AN EFFICIENT TOTAL SYNTHESIS OF CARBOCYCLIC 2'-DEOXYRIBONUCLEOSIDES

The present work describes a new and efficient method for the preparat ion of either racemic or enantiomerically pure carbocyclic 2'-deoxyrib onucleosides 1. Key steps are the efficient assembly of the racemic ca rbocyclic 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 syn thesis of enantiomerically pure and racemic carbocyclic 2'-deoxyribonu cleosides 1 represents one of the most efficient approaches reported t o date. Starting from cyclopentadiene, the four carbocycles correspond ing to the naturally occurring 2'-deoxyribonucleosides could be prepar ed in 12 steps and 9-12% overall yield. For the corresponding racemic compounds, 10 steps were used with overall yields between 22 and 30%.