Stereoselective synthesis of dinucleoside boranophosphates by an oxazaphospholidine method
Takeshi Wada1, Yukihiro Maizuru, Mamoru Shimizu
1Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan. wada@k.u-tokyo.ac.jp
Abstract:
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 chemoselectivity of the 3'-oxazaphospholidine derivatives was investigated by comparing them with the conventional nucleoside 3'-phosphoramidite.
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