SYNTHESIS OF 2',3'-DIDEOXY-3'-NITRO-2',3'-DIDEHYDROTHYMIDINE - ITS USES AS A GENERAL INTERMEDIATE FOR THE PREPARATION OF VARIOUS 2',3'-SUBSTITUTED NUCLEOSIDES

The first synthesis of 3-nitro-beta-D-glycero-pent-2-enofuranosyl)thym ine (7), is reported starting directly from 1-(beta-D-xylofuranosyl)th ymine (1). We also report a stereospecific conversion of (6) to 3'-nit ro-2',3'-dideoxythymidine (9). Detailed NMR studies have shown that th e solution conformation of 3'-nitro-2',3'-dideoxythymidine (9) is very similar to 3'-fluoro-2',3'-dideoxythymidine but the former is almost 100 fold less active than the later against HIV reverse transcriptase. Subsequently, the synthetic utilities of ideoxy-3-nitro-beta-D-glycer o-pent-2-enofuranosyl) thymine, (6) and (7), in the preparation of var ious 2'- and 3'-modified nucleosides have been established through Mic hael addition reactions with various oxygen, nitrogen and carbon nucle ophiles.