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′
✍ Scribed by Morris J. Robins; Sanchita Sarker; Vicente Samano; Stanislaw F. Wnuk
- Publisher
- Elsevier Science
- Year
- 1997
- Tongue
- French
- Weight
- 692 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0040-4020
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✦ Synopsis
Oxidation of 2',5'-and 3',5'-0.(terr-butyldimethylsilyl)-protected ribonucleosides gave rhe 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 cx face with high stereoselectivity.
The xylo/ribo (-49:l) and arabino/ribo (-49:l) diastereomers, respectively, were obtained in good to high overall yields upon deprotection. Selective removal of the TBDMS group from OS (trifluoroacetic acid/water, 9: 1, 0 "C) and treatment of these S-hydroxy-(3'-and 2')ketones with sodium triacetoxyborohydride effected remarkably selective delivery of hydride at the fi face. Deprotection gave the ribo/xylo (-99:l) and ribo/arabino (-99:l) nucleosides in high yields. Comparable results were obtained with sodium borodeuteride in acetic acid to give the four 2'[*H] and 3'[*H] arabino, ribo, and xylo isotopomers with >95% incorporation of deuterium. Development of efficient procedures and comparisons with previous methods are discussed.