Issue 42, 2016, Issue in Progress

Synthesis of hupehenols A, B, and E from protopanaxadiol

Abstract

Hupehenols A–E (3–7) are bioactive octanordammarane triterpenoids, among which hupehenols B (4) and E (7) are the most potent and selective human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors (IC50 = 15 and 34 nM, respectively). Herein, the hupehenols were synthesized from protopanaxadiol, the main component of Panax notoginseng. The different synthetic attempts resulted in the stereoselective synthesis of hupehenols A, B, and E for further biological exploration. Notable features of the synthesis included a regioselective epoxide-opening reaction, regioselective acetylation, and a late-stage stereoselective oxa-Michael addition. Semi-synthetic derivatization of these natural products led to the determination of their absolute configurations, a better understanding of their inherent reactivity patterns, and the required C-17 configuration for murine 11β-HSD1 inhibition. These studies provide the basis for the synthesis of 11β-HSD1 inhibitors as potential targets for the treatment of type 2 diabetes.

Graphical abstract: Synthesis of hupehenols A, B, and E from protopanaxadiol

Supplementary files

Article information

Article type
Paper
Submitted
16 Feb 2016
Accepted
01 Apr 2016
First published
04 Apr 2016

RSC Adv., 2016,6, 35792-35803

Synthesis of hupehenols A, B, and E from protopanaxadiol

L. Shao, J. Xu, X. Li, Z. Zhang, X. Shi, J. Ren, J. He, Y. Zhao, Y. Leng, C. Xia and Q. Zhao, RSC Adv., 2016, 6, 35792 DOI: 10.1039/C6RA04236H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements