Synthesis using ring closure metathesis and effect on nucleoside transport of a (N)-methanocarba S-(4-nitrobenzyl)thioinosine derivative

Org Lett. 2001 Feb 22;3(4):597-9. doi: 10.1021/ol006999c.

Abstract

[reaction: see text] A new synthetic route to ring-constrained (N)-methanocarba nucleosides and nucleotides is presented. Ring closure of a diene intermediate using Grubbs catalyst provides a new avenue for the preparation of the cyclopentenone derivative 6, which is a versatile intermediate for various carbocycles. The product was almost as potent an inhibitor of es-mediated nucleoside transport as the parent compound, inhibiting initial rates of uptake of uridine into cultured CCRF-CEM cells by 50% at approximately 30-50 nM.

MeSH terms

  • Biological Transport / drug effects*
  • Catalysis
  • Cells, Cultured
  • Cyclization
  • Cyclopentanes / chemistry*
  • Humans
  • Molecular Structure
  • Nucleotides / metabolism*
  • Structure-Activity Relationship
  • Thioinosine / analogs & derivatives*
  • Thioinosine / chemistry

Substances

  • Cyclopentanes
  • Nucleotides
  • cyclopentanone
  • Thioinosine
  • 4-nitrobenzylthioinosine