Sonochemical and Triethylborane-Induced Tin Deuteride Reduction for the Highly Diastereoselective Synthesis of (2'R)-2'-Deoxyribonucleoside Derivatives

Article abstract of DOI:10.1021/jo00126a058

For the NMR spectroscopic conformational analysis of a sugar moiety in a DNA complex with a protein or drug, (2'R)- and/or (2'S)-2'-deoxy<2'-2H>ribonucleoside derivatives with high purity are useful.To develop a highly diastereoselective and efficient method for the synthesis of (2'R)-2'-deoxy<2'-2H>ribonucleoside derivatives, studies of leaving groups (OPTC, Br) at the 2' position of nucleosides, of the effects of reaction temperature on diastereoselectivity, of radical generation (ultrasound irradiation, Et3B) at temperatures as low as -70 deg C, and of protecting groups for the 3' and 5' hydroxyl groups (benzoate, TPDS) of nucleosides were carried out.Bu3Sn(2)H-reductive deuteration of 3',5'-di-O-benzoyl-2'-bromo-2'-deoxyuridine under high-intensity ultrasound irradiation at -71 deg C induced notably efficient deuterium incorporation to afford a highly diastereoselective 3',5'-di-O-benzoyl-2'-deoxy<2'-2H>uridine <(2'R):(2'S) = 96:4>.The use of Et3B as an alternative radical generator, toward 2'-bromo-2'-deoxy-3',5'-O-TPDS-ribonucleosides at <-70 deg C made it feasible to perform the reaction on a preparative scale, and provided excellent diastereoselectivity (2'-deoxyadenosine, thymidine, and 2'-deoxyuridine derivatives >99:1 which were converted to (2'R)-2'-deoxy<2'-2H>cytidine derivatives, guanosine derivative = 91:9).