SONOCHEMICAL AND TRIETHYLBORANE-INDUCED TIN DEUTERIDE REDUCTION FOR THE HIGHLY DIASTEREOSELECTIVE SYNTHESIS OF (2'R)-2'-DEOXY[2'-H-2]RIBONUCLEOSIDE DERIVATIVES

For the NMR spectroscopic conformational analysis of a sugar moiety in a DNA complex with a protein or a drug, (2'R)- and/or (2'S)-2'-deoxy[ 2'-H-2]ribonucleoside derivatives with high purity are useful. To deve lop a highly diastereoselective and efficient method for the synthesis of(2'R)-2'-deoxy[2'-H-2]ribonucleoside derivatives, studies of leavin g groups (OPTC, Br) at the 2' position of nucleosides, of the effects of reaction temperature on diastereoselectivity, of radical generation (ultrasound irradiation, Et(3)B) at temperatures as low as -70 degree s C, and of protecting groups for the 3' and 5' hydroxyl groups (benzo ate, TPDS) of nucleosides were carried out. Bu(3)Sn(2)H-reductive deut eration of 3',5'-di-0-benzoyl-2'-bromo-2'-deoxyuridine under high-inte nsity ultrasound irradiation at -71 degrees C induced notably efficien t deuterium incorporation to afford a highly diastereoselective 3',5'- di-0-benzoyl-2'-deoxy[2'-H-2]uridin [(2'R):(2'S) = 96:4]. The use of E t(3)B, as an alternative radical generator, toward 2'-bromo-2'-deoxy-3 ',5'-0-TPDS-ribonucleosides at <--70 degrees C made it feasible to per form the reaction on a preparative scale, and provided excellent diast ereoselectivity (2'-deoxyadenosine, thymidine, and 2'-deoxyuridine der ivatives >99:1 which were converted to (2'R)-2'-deoxy[2'-H-2]cytidine derivatives, guanosine derivative = 91:9).