Issue 9, 2002

Parallel synthesis of new phenylalanino-2-(phenylthio)pyrrolidin-3-one scaffold-based analogues

Abstract

Based on the specific PhePro proteolytic cleavage of the HIV-protease, we synthesized short pseudopeptides incorporating a 2-(phenylthio)pyrrolidin-3-one ring. We previously described various analogues based on this scaffold. We report herein a parallel methodology with improved efficiency applied to the synthesis of new derivatives. For this purpose, we selected an intermediate, i.e.8, which can be used as a versatile synthon after simple removal of the N-Boc protecting group of the starting material as the penultimate reaction step. This new route improved the synthesis of these molecules in terms of numbers of reaction and in terms of both reagent and reaction time, and allowed the preparation of a small library focused on the phenylalanino-2-(phenylthio)pyrrolidin-3-one scaffold. A phenylthio group at the 2-position confers on the resulting derivative a high reactivity, which could be unmasked upon hydrolysis, and which led to the release of toxophoric thiophenol as detected by Ellman's reagent. Biological activity of these compounds was analysed towards various representative proteolytic enzymes. Pure diastereoisomers 7(R) and 7(S) displayed potent inhibitory activities against HIV-protease.

Graphical abstract: Parallel synthesis of new phenylalanino-2-(phenylthio)pyrrolidin-3-one scaffold-based analogues

Article information

Article type
Paper
Submitted
01 Feb 2002
Accepted
05 Mar 2002
First published
08 Apr 2002

J. Chem. Soc., Perkin Trans. 1, 2002, 1181-1189

Parallel synthesis of new phenylalanino-2-(phenylthio)pyrrolidin-3-one scaffold-based analogues

G. Quéléver, M. Bouygues and J. Kraus, J. Chem. Soc., Perkin Trans. 1, 2002, 1181 DOI: 10.1039/B201147F

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.

Spotlight

Advertisements