Rearranging the bicyclo[3.1.0]hexane template of carbocyclic nucleosides to improve binding recognition by kinases

Nucleosides Nucleotides Nucleic Acids. 2007;26(6-7):585-8. doi: 10.1080/15257770701490175.

Abstract

A novel bicyclo[3.1.0]hexane carbocyclic nucleoside (4) with a south-like conformation amenable to interact with the herpes thymidine kinase (HSV-tk) was synthesized with an endo-hydroxyl group positioned at the tip of the bicyclo[3.1.0]hexane ring system opposite to the tip of the fused cyclopropane ring. The introduction of the hydroxymethyl chain through a Baylis-Hillman type reaction and the regioselective opening of a cyclic sulfite intermediate to introduce the nitrogen functionality at the correct position are highlighted.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Bridged Bicyclo Compounds / chemical synthesis
  • Bridged Bicyclo Compounds / chemistry*
  • Nucleosides / chemical synthesis*
  • Nucleosides / chemistry
  • Protein Binding
  • Thymidine Kinase / metabolism*

Substances

  • Bridged Bicyclo Compounds
  • Nucleosides
  • bicyclo(3.1.0)hexane
  • Thymidine Kinase