An efficient, general asymmetric synthesis of carbocyclic nucleosides: application of an asymmetric aldol/ring-closing metathesis strategy

J Org Chem. 2000 Dec 15;65(25):8499-509. doi: 10.1021/jo005535p.

Abstract

A general and efficient synthesis of carbocyclic and hexenopyranosyl nucleosides has been developed. The strategy combines three key transformations: an asymmetric aldol addition to establish the relative and absolute configuration of the pseudosugar, a ring-closing metathesis to construct the pseudosugar ring, and a Trost-type palladium(0)-mediated substitution to assemble the pseudosugar and the aromatic base. Carbovir, abacavir, and their 2'-methyl derivatives as well as hexenopyranosyl nucleoside analogues have been prepared by this sequence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Dideoxynucleosides / chemical synthesis
  • Dideoxynucleosides / chemistry
  • Magnetic Resonance Spectroscopy
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry
  • Spectrophotometry, Infrared

Substances

  • Antiviral Agents
  • Dideoxynucleosides
  • Nucleosides
  • carbovir
  • abacavir