Kyushu University Academic Staff Educational and Research Activities Database
List of Papers
Kazunobu Igawa Last modified date:2020.09.25

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


Papers
1. Riki Iwai, Satoshi Suzuki, Shunsuke Sasaki, Amir Sharidan Sairi, Kazunobu Igawa, Tomoyoshi Suenobu, Keiji Morokuma, Gen ichi Konishi, Bridged Stilbenes
AIEgens Designed via a Simple Strategy to Control the Non-radiative Decay Pathway, Angewandte Chemie - International Edition, 10.1002/anie.202000943, 2020.01, To broaden the application of aggregation-induced emission (AIE) luminogens (AIEgens), the design of novel small-molecular dyes that exhibit high fluorescence quantum yield (Φfl) in the solid state is required. Considering that the mechanism of AIE can be rationalized based on steric avoidance of non-radiative decay pathways, a series of bridged stilbenes was designed, and their non-radiative decay pathways were investigated theoretically. Bridged stilbenes with short alkyl chains exhibited a strong fluorescence emission in solution and in the solid state, while bridged stilbenes with long alkyl chains exhibited AIE. Based on this theoretical prediction, we developed the bridged stilbenes BPST[7] and DPB[7], which demonstrate excellent AIE behavior..
2. 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..
3. 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..
4. Amir Sharidan Sairi, Kohei Kuwahara, Shunsuke Sasaki, Satoshi Suzuki, Kazunobu Igawa, Masatoshi Tokita, Shinji Ando, Keiji Morokuma, Tomoyoshi Suenobu, Gen Ichi Konishi, Synthesis of fluorescent polycarbonates with highly twisted
N, N -bis(dialkylamino)anthracene AIE luminogens in the main chain, RSC Advances, 10.1039/c9ra03701b, 9, 38, 21733-21740, 2019.01, A synthetic route to embed aggregation-induced-emission-(AIE)-active luminophores in polycarbonates (PCs) in various ratios is reported. The AIE-active monomer is based on the structure of 9,10-bis(piperidyl)anthracene. The obtained PCs display good film-forming properties, similar to those observed in poly(bisphenol A carbonate) (Ba-PC). The fluorescence quantum yield (Φ) of the PC with 5 mol% AIE-active monomer was 0.04 in solution and 0.53 in solid state. Moreover, this PC is also miscible with commercially available Ba-PC at any blending ratio. A combined analysis by scanning electron microscopy and differential scanning calorimetry did not indicate any clear phase separation. These results thus suggest that even engineering plastics like polycarbonates can be functionalized with AIE luminogens without adverse effects on their physical properties..
5. 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..
6. 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..
7. 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, 2019.01, 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..
8. 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..
9. Yuki Arakawa, Satoyoshi Inui, Kazunobu Igawa, Hideto Tsuji, Alkylthio- and alkyl-substituted asymmetric diphenyldiacetylene-based liquid crystals
phase transitions, mesophase and single-crystal structures, and birefringence, Liquid Crystals, 10.1080/02678292.2019.1590744, 46, 11, 1621-1630, 2019.09, Asymmetric diphenyldiacetylenes (DPDAs) bearing a fixed hexylthio group and different alkyl groups with carbon numbers (n) of 0–8 and 12 at each termini (or 4- and 4ʹ- positions), abbreviated as 6S–DPDA–n, were synthesised and their phase transition behaviour and birefringence were evaluated. It was found that alkyl-unsubstituted and methyl-substituted analogues (6S–DPDA–0 and 6S–DPDA–1, respectively) do not show any mesophases, whereas 6S–DPDA–n (n ≥ 2) form enantiotropic liquid crystal phases. Wherein, the nematic (N) phase for 6S–DPDA–4 is supercooled to room temperature, and 6S–DPDA–12 forms not only N phase but also highly ordered mesophase under room temperature. In light of the fact that symmetrically alkylthio-possessing 6S–DPDA–S6, 6S–DPDA–0 and 6S–DPDA–1 are not mesogenic, the present results strongly suggest that an alkyl group opposite to an alkylthio group plays a vital role to induce mesophases. Single-crystal X-ray analysis revealed anti-parallel packed molecules in the lattice. 6S–DPDA–7 have higher birefringence than 7–DPDA–7 being the symmetric alkyl counterpart, over the entire range of each N phase, which is supported by the enhanced polarisabilities based on density functional theory calculation..
10. 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..
11. 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
5+
, which is connected through a fourfold rotaxane, was prepared. Heterodimer 3
5+
catalyzed ethane oxidation in the presence of H
2
O
2
at a relatively low temperature. The site-selective complexation of 3
5+
with an additional anionic porphyrin (TPPS
4−
) through π–π stacking and electrostatic interactions afforded a stable 1:1 complex. It was demonstrated that the supramolecular post-synthetic modification of 3
5+
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
4−
to 3
5+
enhanced the catalytic activity..
12. 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..
13. 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.
14. 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..
15. 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..
16. 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..
17. Kazunobu Igawa, Daisuke Yoshihiro, Yusuke Abe, and Katsuhiko Tomooka, Enantioselective Synthesis of Silacyclopentanes, Angewandte Chemie International Edition, 10.1002/anie.201511728, 55, 5814-5818, 2016.04, A variety of functionalized silacyclopentanes were synthesized stereoselectively by highly enantioselective β-elimination of silacyclopentene oxides, followed by stereospecific transformations. The reaction mechanism of the β-elimination was elucidated by DFT calculations. The in vitro biological assay of an oxy-functionalized silacyclopentane showed substantial binding activity to a serotonin receptor protein..
18. Megumi Okada, Ryuichi Nishiyori, Shiho Kaneko, Kazunobu Igawa, Seiji Shirakawa, KI–Tetraethylene Glycol Complex as an Effective Catalyst for the Synthesis of Cyclic Thiocarbonates from Epoxides and CS2, Europian Journal of Organic Chemistry , 10.1002/ejoc.201800284, 2018, 17, 2022-2027, 2018.05, An efficient synthesis of cyclic thiocarbonates from epoxides and CS2 under mild reaction conditions was achieved when a KI–tetraethylene glycol complex was used as a readily available and economic catalyst. The effects of various glycols and alkali metal halides were investigated in the present work to clarify the importance of both KI and tetraethylene glycol. The reaction mechanisms for the synthesis of cyclic thiocarbonates are discussed on the basis of the stereochemistry of the products..
19. 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..
20. 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, Europian 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..
21. 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..
22. 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..
23. 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..
24. Shunsuke Sasaki, Satoshi Suzuki, Kazunobu Igawa, Keiji Morokuma, Gen Ichi Konishi, The K-Region in Pyrenes as a Key Position to Activate Aggregation-Induced Emission
Effects of Introducing Highly Twisted N,N-Dimethylamines, Journal of Organic Chemistry, 10.1021/acs.joc.7b00996, 82, 13, 6865-6873, 2017.07, A new design strategy to activate aggregation-induced emission (AIE) in pyrene chromophores is reported. In a previous report, we demonstrated that highly twisted N,N-dialkylamines of anthracene and naphthalene induce drastic AIE when these donors are introduced at appropriate positions to stabilize the S1/S0 minimum energy conical intersection (MECI). In the present study, this design strategy was applied to pyrene: the introduction of N,N-dimethylamine substituents at the 4,5-positions of pyrene, the so-called K-region, are likely to stabilize MECIs. To examine this hypothesis, four novel pyrene derivatives, which contain highly twisted N,N-dimethylamino groups at the 4- (4-Py), 4,5- (4,5-Py), 1- (1-Py), or 1,6-positions (1,6-Py) were tested. The nonradiative transitions of 4,5-Py are highly efficient (knr = 57.1 × 107 s-1), so that its fluorescence quantum yield in acetonitrile decreases to φfl = 0.04. The solid-state fluorescence of 4,5-Py is efficient (φfl = 0.49). In contrast, 1,6-Py features strong fluorescence (φfl = 0.48) with a slow nonradiative transition (knr = 11.0 × 107 s-1) that is subject to severe quenching (φfl = 0.03) in the solid state. These results underline that the chemistry of the pyrene K-region is intriguing, both from a photophysical perspective and with respect to materials science..
25. Kazunobu Igawa, Shin Aoyama, Yuuya Kawasaki, Takeru Kashiwagi, Yuki Seto, Runyan Ni, Naoto Mitsuda, Katsuhiko Tomooka, Thieme Chemistry Journals Awardees
Where Are They Now? One-Pot Synthesis of Versatile Buckle Units for Click Chemistry: 4,8-Diazacyclononynes (DACNs), Synlett, 10.1055/s-0036-1588839, 2017.04, 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..
26. 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..
27. Kazunobu Igawa, Asymmetric synthesis of chiral silicon molecules and stereoselective transformations thereof, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 10.5059/yukigoseikyokaishi.75.898, 75, 9, 898-908, 2017.01, A variety of functionalized chiral silicon molecules were stereoselectively synthesized from enantio-enriched chiral silanols or chiral silacyclopentenols, which were prepared by highly enantioselective desymmetrization reactions of achiral silicon molecules. The unique reactivity, and substantial bioactivity of the synthesized chiral silicon molecules were disclosed..
28. 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..
29. 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, 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..
30. Yuki Arakawa, Yukito Sasaki, Kazunobu Igawa, Hideto Tsuji, Hydrogen bonding liquid crystalline benzoic acids with alkylthio groups
Phase transition behavior and insights into the cybotactic nematic phase, New Journal of Chemistry, 10.1039/c7nj00282c, 41, 14, 6514-6522, 2017, A simple but novel class of hydrogen bonding liquid crystalline benzoic acids with alkylthio (or alkylsulfanyl; SR) groups was established. In general, although it is difficult for laterally non-substituted rod-like molecules with an alkylthio group to form some mesophases, the present molecules exclusively form a nematic (N) regime, owing to spontaneous carboxylic dimerization. It was found that the number of carbons in the alkylthio groups strongly correlated with transition temperatures as well as nematogenic stability: odd-even effects. Even-members displayed wider monotropic and enantiotropic N phases, despite the fact that almost all odd-members showed either none or only monotropic-narrower ones. Interestingly, their thermal transition temperatures were lower compared to those for alkoxy (OR) analogues, on account of the small angle (or large bend) of the C-S-C bond as well as the low electron density on their aromatic ring due to the weak electron donor properties of alkylthio groups. Additionally, in-depth wide-angle X-ray diffraction measurements revealed that an alkylthio analogue exhibited significantly enhanced smectic clusters formed in the N regime (or Ncyb phase) as well as the cluster type close to smectic (Sm) A, in comparison with an alkoxy analogue exhibiting a clear SmC-type cluster. The results indicate that a robust S⋯S intermolecular interaction for an alkylthio group into a mesogen affects the kind of smectic cluster in the Ncyb phase..
31. 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, 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..
32. 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..
33. 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..
34. Hirofumi Yamamoto, Maho Ueda, Naoto Yamasaki, Akiyoshi Fujii, Ikuo Sasaki, Kazunobu Igawa, Yusuke Kasai, Hiroshi Imagawa, Mugio Nishizawa, Aryl-Allene Cyclization via a Hg(OTf)(2)-Catalytic Pathway, ORGANIC LETTERS, 10.1021/acs.orglett.6b01144, 18, 12, 2864-2867, 2016.06.
35. Shunsuke Sasaki, Satoshi Suzuki, W. M. C. Sameera, Kazunobu Igawa, Keiji Morokuma, Gen-ichi Konishi, Highly Twisted N,N‐Dialkylamines as a Design Strategy to Tune Simple Aromatic Hydrocarbons as Steric Environment-Sensitive Fluorophores, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 10.1021/jacs.6b03749, 138, 8194-8206, 2016.06.
36. 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, 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..
37. Suguru Yoshida, Takahisa Yano, Yasuyuki Sugimura, Kazunobu Igawa, Shigeomi Shimizu, Katsuhiko Tomooka, Takamitsu Hosoya, Direct Thioamination of Arynes via Reaction with Sulfilimines and Migratory N-Arylation, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 10.1021/jacs.5b10557, 137, 44, 14071-14074, 2015.11.
38. Kazunobu Igawa, Nobumasa Ichikawa, 阿野 勇介, Keisuke Katanoda, Toshiyuki Akiyama, Masato Ito, Katsuhiko Tomooka, Catalytic Enantioselective Synthesis of Planar-Chiral Cyclic Amides Based on a Pd-Catalyzed Asymmetric Allylic Substitution Reaction, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 10.1021/jacs.5b04340, 137, 23, 7294-7297, 2015.06.
39. Ryo Irie, Masaki Furusawa, Kosuke Arita, Kazunobu Igawa, Katsuhiko Tomooka, New synthetic approaches to fused polyheterocyclic compounds by using domino cyclization reactions of aromatic diyne and enyne systems, Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry, 72, 10, 1131-1142, 2014.10, Oxa-heterocyclic compounds such as benzofurans, chromenes, and chromanes constitute a diverse array of biologically active materials. Furthermore, extended π-conjugated systems, in which oxa-heteroaromalic and benzene rings are condensed alternately, have been exploited as components of photoelectronic devices. Thus, the development of efficient synthetic approaches toward these valuable classes of heterocycles has been pursued. Among those precedented hetero-cyclization methods, domino cyclodehydrogenation and cycloisomerization reactions are highly attractive as they could produce elaborate heterocyclic frameworks from readily available starting materials in an atom-efficient manner. Herein, we wish to report the novel multimode domino ring-forming reactions of o-phenylenediyne-linked bis(arenol)s (aromatic diyne systems) and its analogous aromatic enyne systems to provide unique fused oxa-heterocycles, which are otherwise difficult to synthesize..
40. Katsuhiko Tomooka, Shouji Miyasaka, Shogo Motomura, Kazunobu Igawa, 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.
41. Kazunobu Igawa, Yuuya Kawasaki, Kosuke Nishino, Naoto Mitsuda, Katsuhiko Tomooka, Asymmetric Ozone Oxidation of Silylalkene Using a C2-Symmetrical Dialkoxysilyl Group as a Chiral Auxiliary, Chem. Eur. J., 10.1002/chem.201402996, 20, 9255-9258, 2014.05.
42. Fumi Takahashi-Yanaga, Tatsuya Yoshihara, 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, 2014.02.
43. 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 Letters, 10.1016/j.tetlet.2013.10.080, 54, 52, 7107-7110, 2013.12, We describe the transition metal-free base-catalyzed Schmittel cycloisomerization reactions of o-phenylene-linked bis(arenol)s to indeno[1,2-c]chromene derivatives through prototropic rearrangement (tautomerization) to a putative vinylidene o-quinone methide intermediate with an enyne-allene system followed by a formal inverse-electron-demand hetero Diels-Alder cycloaddition. The preliminary results on catalytic asymmetric cycloisomerization with chiral bases are also disclosed..
44. 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., 10.1246/cl.130411, 54, 7107-7110, 2013.10.
45. Kazunobu Igawa, Runyan Ni, Takeshi Kawabata, Katsuhiko Tomooka, Synthesis, Structural Analysis, and Reaction of 3-Aza-5-[7]orthocyclophyne, Chem. Lett., 10.1246/cl.130735, 42, 1374-1376, 2013.10.
46. Takashi Kamachi, Ken-ichi Shimizu, Daisuke Yoshihiro, 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.
47. 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.
48. Takeshi Tsuji, Tatsuya Yahata, Masato Yasutomo, Kazunobu Igawa, Masaharu Tsuji, Yoshie Ishikawa, Naoto Koshizaki, Preparation and Investigation of the Formation Mechanism of Submicron-sized Spherical Particles of Gold using Laser Ablation and Laser Irradiation in Liquids, Phys. Chem. Chem. Phys., 10.1039/c2cp44159d, 15, 3099-3107, 2013.01.
49. 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, 今回,我々はアリールスルホンアミドに対してホスフィドアニオンを作用させると,窒素上での求核置換反応が進行することを見出した.本反応は,窒素上の変換反応として,また,アリールスルホンアミド保護の効率的な除去法として有用である..
50. 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, 今回,我々はキラルケイ素分子の効率的な不斉合成法としてジヒドロシランの不斉非対称化を伴うアルキンとのヒドロシリル化反応を新たに開発することに成功した..
51. 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.
52. Keisuke Kojima, Katsumi Chikama, Makoto Ishikawa, Akihiro Tanaka, Takashi Nishikata, 堤 大典, Hideo Nagashima, Kazunobu Igawa, Hydrophobicity/Hydrophilicity Tunable Hyperbranched Polystyrenes as Novel Supports for Transition-metal Nanoparticles, Chemical Communcation, 10.1039/c2cc35390c, 48, 10666-10668, 2012.09.
53. Ryo Irie, Akihiro Tanoue, Suguru Urakawa, Tatsushi Imahori, Kazunobu Igawa, Taisuke Matsumoto, Katsuhiko Tomooka, Shinsuke Kikuta, Tatsuya Uchida, Tsutomu Katsuki, Synthesis and Stereochemical Behavior of a New Chiral Furano[7]helicene, Chem. Lett., 40, 1343-1345, 2011.12.
54. Yuuya Kawasaki, Youhei Ishikawa, Kazunobu Igawa, Katsuhiko Tomooka, Directing Group-Controlled Hydrosilylation: Regioselective Functionalization of Alkyne, J. Am. Chem. Soc., 133, 20712-20715, 2011.12, アルキンのヒドロシリル化は合成化学的に有用なアルケニルシランの合成法として優れているが,その位置選択が低いことから適用範囲が限られていた.これに対して,本研究ではアルキンの近傍にジメチルビニルシリル基を配向基として配するという新手法を開発し,ヒドロシリル化の位置選択性の高度制御に成功した..
55. Katsuhiko Tomooka, Hiroko Inoue, Kazunobu Igawa, Synthesis and Stereochemical Behavior of (E)-Cyclononene Derivatives, Chem. Lett., 10.1246/cl.2011.591, 40, 591-593, 2011.06.
56. 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 DCM mouse model, J. Pharm. Exp. Therap., 338, 1, 2-11, 2011.05.
57. Kazunobu Igawa, Yuuya Kawasaki, and Katsuhiko Tomooka, Addition-type Oxidation of Silylalkene Using Ozone: An Efficient Approach for Acyloin and Its Derivatives, Chem. Lett., 40, 233-235, 2011.02.
58. Katsuhiko Tomooka, Takayuki Ezawa, Hiroko Inoue, Kazuhiro Uehara, Kazunobu Igawa, Dynamic Chirality of (E)-5-Cyclononen-1-one and its Enolate, J. Am. Chem. Soc., 133, 1754-1756, 2011.01.
59. 井上 寛子,井川 和宣,友岡 克彦, trans-シクロノネン骨格を有するケトエステル誘導体の合成とその立体化学的挙動, 九州大学大学院総合理工学報告, 32, 19-22, 2010.11.
60. Katsuhiko Tomooka, Kazuhiro Uehara, Rie Nishikawa, Masaki Suzuki, Kazunobu Igawa, Enantioselective Synthesis of Planar Chiral Organonitrogen Cycles, J. Am. Chem. Soc, 132, 9232-9233, 2010.06.
61. Kazunobu Igawa, Naoto Kokan, and Katsuhiko Tomooka, Asymmetric Synthesis of Chiral Silacarboxylic Acids and Their Ester Derivatives, Angew. Chem. Int. Ed., 49, 728-731, 2010.01.
62. Igawa, K.; Takada, J.; Shimono, T.; Tomooka, K., Enantioselective Synthesis of Silanol, J. Am. Chem. Soc., 130, 16132-16133, 2008.12.
63. Yong-Li Zhong, Brenda Pipik, Jaemoon Lee, Yoshinori Kohmura, Shigemitsu Okada, Kazunobu Igawa, Chie Kadowaki, Akihiro Takezawa, Shinji Kato, David A. Conlon, Hua Zhou, Anthony O. King, Robert A. Reamer, Donald R. Gauthier, Jr., and David Askin, Practical Synthesis of a HIV Integrase Inhibitor, Orag. Proc. Res. Dev., 12, 1245-1252, 2008.08.
64. Kazunobu Igawa, Kyohei Sakita, Masanori Murakami, Katsuhiko Tomooka, Partial Oxydation of Alkenylsilane with Ozone: A Novel Stereoselective Approach for the Diol- and Triol-derivatives, Synthesis, 1641, 2008.02.
65. K. Tomooka, T. Tomoyasu, T. Hanji, K. Igawa, Anionic Ring-Enlarging Reaction of Hemiaminal System: Stereoselective Approach to Disubstituted Tetrahydroisoquinolone, Synlett, 2449-2453, 2006.09.
66. M. Murakami, K. Sakita, K. Igawa, K. Tomooka, Stereoselective Oxy-functionalization of γ-Silyl Allylic Alcohols with Ozone: A Facile Synthesis of Silyl Peroxide and Its Reactions, Organic. Lett., 8, 4023-4026, 2006.08.
67. K. Igawa, K. Tomooka, 3. γ-Silyl Group Effect in Hydroalumination and Carbolithiation of Propargylic Alcohols, Angew. Chem. Int. Ed., 45, 232-234, 2006.01.
68. K. Tomooka, M. Kikuchi, K. Igawa, M. Suzuki, P.-H. Keong and T. Nakai, Stereoselective Total Synthesis of Zaragozic Acid A based on an Acetal [1,2]-Wittig Rearrangement, Angew. Chem. Int. Ed., 39, 4502-4505, 2000.12.
69. K. Tomooka, M. Kikuchi, K. Igawa, P.-H. Keong and T. Nakai, 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, 1917-1920, 1999.03.
70. TakahiroKawatsu, HirokiTokushima, YuyaTakedomi, TatsushiImahori, 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.
71. Kazunobu Igawa, Daisuke Yoshihiro, Yusuke Abe, Katsuhiko Tomooka, Enantioselective Synthesis of Silacyclopentanes, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 10.1002/anie.201511728, 55, 19, 5814-5818.