Synthesis of Eight Stereoisomers of Pochonicine: Nanomolar Inhibition of beta-N-Acetylhexosaminidases
文献类型：期刊论文
| 作者 | Zhu, Jian-She1,6; Nakagawa, Shinpei3; Chen, Wei2; Adachi, Isao3; Jia, Yue-Mei1; Hu, Xiang-Guo1; Fleet, George W. J.4; Wilson, Francis X.5; Nitoda, Teruhiko7; Horne, Graeme5 |
| 刊名 | JOURNAL OF ORGANIC CHEMISTRY
 |
| 出版日期 | 2013-10-18 |
| 卷号 | 78期号:20页码:10298-10309 |
| ISSN号 | 0022-3263 |
| DOI | 10.1021/jo401694e |
| 英文摘要 | Pochonicine, the first naturally occurring polyhydroxylated pyrrolizidine containing an acetamidomethyl group, which was isolated from Pochonia suchlasporia var. suchlasporia TA/V1A 87, together with its enantiomer and their C-1 and/or C-3 epimers, have been synthesized from the sugar-derived cyclic nitrones 9D and 9L, respectively. An in-depth NMR study showed that both the H-1 and C-13 NMR spectra of the synthetic pochonicines (1D and 1L) matched very well with those of natural pochonicine in D2O, which unequivocally determined the relative configuration of the natural product as 1D or 1L. In addition, comparison of the optical rotations of the synthetic pochonicines and that of the natural product, but more convincingly their glycosidase inhibition profiles, confirmed the absolute configuration of natural pochonicine as 1R,3S,5R,6R,7S,7aR. Thereby, the structure of natural pochonicine was unequivocally determined as (+)-(1R,3S,5R,6R,7S,7aR)-pochonicine (113). Glycosidase inhibition experiments showed that natural pochonicine ID and its epimers 2D, 3D, and 4D all are powerful inhibitors of hexosaminidases (five beta-N-acetylglucosaminidases and two beta-N-acetylgalactosaminidases) while their enantiomers 1L, 2L, 3L, and 4L are much weaker inhibitors of the same enzymes. (-)-3-epi-Pochonicine (2L) was found to be a potent and selective inhibitor of a-L-rhamnosidase. None of the compounds showed any inhibition of alpha-GaINAcase. |
| 语种 | 英语 |
| WOS记录号 | WOS:000326122200025 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/42217]  |
| 专题 | 中国科学院化学研究所 |
| 通讯作者 | Kato, Atsushi |
| 作者单位 | 1.Chinese Acad Sci, BNLMS, CAS Key Lab Mol Recognit & Funct, Inst Chem, Beijing 100190, Peoples R China 2.Jiang Xi Normal Univ, Coll Chem & Chem Engn, Nanchang 330022, Jiangxi, Peoples R China 3.Toyama Univ, Dept Hosp Pharm, Toyama 9300194, Japan 4.Univ Oxford, Dept Chem, Chem Res Lab, Oxford OX1 3TA, England 5.Summit PLC, Abingdon OX14 4RY, Oxon, England 6.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 7.Okayama Univ, Grad Sch Environm & Life, Lab Bioresources Chem, Kita Ku, Okayama 7008530, Japan |
| 推荐引用方式 GB/T 7714 | Zhu, Jian-She,Nakagawa, Shinpei,Chen, Wei,et al. Synthesis of Eight Stereoisomers of Pochonicine: Nanomolar Inhibition of beta-N-Acetylhexosaminidases[J]. JOURNAL OF ORGANIC CHEMISTRY,2013,78(20):10298-10309. |
| APA | Zhu, Jian-She.,Nakagawa, Shinpei.,Chen, Wei.,Adachi, Isao.,Jia, Yue-Mei.,...&Yu, Chu-Yi.(2013).Synthesis of Eight Stereoisomers of Pochonicine: Nanomolar Inhibition of beta-N-Acetylhexosaminidases.JOURNAL OF ORGANIC CHEMISTRY,78(20),10298-10309. |
| MLA | Zhu, Jian-She,et al."Synthesis of Eight Stereoisomers of Pochonicine: Nanomolar Inhibition of beta-N-Acetylhexosaminidases".JOURNAL OF ORGANIC CHEMISTRY 78.20(2013):10298-10309. |
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来源：化学研究所
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