Nucleic acid related compounds. 41. Restricted furanose conformations of 3′,5′-O-(1,1,3,3-tetraisopropyldisilox-1,3-diyl)nucleosides provide a convenient evaluation of anomeric configuration

Abstract

Treatment of ribonucleosides (and related furanosyl compounds) with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in pyridine gave high yields of 3'',5''-O-(1,1,3,3-tetraisopropyldisilox-1,3-diyl)nucleosides (3'',5''-O-TPDS-nucleosides). The 1H NMR coupling parameters of the sugar backbone of the .beta.-D-ribofuranosyl anomers of these trans(1,2)-fused 8 to 5 membered ring TPDS compounds indicated a remarkably consistent range of furanose conformations. The data are compatible with a predominant population of conformers in the general 3E (C3''-endo) range found for a large series of rigidly trans-fused 6 to 5 membered ring nucleoside cyclic 3''-5''-monophosphates. X-ray crystallographic analysis of 3'',5''-O-TPDS-cytidine revealed an almost perfect 3E sugar envelope conformation (P = 19.7.degree., .tau.m = 41.9.degree.) in agreement with the 1H NMR solution data. Attachment of 2 bulky isopropyl groups to each silicon atom and expansion of the Si.sbd.O.sbd.Si bond angle to 155.degree. gives an essentially planar 6 atom segment of the 8-membered ring. Apparently, this demands a distinctly preferred conformation for the fused ring system. The readily prepared 3'',5''-O-TPDS-.beta.-D-ribofuranosyl derivatives have J1''-2'' .ltoreq. 1.5 Hz in most cases. This provides a rapid and convenient evaluation of the H1''-H2'' trans configuration in these structures.