Niall Galbraith Weir

The synthesis and antiviral activity of 4-fluoro-1-beta-D-ribofuranosyl-1H-pyrazole-3-carboxamide.

A novel fluoropyrazole ribonucleoside has been shown to have significant anti-influenza activity in vitro. The compound is compared and contrasted with the structurally-related compound ribavirin in attempts to identify factors having significant bearing on the mode of action of both compounds.

Synthesis of the potent influenza neuraminidase inhibitor 4-guanidino Neu5Ac2en. X-Ray molecular structure of 5-acetamido-4-amino-2,6-anhydro-3,4,5-trideoxy-D-erythro-L-gluco-nononic acid

An efficient and high-yielding synthesis of 4-guanidino Neu5Ac2en, the potent anti-influenza A and B compound, is described. The route exploits a stereospecific introduction of the key nitrogen functionality at C-4 via an oxazoline intermediate. Three different methods for the final-step conversion of the 4-amino into 4-guanidino derivatives are described. To explore the structure–activity relationship in this region of the molecule, a series of substituted guanidino derivatives were synthesized and their activity is described.

Synthesis of 6-, 7- and 8-carbon sugar analogues of potent anti-influenza 2,3-didehydro-2,3-dideoxy-N-acetylneuraminic acid derivatives

Analogues of the potent anti-influenza A and B compound, 4-guanidino-Neu5Ac2en, are described in which the stereochemically demanding C-6-glycerol side-chain is truncated. Syntheses of the one- and two-carbon side-chain analogues, of both 4-guanidino- and 4-amino-Neu5Ac2en, are presented, as well as the syntheses of analogues lacking any side-chain. Whilst complete removal of the C-6 side-chain abolishes activity, a stepwise increase in inhibition of influenza neuraminidase and influenza A and B in cell culture with increasing C-6 chain length is observed. The one-carbon, hydroxymethyl derivative retains significant activity to represent a suitable lead in the search for neuraminidase inhibitors of reduced stereochemical demand and synthetic complexity.

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

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 Danishefskys 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.

Synthesis and Biological Activity of Carbocyclic Clitocine

Abstract The preparation and anti-viral activity of carbocyclic clitocine and some related compounds are described.