A new DNA building block, 4'-selenothymidine: synthesis and modification to 4'-seleno-AZT as a potential anti-HIV agent

Org Lett. 2010 May 21;12(10):2242-5. doi: 10.1021/ol1005906.

Abstract

The first synthesis of 4'-selenothymidine (1), a novel DNA building block, and 4'-seleno-AZT (2) was accomplished from 2-deoxy-d-ribose via stereoselective formation of 2-deoxy-4-seleno-d-furanose 17 and a Pummerer-type base condensation as key steps. 4'-Selenothymidine (1) was discovered to adopt the same 2'-endo/3'-exo conformation as thymidine, which is unusual in that 4'-selenouridine has the opposite conformation to that of uridine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Crystallography, X-Ray
  • DNA / chemistry
  • DNA / drug effects*
  • HIV-1 / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Conformation
  • Organoselenium Compounds / chemical synthesis
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / pharmacology*
  • Thymidine / analogs & derivatives*
  • Thymidine / chemical synthesis
  • Thymidine / chemistry
  • Thymidine / pharmacology
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemical synthesis
  • Zidovudine / chemistry
  • Zidovudine / pharmacology

Substances

  • 4'-seleno-AZT
  • 4'-selenothymidine
  • Anti-HIV Agents
  • Organoselenium Compounds
  • Zidovudine
  • DNA
  • Thymidine