Christopher Williamson

The resolution and absolute stereochemistry of the enantiomers of cis-1-[2-(hydroxymethyl)1,3-oxathiolan-5-yl(cytosine (BCH189) : equipotent anti-HIV agents

Abstract Enzymic resolution of the monophosphate derivative of (/pm)-cis-1[2-(hydroxymethyl)-1, 3-oxathiolan-5-yl]cytosine using the 5′-nucleotidase from Crotalus atrox venom has allowed facile access to the individual enantimers. The absolute stereochemistry of the preferred (-)-enantiomer (8b) has been determined by X-ray crystallography of the bromine-contining derivative (10).

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.

Total synthesis of (–)-carbovir

Optically pure (–)-carbovir has been prepared by two different routes involving stereospecific opening of chiral cyclopentene epoxides by substituted purines. Introduction of the 2′,3′ unsaturation was accomplished by mesylate elimination, either after introduction of the purine (Route 1), or earlier in the sequence, producing a novel vinyl epoxide (Route 2).

Synthesis from (–)-aristeromycin and X-ray structure of (–)-carbovir

Efficient processes are described for the synthesis of (–)-carbovir 3 and its triphosphate derivative 28 from (–)-aristeromycin 4. The X-ray structure of (–)-carbovir has been determined.

Novel glucocorticoid antedrugs possessing a C16,17-fused γ-lactone ring

A series of novel γ-butyrolactones fused at the 16β,17β position of the 9α-fluoro-11β-hydroxy-3-oxoandrosta-1,4-diene nucleus and possessing oxygen substituents at 16α,17α positions were prepared and tested as glucocorticoid agonists. The compounds were also tested for their lability in human plasma. Lactone 5 was found to be rapidly hydrolysed in plasma, whereas derivative 18 was found to be a potent glucocorticoid agonist, but was stable in plasma. The structure of the C21S diastereoisomer of compound 18 was confirmed by an X-ray diffraction study.