Nucleic acid related compounds .94. Remarkably high stereoselective reductions of 2'- and 3'-ketonucleoside derivatives to give arabino, ribo, and xylofuranosyl nucleosides with hydrogen isotopes at C2' and C3'

Oxidation of 2',5'- and 3',5'-O-(tert-butyldimethylsilyl)-protected ribonucleosides gave the corresponding 3'-keto and 2'-keto derivatives, whose complete oxidation was assayed by total release of the heterocyclic base upon treatment with tetrabutylammonium fluoride/THF. Treatment of the protected ketones with sodium triacetoxyborohydride (generated in situ from sodium borohydride and acetic acid) in acetic acid resulted in hydride delivery at the a face with high stereoselectivity. The xylo/ribo (similar to 49:1) and arabino/ribo (similar to 49:1) diastereomers, respectively, were obtained in good to high overall yields upon deprotection. Selective removal of the TBDMS group from O5' (trifluoroacetic acid/water, 9:1, 0 degrees C) and treatment of these 5'-hydroxy-(3'- and 2')ketones with sodium triacetoxyborohydride effected remarkably selective delivery of hydride at the beta face. Deprotection gave the ribo/xylo (similar to 99:1) and ribo/arabino (similar to 99:1) nucleosides in high yields. Comparable results were obtained with sodium borodeuteride in acetic acid to give the four 2'[H-2] and 3'[2H] arabino, ribo, and xylo isotopomers with >95% incorporation of deuterium. Development of efficient procedures and comparisons with previous methods are discussed. Copyright (C) 1996 Elsevier Science Ltd