Stereoselective synthesis of dinucleoside boranophosphates by an oxazaphospholidine method

A stereoselective synthesis of dinucleoside boranophosphates by using nucleoside 3'-oxazaphospholidine derivatives is described. The diastereoselectivity of the internucleotidic bond formation reactions varied with the nucleobase used. (Rp)- and (Sp)-dithymidine boranophosphates were synthesized with excellent diastereoselectivity both in solution and on a solid-support, whereas a loss of diastereopurity was observed for the 2'-deoxycytidine derivative having an unprotected nucleobase amino group. On the other hand, complete chemoselectivity of the 3'-oxazaphospholidine derivatives toward hydroxy groups over amino groups was serendipitously found during the study. This unique chemo selectivity of the 3'-oxazaphospholidine derivatives was investigated by comparing them with the conventional nucleoside 3'-phosphoramidite. (c) 2006 Elsevier Ltd. All rights reserved.