Expeditious syntheses of sugar-modified nucleosides and collections thereof exploiting furan-, pyrrole-, and thiophene-based siloxy dienes

J Med Chem. 1997 Jan 17;40(2):168-80. doi: 10.1021/jm960400q.

Abstract

A series of individual sugar-modified pyrimidine nucleosides including enantiomerically enriched 2',3'-dideoxynucleosides 14a-c (alpha and beta anomers of L- and D-series), 2',3'-dideoxy-4'-thionucleosides 21a-c (alpha and beta anomers of L- and D-series), and 2',3'-dideoxy-4'-azanucleosides 28a-c (beta anomers of L- and D-series) were synthesized, with uniform chemistry and high stereochemical efficiency, exploiting a triad of versatile heterocyclic siloxy dienes, namely, 2-(tert-butyldimethylsiloxy)furan (TBSOF), 2-(tert-butyldimethylsiloxy)thiophene (TBSOT), and N-(tert-butoxycarbonyl)-2-(tert-butyldimethylsiloxy)pyrrole (TBSOP). The synthetic procedure advantageously used both enantiomers of glyceraldehyde acetonide (D-1 and L-1) as sources of chirality and as synthetic equivalents of the formyl cation. The outlined chemistry also allowed for the rapid assemblage of a 30-member collection of racemic nucleosides (D,L-L) as well as one 15-member ensemble of chiral analogues (L-L), along with some related sublibraries.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Furans / chemical synthesis*
  • Nucleosides / chemical synthesis*
  • Pyrroles / chemical synthesis*
  • Silicon Compounds / chemical synthesis*
  • Stereoisomerism
  • Thiophenes / chemical synthesis*

Substances

  • Furans
  • Nucleosides
  • Pyrroles
  • Silicon Compounds
  • Thiophenes