Title

Synthesis of Cyclopentenyl Carbocyclic Nucleosides as Potential Antiviral Agents Against Orthopoxviruses and SARS

Document Type

Article

Journal/Book Title/Conference

Journal of Medicinal Chemistry

Volume

49

Issue

3

Publisher

American Chemical Society

Publication Date

2006

First Page

1140

Last Page

1148

DOI

10.1021/jm0509750

Abstract

A practical and convenient methodology for the synthesis of chiral cyclopentenol derivative (+)-12a has been developed as the key intermediate that was utilized for the synthesis of biologically active carbocyclic nucleosides. The selective protection of allylic hydroxyl group followed by the ring-closing metathesis (RCM) reaction with Grubbs catalysts provided (+)-12a on a 10 g scale with 52% overall yield from d-ribose (4). The key intermediate (+)-12a was utilized for the synthesis of unnatural five-membered ring heterocyclic carbocyclic nucleosides. The newly synthesized 1,2,3-triazole analogue (17c) exhibited potent antiviral activity (EC50 0.4 μM) against vaccinia virus and moderate activities (EC50 39 μM) against cowpox virus and severe acute respiratory syndrome coronavirus (SARSCoV) (EC50 47 μM). The 1,2,4-triazole analogue (17a) also exhibited moderate antiviral activity (EC50 21 μM) against SARSCoV.