| 1. |
Takahiro Ikazaki, Eri Ishikawa, Hiroto Tamashima, Hisako Akiyama, Yusuke Kimuro, Makoto Yoritate, Hiroaki Matoba, Akihiro Imamura, Hideharu Ishida, Sho Yamasaki, Go Hirai, Ligand-controlled Stereoselective Synthesis and Biological Activities of 2-Exomethylene Pseudo-glycoconjugates: Discovery of Mincle-Selective Ligands., Angewandte Chemie (International ed. in English), 10.1002/anie.202302569, 62, 22, e202302569, 2023.04, Glycoconjugate analogues in which the sp3-hybridized C2 position of the carbohydrate structure (normally bearing a hydroxyl group) is converted to a compact sp2-hybridized exo-methylene group are expected to have unique biological activities. We established ligand-controlled Tsuji-Trost-type glycosylation methodology to directly prepare a variety of these 2-exo-methylene pseudo-glycoconjugates, including glucosylceramide analogues, in an α- or β-selective manner. Glucocerebrosidase GBA1 cleaves these synthetic pseudo-β-glucosylceramides similarly to native glucosylceramides. The pseudo-glucosylceramides exhibit selective ligand activity towards macrophage-inducible C-type lectin (Mincle), but unlike native glucosylceramides, are inactive towards CD1d..  |
| 2. |
Daiki Takeda, Makoto Yoritate, Hiroki Yasutomi, Suzuka Chiba, Takahiro Moriyama, Atsushi Yokoo, Kazuteru Usui, Go Hirai, β-Glycosyl Trifluoroborates as Precursors for Direct α-C-Glycosylation: Synthesis of 2-Deoxy-α-C-glycosides, Organic Letters, 10.1021/acs.orglett.1c00402, 2021.03. |
| 3. |
Go Hirai, Marie Kato, Hiroyuki Koshino, Eri Nishizawa, Kana Oonuma, Eisuke Ota, Toru Watanabe, Daisuke Hashizume, Yuki Tamura, Mitsuaki Okada, Taeko Miyagi, Mikiko Sodeoka, Ganglioside GM3 Analogues Containing Monofluoromethylene-Linked Sialoside: Synthesis, Stereochemical Effects, Conformational Behavior, and Biological Activities, JACS Au, 10.1021/jacsau.0c00058, 2021.02, Glycoconjugates are an important class of biomolecules that regulate numerous biological events in cells. However, these complex, medium-size molecules are metabolically unstable, which hampers detailed investigations of their functions as well as their potential application as pharmaceuticals. Here we report sialidase-resistant analogues of ganglioside GM3 containing a monofluoromethylene linkage instead of the native O-sialoside linkage. Stereoselective synthesis of CHF-linked disaccharides and kinetically controlled Au(I)-catalyzed glycosylation efficiently furnished both stereoisomers of CHF-linked as well as CF2- and CH2-linked GM3 analogues. Like native GM3, the C-linked GM3 analogues inhibited the autophosphorylation of epidermal growth factor (EGF) receptor induced by EGF in vitro. Assay of the proliferation-enhancing activity toward Had-1 cells together with NMR-based conformational analysis showed that the (S)-CHF-linked GM3 analogue with exo-gauche conformation is the most potent of the synthesized compounds. Our findings suggest that exo-anomeric conformation is important for the biological functions of GM3.. |
| 4. |
Yu Hidaka, Noriaki Kiya, Makoto Yoritate, Kazuteru Usui, Go Hirai, Synthesis of CH2-linked alpha-galactosylceramide and its glucose analogues through glycosyl radical-mediated direct C-glycosylation, Chemical Communications, 10.1039/d0cc00785d, 56, 34, 4712-4715, 2020.04, We describe a new synthetic approach for C-linked glycolipid analogues, in which the cleavable O-glycosidic linkage is replaced by a carbon unit. Direct C-glycosylation of a conformationally constrained and stable C1-sp3 hybridized xanthate carbohydrate with carefully designed sphingosine units afforded the CH2-linked analogue of antitumor-active KRN7000 and its glucose congener.. |
| 5. |
Yusaku Nomura, Frédéric Thuaud, Daisuke Sekine, Akihiro Ito, Satoko Maeda, Hiroyuki Koshino, Daisuke Hashizume, Atsuya Muranaka, Thomas Cruchter, Masanobu Uchiyama, Satoshi Ichikawa, Akira Matsuda, Minoru Yoshida, Go Hirai, Mikiko Sodeoka, Synthesis of All Stereoisomers of Monomeric Spectomycin A1/A2 and Evaluation of Their Protein SUMOylation-Inhibitory Activity, Chemistry - A European Journal, 10.1002/chem.201901093, 25, 35, 8387-8392, 2019.06, A synthetic methodology to access all possible stereoisomers of spectomycin A1 (SMA1) and A2 (SMA2) has been established through late-stage diversification. The key reaction for the construction of all four diastereomers is an intramolecular cyclization based on the umpolung of π-allyl palladium species with bis(pinacolato)diborane (B2(pin)2). Silyl group assisted direct benzylic oxidation of each isomer enabled construction of the fragile β-hydroxytetralone skeleton to provide the SMAs. The relative and absolute stereochemistry of SMA2 was also determined, and the absolute stereochemistry of SMA1 was extrapolated based on the optical rotation of SMA2. The axial chirality of SMAs is discussed based on circular dichroism spectra and DFT calculations, and it is concluded that the M isomer is predominant in solution. Biochemical assessment of all isomers in vitro revealed that the C9 hydroxyl group and dimeric structure were both important for protein SUMOylation-inhibitory activity.. |
| 6. |
Yu Mikame, Kazuko Yoshida, Daisuke Hashizume, Go Hirai, Kazuo Nagasawa, Hiroyuki Osada, Mikiko Sodeoka, Synthesis of All Stereoisomers of RK460 and Evaluation of Their Activity and Selectivity as Abscisic Acid Receptor Antagonists, Chemistry - A European Journal, 10.1002/chem.201806056, 25, 14, 3496-3500, 2019.03, The PYR/PYL/RCAR protein families have recently emerged as receptors of the phytohormone abscisic acid (ABA, 1), which regulates plant responses to environmental stress. These families have multiple members with different physiological actions, and so selective agonists or antagonists are needed both as tools to elucidate functional differences and as lead compounds for agrochemicals. We previously identified RK460 (rac-3 a) as a PYR1-selective antagonist, and showed that it possesses five stereocenters on a 6,5-cis-bicyclo skeleton. Here, we synthesized all the stereoisomers of RK460 and evaluated their activity towards a panel of receptors. Relative stereochemistry as well as absolute stereochemistry was important for selective action.. |
| 7. |
Noriaki Kiya, Yu Hidaka, Kazuteru Usui, Go Hirai, Synthesis of CH2-Linked α(1,6)-Disaccharide Analogues by α-Selective Radical Coupling C-Glycosylation, Organic Letters, 10.1021/acs.orglett.9b00133, 21, 6, 1588-1592, 2019.03, C-Linked carbohydrate structure, in which the cleavable O-glycosidic linkage is replaced by a carbon unit, is a useful tool for functional analyses of glycoconjugates. We describe a synthetic method for α-CH2-linked disaccharide structures, such as Glc(1,6)-Glc, by stereoselective radical-coupling C-glycosylation between a conformationally constrained and stable C1-sp3 hybridized xanthate donor and a carefully designed acceptor.. |
| 8. |
Eisuke Ota, Kazuteru Usui, Kana Oonuma, Hiroyuki Koshino, Shigeru Nishiyama, Go Hirai, Mikiko Sodeoka, Thienyl-Substituted α-Ketoamide
A Less Hydrophobic Reactive Group for Photo-Affinity Labeling, ACS Chemical Biology, 10.1021/acschembio.7b00988, 13, 4, 876-880, 2018.02, Photoaffinity labeling (PAL) is an important tool in chemical biology research, but application of α-ketoamides for PAL has been hampered by their photoinstability. Here, we show that 2-thienyl-substituted α-ketoamide is a superior photoreactive group for PAL. Studies with a series of synthetic mannose-conjugated α-ketoamides revealed that 2-thienyl substitution of α-ketoamide decreased the electrophilicity of the keto group and reduced the rate of photodegradation. Mannose-conjugated thienyl α-ketoamide showed greater concanavalin A labeling efficiency than other alkyl or phenyl-substituted α-ketoamides. In comparison with representative conventional photoreactive groups, 2-thienyl ketoamide showed reduced labeling of nontarget proteins, probably owing to its lower hydrophobicity.. |
| 9. |
Morita Masaki, Shuntaro Kojima, Megumi Ohkubo, Hiroyuki Koshino, Daisuke Hashizume, Go Hirai, Keiji Maruoka, Mikiko Sodeoka, Synthesis of the Right-Side Structure of Type B Physalins, ISRAEL JOURNAL OF CHEMISTRY, 10.1002/ijch.201600110, 57, 309-318, 2017.04. |
| 10. |
Qianqian Wang, Yuta Kuramoto, Yozo Okazaki, Eisuke Ota, Masaki Morita, Go Hirai, Kazuki Saito, Mikiko Sodeoka, Synthesis of polyunsaturated fatty acid-containing glucuronosyl-diacylglycerol through direct glycosylation, Tetrahedron Letters, 10.1016/j.tetlet.2017.06.034, 58, 30, 2915-2918, 2017.01, We describe a total synthesis of a polyunsaturated fatty acid (PUFA)-containing glucuronosyldiacylglycerol (GlcADG), which is a surrogate glycolipid whose synthesis is remarkably upregulated in plant membranes under phosphorus-depleted conditions. Glycosylation between the glucuronide donor bearing 3,4-dimethoxybenzyl (DMPM) protecting groups and di-acylglycerol acceptor proceeded smoothly in the presence of gold(I) catalyst to provide the protected α-isomer of GlcADG as the major product.. |
| 11. |
Xiaoying Sun, Go Hirai, Masashi Ueki, Hiroshi Hirota, Qianqian Wang, Yayoi Hongo, Takemichi Nakamura, Yuki Hitora, Hidekazu Takahashi, Mikiko Sodeoka, Hiroyuki Osada, Makiko Hamamoto, Minoru Yoshida, Yoko Yashiroda, Identification of novel secreted fatty acids that regulate nitrogen catabolite repression in fission yeast, Scientific Reports, 10.1038/srep20856, 6, 20856, 2016.02. |
| 12. |
Eisuke Ota, Yu Mikame, Go Hirai, Shigeru Nishiyama, Mikiko Sodeoka, Photochemical and Additive-Free Coupling Reaction of α-Cumyl α-Keto Esters via Intermolecular C–H Bond Activation, SYNLETT, 10.1055/s-0035-1561098, 27, 1128-1132, 2016.01. |
| 13. |
Eisuke Ota, Yu Mikame, Go Hirai, Hiroyuki Koshino, Shigeru Nishiyama, Mikiko Sodeoka, Photo-induced formation of cyclopropanols from α-ketoamides via γ-C-H bond activation, Tetrahedron Lett., 10.1016/j.tetlet.2015.09.038, 56, 5991-5994, 2015.09. |
| 14. |
Masaaki Ozawa, Masaki Morita, Go Hirai, Satoru Tamura, Masao Kawai, Ayako Tsuchiya, Kana Oonuma, Keiji Maruoka, and Mikiko Sodeoka, Contribution of Cage-Shaped Structure of Physalins to Their Mode of Action in Inhibition of NF-kB Action, ACS Med. Chem. Lett. , 10.1021/ml400144e, 4, 730-735, 2013.06. |
| 15. |
Ayako Tsuchiya, Miwako Asanuma, Go Hirai, Kana Oonuma, Muhammad Muddassar, Eri Nishizawa, Yusuke Koyama, Yuko Otani, Kam Y. J. Zhang, and Mikiko Sodeoka, CDC25A-inhibitory RE Derivatives Bind to Pocket Adjacent to the Catalytic Site, Mol. BioSyst., 10.1039/C3MB00003F, 9, 1026-1034, 2013.02. |
| 16. |
Masaki Morita, Go Hirai, Meguni Ohkubo Hiroyuki koshino, Daisuke Hashizume, Keiji Maruoka, and Mikiko Sodeoka, Kinetically Controlled One-Pot Formation of DEFGH-Rings of Type B Physalins through Domino-Type Transformations, Org, Lett., 14, 3434-3437, 2012.06. |
| 17. |
Ayako Tsuchiya, Go Hirai, Yusuke Koyama, Kana Oonuma, Yuko Otani, Hiroyuki Osada, and Mikiko Sodeoka, Dual-specificity Protein Phosphatase CDC25A/B Inhibitor Identified from a Focused Library with Non-electrophilic Enamine Core Structure, ACS Med. Chem. Lett. , 10.1021/ml2002778, 3, 264-298, 2012.02. |
| 18. |
Go Hirai, Ayako Tsuchiya, Yusuke Koyama, Yuko Otani, Kana Oonuma, Kosuke Dodo, Siro Simizu, Hiroyuki Osada, and Mikiko Sodeoka, Development of a Vaccinia H1-Related (VHR) Phosphatase Inhibitor with NonAcidic Phosphate-Mimicking Core Structure, ChemMedChem, 10.1002/cmdc.201100107, 6, 617-622, 2011.03. |
| 19. |
Megumi Ohkubo, Go Hirai, Mikiko Sodeoka, Synthesis of the DFGH ring system of Type B Physalins: Highly Oxygenated, Cage-Shaped Molecules, Angew. Chem. Int. Ed., 10.1002/anie.200900634, 48, 3862-3866, 2009.04. |
| 20. |
Isao Fukuda, Akihiro Ito, Go Hirai, Shinichi Nishimura, Hisashi Kawasaki, Hisato Saitoh, Ken-ichi Kimura, Mikiko Sodeoka, Minoru Yoshida, Ginkgolic Acid Inhibits Protein SUMOylation by Blocking Formation of the E1-SUMO Intermediate, Chemistry & Biology, 10.1016/j.chembiol.2009.01.009, 16, 133-140, 2009.02. |
| 21. |
Toru Watanabe, Go Hirai, Marie Kato, Daisuke Hashizume, Taeko Miyagi, and Mikiko Sodeoka, Synthesis of CH2-Linked α(2,3)Sialylgalactose Analogue: On the Stereoselectivity of the Key Ireland-Claisen Rearrangement, Org. Lett., 10.1021/ol801519j, 10, 4167-4170, 2008.09. |
| 22. |
Go Hirai, Toru Watanabe, Kazunori Yamaguchi, Taeko Miyagi, and Mikiko Sodeoka, Stereocontrolled and Convergent Entry to CF2-Sialosides: Synthesis of CF2-Linked Ganglioside GM4, J. Am. Chem. Soc., 10.1021/ja075738w, 129, 15420-15421, 2007.11. |
