A convenient chemo-enzymatic synthesis and 18F-labelling of both enantiomers of trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane.
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.
Riss
Patrick Johannes
PJ
Institute of Nuclear Chemistry, Johannes Gutenberg-University Mainz, Fritz Strassmann-Weg 2, 55128, Mainz, Germany. riss@uni-mainz.de
Rösch
Frank
F
D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D004950:Esterases / Q000378:metabolism*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D013194:Staining and Labeling; D013237:Stereoisomerism; D013302:Streptomyces / Q000201:enzymology*; D013379:Substrate Specificity; D014050:Toluene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D003521:Cyclopropanes; D005462:Fluorine Radioisotopes; C534640:trans-1-toluenesulfonyloxymethyl-2-fluoromethyl-cyclopropane; C015766:cyclopropanecarboxylic acid; D014050:Toluene; D004950:Esterases