ABSOLUTE-CONFIGURATION OF THE ANTIVIRAL AGENT O-1-[2-HYDROXYMETHYL)-1,3-OXATHIOLAN-5-YL]CYTOSINE

The structure and absolute configuration of (-)-cis-5-(-)-cis-5-fluoro -1 -[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine (FTC), has been de termined by X-ray crystallographic analysis. The results confirm that the L-isomer of the nucleoside analogue is the most active enantiomer and that the correct absolute configuration of (-)-FTC is [2-hydroxyme thyl)oxathio-lan-5-yl]-fluorocytosine. The two molecules in the asymme tric unit show conformations that combine conformational features of t wo other classes of potent antiviral nucleosides. Both oxathiolane rin gs have the 3'-sulphur atom in nearly perfect S3'-exo envelope conform ations, similar to what is observed for 3'-azido-3'-deoxythymidine (AZ T) and 2',3'-dideoxycytidine. One of the two molecules has a glycosyli c link conformation in which the base is eclipsed with the C5'-O1' bon d. This mimics the high-anti conformation that has been observed in th e structures of several 2',3'-didehydro-2',3'-dideoxypyrimidine nucleo sides but is inaccessible for saturated pyrimidine nucleosides. Howeve r, the observed conformations cannot be superimposed adequately with o ther active antiviral nucleosides to suggest a common 'active site' co nformation.