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 chemoselectivity of the 3'-oxazaphospholidine derivatives was investigated by comparing them with the conventional nucleoside 3'-phosphoramidite.
Wada
Takeshi
T
Department 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
Maizuru
Yukihiro
Y
Shimizu
Mamoru
M
Oka
Natsuhisa
N
Saigo
Kazuhiko
K
D001895:Boron / Q000737:chemistry*; D015226:Dinucleoside Phosphates / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry*; D013237:Stereoisomerism
D015226:Dinucleoside Phosphates; D010080:Oxazoles; D001895:Boron