Synthesis of AZTpSpCX2ppSA and AZTpSpCX2ppSAZT: hydrolysis-resistant potential inhibitors of the AZT excision reaction of HIV-1 RT

Org Lett. 2007 Dec 6;9(25):5243-6. doi: 10.1021/ol7023746. Epub 2007 Nov 8.


We report an efficient, one-flask route for synthesis of AZTpSpCX2ppSA and AZTpSpCX2ppSAZT, where X=H and X=F. This route makes use of the differential susceptibility to oxidation of H-phosphonate mono- and diesters, to allow a series of sequential reactions without requiring isolation of intermediates. These compounds are hydrolysis-resistant versions of the AZTppppA that results from excision of AZT by AZT-resistant HIV reverse transcriptase (RT). This family of compounds may therefore be useful in further study of the AZT excision reaction, as well as in drug design.

Publication types

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

MeSH terms

  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • Hydrolysis
  • Molecular Structure
  • Phosphates / chemistry
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Zidovudine / analogs & derivatives*
  • Zidovudine / chemical synthesis*
  • Zidovudine / chemistry


  • Phosphates
  • Reverse Transcriptase Inhibitors
  • Zidovudine
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase