Enantiomerically pure phosphonated carbocyclic 2'-oxa-3'-azanucleosides: synthesis and biological evaluation

Molecules. 2014 Sep 12;19(9):14406-16. doi: 10.3390/molecules190914406.

Abstract

Starting from enantiomeric pure 1-[(3S,5R)- and 1-[(3R,5S)-3-(hydroxymethyl)-2-methylisoxazolidin-5-yl]-5-methylpyrimidine-2,4(1H,3H)-diones (-)7a and (+)7b, obtained by lipase-catalyzed resolution, pure diethyl{[(3S,5R)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (-)12a and diethyl{[(3R,5S)-2-methyl-5-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)isoxazolidin-3-yl]methyl}phosphonate (+)12b have been synthesized. The obtained compounds showed no cytotoxic activity versus the U937 cell line in comparison with AZT, and were poorly able to inhibit HIV infection in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HIV / drug effects
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Humans
  • Molecular Structure
  • Nucleosides / chemical synthesis
  • Nucleosides / chemistry
  • Nucleosides / pharmacology*
  • Organophosphonates / chemical synthesis
  • Organophosphonates / chemistry
  • Organophosphonates / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship*
  • U937 Cells

Substances

  • Nucleosides
  • Organophosphonates