AN EFFICIENT TOTAL SYNTHESIS OF CARBOCYCLIC 2'-DEOXYRIBONUCLEOSIDES

The present work describes a new and efficient method for the preparation of either racemic or enantiomerically pure carbocyclic 2'-deoxyribonucleosides 1. Key steps are the efficient assembly of the racemic carbocyclic 2'-deoxyribose core (+/-)-12, its enzymatic resolution, and a new approach to covalently link the purine and pyrimidine bases with the cyclopentane moiety via the cyclic sulfate (+)-19. This total synthesis of enantiomerically pure and racemic carbocyclic 2'-deoxyribonucleosides 1 represents one of the most efficient approaches reported to date. Starting from cyclopentadiene, the four carbocycles corresponding to the naturally occurring 2'-deoxyribonucleosides could be prepared in 12 steps and 9-12% overall yield. For the corresponding racemic compounds, 10 steps were used with overall yields between 22 and 30%.