Approaches to carbocyclic analogues of the potent neuraminidase inhibitor 4-guanidino-Neu5Ac2en. X-Ray molecular structure of N-[(1S,2S,6R)-2-azido-6-benzyloxymethyl-4-formylcyclohex-3-enyl]acetamide

Abstract

Various approaches using Diels–Alder chemistry have been established for the synthesis of truncated carbocyclic analogues 4 and 6 of 4-guanidino-Neu5Ac2en. In the case of compound 4, elaboration of an initial adduct from Danishefsky's diene and the dienophile 7 allowed access to the key enone 26. Methylenation of the carbonyl group and azide-induced opening of an intermediate oxazoline established the required framework regio- and stereo-specifically. Compounds 4 and 6 were found to retain interesting levels of antiviral activity comparable to those shown by their oxygen-containing counterparts.