2'-Azido-2',3'-dideoxythymidine: synthesis and crystal structure of a 2'-substituted dideoxynucleoside

Antiviral Res. 1990 Dec;14(6):357-69. doi: 10.1016/0166-3542(90)90054-b.

Abstract

1-(2-Azido-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine (2'-N3ddThd) was synthesized from 1-(5-O-trityl-2,3-anhydro-beta-D-lyxofuranosyl)thymine by two different procedures. Method A prepared the title compound by opening of the oxirane ring with LiEt3BH followed by mesylation of the 2'-hydroxyl function, introduction of the 2'-azido substituent and deblocking of the 5'-function. In method B nucleophilic opening of 3'-deoxy-5'-O-(tert-butyldimethylsilyl)-5-methyl-2,2'-anhydrouridine+ ++ was carried out with sodium azide in hexamethylphosphoramide in the presence of benzoic acid. Single X-ray crystallographic studies indicated a solid state conformation (3T2), which was opposite to that of the A form of AZT (2T3) but closely resembled that of 1-(2-fluoro-2,3-dideoxy-beta-D-erythropentofuranosyl)thymine (2'-FddThd) (3T2) and of 3'-azido-2',3'-dideoxy-2,6-diaminopurine riboside (3'-N3ddDAP) (3T2). Whereas the latter displayed significant inhibitory activity against human immunodeficiency virus (HIV) replication, 2'-FddThd and 2'-N3ddThd were essentially inactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis*
  • Crystallography
  • Dideoxynucleosides / chemistry
  • Dideoxynucleosides / pharmacology
  • HIV / drug effects*
  • Humans
  • In Vitro Techniques
  • Molecular Structure
  • Structure-Activity Relationship
  • Virus Replication / drug effects
  • X-Ray Diffraction
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemical synthesis
  • Zidovudine / chemistry

Substances

  • Antiviral Agents
  • Dideoxynucleosides
  • 2'-azido-2',3'-dideoxythymidine
  • Zidovudine
  • alovudine