. Soc., 132, 27, 9232-9233., 2010.06.
66. Igawa K.; Kokan N.; Tomooka K., Asymmetric Synthesis of Chiral Silacarboxylic Acids and Their Ester Derivatives, Angew. Chem. Int. Ed., 49, 4, 728-731., 2010.01.
67. Kazunobu Igawa, Naoto Kokan, Katsuhiko Tomooka, Asymmetrie synthesis of chiral silacarboxylic acids and their ester derivatives, Angewandte Chemie - International Edition, 10.1002/anie.200904922, 49, 4, 728-731, 2010.01, Sila analogues: The first asymmetric synthesis of silacarboxylic acids with a stereogenic center at the silicon atom has been achieved from chiral nonracemic silanols, without loss of optical purity. Silacarboxylic acids can be converted into their corresponding esters using a Mitsunobu-type reaction..
68. Uehara K.; Tomooka K., Planar Chiral Organosulfur Cycles, Chem. Lett., 38, 11, 1028-1029., 2009.10.
69. Kazuhiro Uehara, Katsuhiko Tomooka, Planar chiral organosulfur cycles, Chemistry Letters, 10.1246/cl.2009.1028, 38, 11, 1028-1029, 2009.10, Newly synthesized 9-membered diallylic organosulfur cycles have proven to possess planar chirality originating from the rigidity of their medium-sized cyclic structure. The oxidation state of the sulfur atom significantly influences their stereochemical behavior as well as their reactivity..
70. Igawa, K.; Takada, J.; Shimono, T.; Tomooka, K., Enantioselective Synthesis of Silanol, J. Am. Chem. Soc., 130, 48, 16132-16133., 2008.12.
71. Kazunobu Igawa, Junko Takada, Tomohiro Shimono, Katsuhiko Tomooka, Enantioselective synthesis of silanol, Journal of the American Chemical Society, 10.1021/ja805848z, 130, 48, 16132-16133, 2008.12, An enantioselective nucleophilic substitution reaction of achiral dialkoxysilane has been developed. The reaction proceeds with efficient stereocontrol on the silicon chirality center to give the enantioenriched silyl ether, which can be converted to the silanol without loss of enantiopurity. We have analyzed the steric course of the reaction by using DFT calculations and propose a transition state model to explain the observed enantioselectivity..
72. Katsuhiko Tomooka, Toshiyuki Akiyama, Phewluangdee Man, Masaki Suzuki, Asymmetric synthesis of (-)- and (+)-kainic acid using a planar chiral amide as a chiral building block, Tetrahedron Letters, 10.1016/j.tetlet.2008.08.058, 49, 44, 6327-6329, 2008.10, Both enantiomers of kainic acid have been synthesized from enantioenriched planar chiral cyclic amide 2a. The C3 and C4 stereocenters in the pyrrolidine ring were constructed by transannular Cope rearrangement of 2a, and the carboxyl group at the C2 position was introduced through lithiation followed by a carboxylation in the presence of an external chiral ligand..
73. Katsuhiko Tomooka, Masaki Suzuki, Kazuhiro Uehara, Maki Shimada, Toshiyuki Akiyama, Novel synthetic approach to nine-membered diallylic amides
Stereochemical behavior and utility as chiral building block, Synlett, 10.1055/s-2008-1078235, 16, 2518-2522, 2008.10, An efficient approach to nine-membered diallylic cyclic amides having a variety of substituents has been developed. The synthesized amides have stable planar chirality at ambient temperature. The transformation of the enantiomerically enriched amides provides optically active compounds containing stereogenic centers in a stereospecific fashion. As a demonstration of the synthetic utility of the amides, we have synthesized (+)-γ-lycorane using such an optically active amide as a chiral building block..
74. Tomooka, K.; Suzuki, M.; Uehara, K.; Shimada, M.; Akiyama, T., Novel Synthetic Approach to Nine-Membered Diallylic Amides: Stereochemical Behavior and Utility as Chiral Building Block, Synlett, 16, 2518-2522., 2008.09.
75. Tomooka, K.; Akiyama, T.; Man, P.; Suzuki, M., Asymmetric Synthesis of (-)- and (+)-Kainic acid using a Planar Chiral Amide as a Chiral Building Block, Tetrahedron Letters, 49, 6327-6329., 2008.09.
76. Nakazaki, A.; Usuki, J.; Tomooka, K., Stereoselective 1,4-Phenyl Migration from Silicon to Carbon in α-Siloxy Cyclic Acetal Systems: A Concise Synthesis of 1,2-cis-Phenyl C-Glycoside and Enantioenriched Silanol, Synlett, 13号,2064-2068頁, 2008.07.
77. Igawa, K.; Sakita, K.; Murakami, M.; Tomooka, K., Partial Oxydation of Alkenylsilane with Ozone: A Novel Stereoselective Approach for the Diol- and Triol-derivatives, Synthesis, 10号,1641-1645頁, 2008.05.
78. Tomooka, K.; Sakamaki, J.; Harada, M.; Wada, R., Enantioselective [1,2]-Stevens rearrangement using sugar-derived alkoxides as chiral promoters, Synlett, 5号,683-686頁, 2008.03.
79. Takeuchi, D.; Yasuda, A.; Okada, T.; Kuwabara, J.; Osakada, K.; Tomooka, K., Copolymerization of 7-Methylenebicyclo[4.1.0]heptane with Carbon Monooxide Initiated by Optically Active Palladium Complexes, Helv. Chim. Acta, 89巻,1574-1588頁, 2006.08.
80. Tomooka, K.; Tomoyasu, T.; Hanji, T.; Igawa, K., Anionic Ring-Enlarging Reaction of a Hemiaminal System: Stereoselective Approach to Disubstituted Tetrahydroisoquinolone, Synlett, 15号,2449-2453頁, 2006.08.
81. Murakami, M.; Sakita, K.; Igawa, K.; Tomooka, K., Stereoselective Oxy-Functionalization of γ-Silyl Allylic Alcohols with Ozone: A Facile Synthesis of Silyl Peroxide and Its Reactions, Organic Letters, 8巻,18号,4023-4026頁, 2006.08.
82. Nakazaki, A.; Nakai, T.; Tomooka, K., Asymmetric Retro-[1,4] Brook Rearrangement and its Stereochemical Course at Silicon, Angew. Chem. Int. Ed., 45巻,14号,2235-2238頁, 2006.03.
83. Tomooka, K.; Suzuki, M.; Shimada, M.; Yanagitsuru, S.-i.; Uehara, K., Planar Chiral Cyclic Amine and Its Derivatives: Synthesis and Stereochemical Behavior, Organic Letters, 8巻,5号,2449-2453頁, 2006.01.
84. Igawa K.; Tomooka, K., γ-Silyl Group Effect in Hydroalumination and Carbolithiation of Propargylic Alcohols, Angew. Chem. Int. Ed., 45巻,2号,232-234頁, 2005.12.
85. Tomooka, K.; Komine, N.; Fujiki, D.; Nakai, T.; Yanagitsuru, S., Planar Chiral Cyclic Ether: Asymmetric Resolution and Chirality Transformation, J. Am. Chem. Soc., 127巻,35号,12182-12183頁, 2005.08.
86. Tomoyasu,T.;Tomooka,K., Aza-Wittig Rearrangement of N,N-Dipropargylic α-Amino Alkyllithiums and Periselectivitiy and Steric Course, Synlett, 11号,1925-1928頁, 2004.09.
87. Suzuki,M.;Tomooka,K., Anionic Ring-Contraction Reaction of Cyclic Acetal System: Stereoselective Approach to Multi-Functionalized Oxetanes, Synlett, 4号,651-654頁, 2004.03.
88. Harada, M.; Nakai, T.; Tomooka, K., Stevens Rearrangement of a Cyclic HemiacetalSystem: Diastereoselective Approach to Chiral α-Amino Ketone., Synlett, 2号,365−367頁, 2004.02.
89. Tomoyasu, T.; Tomooka, K.; Nakai, T., Asymmetric synthesis of enantio-enriched acyclic α-amino alkylstannanes and rearrangement behaviour of carbanions thereof, Tetrahedron Lett., 44巻,6号,1239-1242頁, 2003.02.
90. Tomooka, K.; Harada, M.; Hanji, T.; Nakai, T., Ortho-[2,3]-Wittig Rearrangement of Benzyl Propargyl Ethers: Striking Preference over the Competing [1,2]-Wittig Rearrangement, Chem. Lett., 12号,1394-1395頁, 2000.12.
91. Tomooka, K.; Yamamoto, H.; Nakai, T., Stereoselective Synthesis of Highly Functionalized C-Glycosides based on the Acetal [1,2]- and [1,4]-Wittig Rearrangements, Angew. Chem. Int. Ed., 39巻,24号,4500-4502頁, 2000.12.
92. Tomooka, K.; Kikuchi, M.; Igawa, K.; Suzuki, M.; Keong, P.-h.; Nakai, T., Stereoselective Total Synthesis of Zaragozic Acid A based on an Acetal [1,2]-Wittig Rearrangement, Angew. Chem. Int. Ed., 39巻,24号,4503-4505頁, 2000.12.
93. Tomooka, K.; Komine, N.; Nakai, T., External Chiral Ligand-induced Enantioselective Versions of The [2,3]-Wittig Sigmatropic Rearrangement, Chirality, 12巻,5-6号,505-509頁, 2000.05.
94. Tomooka, K.; Inoue, T.; Nakai, T., Stereochemistry and Mechanism of Vinyl-migrating [1,2]-Wittig Rearrangement of

α-Lithioalkyl Vinyl Ether, Chem. Lett., 29巻,4号,418-419頁, 2000.04.
95. Komine, N.; Tomooka, K.; Nakai, T., Modified Cyclization of Enantio-enriched α-Homoallyloxy- Alkyllithiums Generated by

Sn-Li Transmetallation: Effects of Additives and Structural Requirement, Heterocycles, 52巻,3号,1071-1074頁, 2000.03.
96. Tomooka, K.; Wang, L.-F.; Okazaki, F.; Nakai, T., External Chiral Ligand-induced Enantioselective Lithiation / SE2 Reactions of

Isochroman and Phthalan, Tetrahedron Lett., 41巻,32号,6121-6125頁, 2000.02.
97. Tomoyasu, T.; Tomooka, K.; Nakai, T., Generation and Asymmetric Michael Addition Reaction of Chirally N-Protected

α-Aminoalkyl Cyanocuprates, Tetrahedron Lett., 41巻,3号,345-349頁, 2000.01.
98. Tomooka, K.; Nakazaki, A.; Nakai, T., A Novel Aryl Migration from Silicon to Carbon: An Efficient Approach to Asymmetric Synthesis of α-Aryl β-Hydroxy Cyclic Amines and Silanols, J. Am. Chem. Soc., 122巻,2号,40-409頁, 2000.01.
99. Tomooka, K.; Yamamoto, K.; Nakai, T., Enantioselective [1,2]-Wittig Rearrangement using an External Chiral Ligand, Angew. Chem. Int. Ed., 38巻,24号,3741-3743頁, 1999.12.
100. Komine, N.; Wang, L. F.; Tomooka, K.; Nakai, T., Enantioselective Carboxylation of α-Methoxybenzyllithium generated via Asymmetric Lithiation with a t-BuLi / chiral bis(oxazoline) Complex, Tetrahedron Lett., 40巻,37号,6809-6812頁, 1999.09.
101. Tomooka, K.; Wang, L. F.; Komine, N.; Nakai, T., Enantioselective Reactions of α-Methoxybenzyllithium generated by t-BuLi/ chiral bis(oxazoline) Complex with Aldehydes, Tetrahedron Lett., 40巻,37号,6813-6816頁, 1999.09.
102. Tomooka, K.; Shimizu, H.; Inoue, T.; Shibata, H.; Nakai, T., 1,2-Carbamoyl Migration on Enantio-enriched α-Lithioalkyl Carbamates generated with s-Butyllithium / Sparteine: Steric Course and Mechanism, Chem. Lett., 8号,759-760頁, 1999.08.
103. Tomooka, K.; Kikuchi, M.; Igawa, K.; Keong, P.-H.; Nakai, T., Stereochemical Features of the [1,2]-Wittig Rearrangement of O-Glycosides derived from D-Galactono- and D-Xylono-γ-Lactones: A New Approach to the Core Part of Zaragozic Acids, Tetrahedron Lett., 40巻,10号,1917-1920頁, 1999.03.
104. Tomoyasu, T.; Tomooka, K.; Nakai, T., A New Approach to Asymmetric Synthesis of β-Amino Alcohols by means of α-Chirally Protected Amino Alkyllithiums, Synlett, 10号,1147-1149頁, 1998.10.
105. Tomooka, K.; Takeda, T.; Kuen, A.-W.; Nakai, T., A New Synthetic Approach to A Fungal β-Lactone based on The Asymmetric [2,3]-Wittig Rearrangement, Heterocycles, 47巻,2号,671-674頁, 1998.08.
106. Qian, C,-P.; Liu, Y.-Z.; Tomooka, K.; Nakai, T., Generation and Use of Lithium Pentafluoropropen-2-Olate: 4-Hydroxy-1,1,1,3,3-Pentafluoro-2-Hexanone Hydrate, Organic Synthese, 76巻, 151-158頁, 1998.01.
107. Tomooka, K.; Komine, N.; Nakai, T., Enantioselective [2,3]-Wittig Rearrangement induced by Asymmetric Lithiation with a t-Butyllithium / Chiral Bis(oxazoline) System, Tetrahedron Lett., 39巻,#号,5513-5516頁, 1998.01.
108. Tomooka, K.; Komine, N.; Sasaki, T.; Shimizu, H.; Nakai, T., Enantioselective Carbanion Cyclization of 5-Alkenyl Carbamates induced by Asymmetric Lithiation with s-Butyllithium / (-)-Sparteine System, Tetrahedron Lett., 39巻,#号,9715-9718頁, 1998.01.