NUCLEIC-ACID RELATED-COMPOUNDS .94. REMARKABLY HIGH STEREOSELECTIVE REDUCTIONS OF 2'-KETONUCLEOSIDE AND 3'-KETONUCLEOSIDE DERIVATIVES TO GIVE ARABINO, RIBO, AND XYLOFURANOSYL NUCLEOSIDES WITH HYDROGEN ISOTOPESAT C2' AND C3'

Oxidation of 2',5'- and 3',5'-O-(tert-butyldimethylsilyl)-protected ri bonucleosides gave the corresponding 3'-keto and 2'-keto derivatives, whose complete oxidation was assayed by total release of the heterocyc lic base upon treatment with tetrabutylammonium fluoride/THF. Treatmen t of the protected ketones with sodium triacetoxyborohydride (generate d in situ from sodium borohydride and acetic acid) in acetic acid resu lted in hydride delivery at the a face with high stereoselectivity. Th e xylo/ribo (similar to 49:1) and arabino/ribo (similar to 49:1) diast ereomers, respectively, were obtained in good to high overall yields u pon deprotection. Selective removal of the TBDMS group from O5' (trifl uoroacetic acid/water, 9:1, 0 degrees C) and treatment of these 5'-hyd roxy-(3'- and 2')ketones with sodium triacetoxyborohydride effected re markably 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 so dium borodeuteride in acetic acid to give the four 2'[H-2] and 3'[2H] arabino, ribo, and xylo isotopomers with >95% incorporation of deuteri um. Development of efficient procedures and comparisons with previous methods are discussed. Copyright (C) 1996 Elsevier Science Ltd