[Stereochemistry of substituting the allyl hydroxyl group with fluorine atom in prostaglandins. Synthesis of 15-fluoro-11,15-dideoxyprostaglandins E1]

Bioorg Khim. 1996 Oct-Nov;22(10-11):814-22.
[Article in Russian]

Abstract

(+/-)-15-Fluoro-11,15-dideoxyprostaglandin E1 and its methyl and ethyl esters were synthesized. Dehydroxyfluorination reaction (+/-)-11-deoxyprostaglandin E1 esters with various reagents based on SF4 was studied. Along with the target 15-fluorides (mixtures of alpha- and beta-epimers), products of allylic shift and dehydration in a ratio dependent on the fluorination agent were shown to be formed. With a morpholinotrifluorosulfuran-tris(morpholine)sulfonium trimethyldifluorosilicate mixture, the maximal excess (70%) of one of the 15-fluoro epimers was achieved. Possible mechanisms of dehydroxyfluorination of (+/-)-11-deoxyprostaglandin E1 esters with dialkylaminoflluorosulfurans were proposed. Methyl esters of 15-alpha-fluoro- and 15-beta-fluoro-11,15-dideoxyprostaglandin E1 exhibited moderate antiaggregation activity in rabbit platelet tests.

Publication types

  • English Abstract

MeSH terms

  • Alprostadil / analogs & derivatives*
  • Alprostadil / chemical synthesis
  • Alprostadil / chemistry
  • Alprostadil / pharmacology
  • Animals
  • In Vitro Techniques
  • Platelet Aggregation Inhibitors / chemical synthesis*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology
  • Rabbits
  • Stereoisomerism

Substances

  • 15-fluoro-11,15-dideoxyprostaglandin E1
  • Platelet Aggregation Inhibitors
  • Alprostadil