SYNTHESIS OF 2'-SPIRO-ISOXAZOLIDINE AND 3'-SPIRO-ISOXAZOLIDINE DERIVATIVES OF THYMIDINE AND THEIR CONVERSIONS TO 2',3'-DIDEOXY-2',3'-DIDEHYDRO-3'-C-SUBSTITUTED NUCLEOSIDES BY RADICAL PROMOTED FRAGMENTATION

We herein report the synthesis of a new class of 2'- and 3'-spiro-nucleosides (3 - 19, 38 - 55) by the 1,3-dipolar cycloaddition reaction of 2'- or 3-methylnitrone (2, 36 or 37) with ethyl vinyl ether and acrylonitrile. It has been also shown that the free-radical promoted deoxygenation of 3-hydroxy group vicinal to the 2'-spiro function in the free-radical precursor 15, 17 or 19 gives a mixture of 2',3'-dideoxy-2',3'-didehydro-2'-C-substituted thymidines (20, 21, 24 , 26, 28 or 32) and/or 2',3'-dideoxy-2'-spiro-derivatives (30). Similarly, the deoxygenation of 2'-hydroxy group vicinal to the 3'-spiro function in the free-radical precursor 49, 52 or 55 gives a mixture of 2',3'-dideoxy-2',3'-didehydro-3'-C-substituted nucleosides (59, 60 or 62) and/or 2',3'-dideoxy-3'-spiro-nucleosides (56 and 57). The results described herein constitute the first report of the synthesis of spiro-(1,2-isoxazolidine) derivatives of nucleosides and their use in the unique free-radical cleavage reactions to give 2',3'-dideoxy-2',3'-didehydro-C-branched nucleosides.