Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library

被引：81

作者：

Tsou, En-Lun ^{[1
]}

Chen, Sih-Yu ^{[1
]}

Yang, Ming-Hsun ^{[1
]}

Wang, Shih-Chi ^{[1
]}

Cheng, Ting-Ren Rachel ^{[1
]}

Cheng, Wei-Chieh ^{[1
]}

机构：

[1] Acad Sinica, Genom Res Ctr, Taipei 11529, Taiwan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 24期

关键词：

Polyhydroxylated pyrrolidine alkaloid; Natural product-like molecule; Chiral cyclic nitrone; Glycosidase inhibitors; Structural diversity;

D O I：

10.1016/j.bmc.2008.10.063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Inspired by polyhydroxylated pyrrolidine alkaloid natural products, a 18-membered library of 2-aryl polyhydroxylated pyrrolidines has been efficiently prepared in two or three synthetic steps from the known chiral cyclic nitrones with high yield and purity and excellent stereoselectivity. The inhibitory activity of all these compounds against various glycosidase enzymes was evaluated. Interestingly, 15 and 19 show better inhibitory activities than radicamine A ( 20) and B ( 18) against alpha-glucosidases. The IC50 values of 15 and 19 are 1.1 and 0.5 mu M, respectively. In this study, we also discovered the substituent(s) on the aryl ring could affect the inhibition potency and selectivity against glycosidases. (C) 2008 Elsevier Ltd. All rights reserved.

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页码：10198 / 10204

页数：7

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