A convenient chemo-enzymatic synthesis and 18F-labelling of both enantiomers of trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane

Org Biomol Chem. 2008 Dec 21;6(24):4567-74. doi: 10.1039/b812777h. Epub 2008 Oct 28.

Abstract

The present report is concerned with a stereoselective, reliable route to trans-1,2-disubstituted cyclopropanes and in particular to (S,S)-1-tosyloxymethyl-2-fluoromethyl-cyclopropane (1) and (R,R)-1-tosyloxymethyl-2-fluoromethyl-cyclopropane (ent-1) as conformationally restricted, terminally fluorinated C4-building blocks for medicinal chemistry. The enzymatic kinetic resolution based synthesis of 1 and ent-1 utilises inexpensive, commercially available starting materials. It is based on enantiomeric resolution of rac-cyclopropane carboxylic esters using esterase from Streptomyces diastatochromogenes. Both enantiomers of 1 were prepared selectively in high overall yield over nine steps, starting from ethyl acrylate. The successful radiosynthesis of [18F]-1 and [18F]-ent-1 is also reported.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Cyclopropanes / metabolism
  • Esterases / metabolism*
  • Fluorine Radioisotopes / chemistry*
  • Staining and Labeling
  • Stereoisomerism
  • Streptomyces / enzymology*
  • Substrate Specificity
  • Toluene / analogs & derivatives*
  • Toluene / chemical synthesis
  • Toluene / chemistry

Substances

  • Cyclopropanes
  • Fluorine Radioisotopes
  • trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane
  • cyclopropanecarboxylic acid
  • Toluene
  • Esterases