Christopher Thomas Evans

Development of the biocatalytic resolution of 2-azabicyclo[2.2.1]hept-5-en-3-one as an entry to single-enantiomer carbocyclic nucleosides

Abstract For the resolution of the bicyclic lactam 2-azabicyclo[2.2.1]hept-5-en-3-one, efficient whole cell biocatalysts have been identified and from these, enzymes (lactamases) have been isolated. While the two enzymes obtained act on different enantiomers of the lactam, either can be used in scaleable processes to obtain synthons for carbocyclic nucleosides having the natural configuration.

Chemoenzymatic synthesis of (–)-carbovir utilizing a whole cell catalysed resolution of 2-azabicyclo[2.2.1]hept-5-en-3-one

The resolution of (±)-2-azabicyclo[2.2.1]hept-5-en-3-one (3), a versatile intermediate in the synthesis of carbocyclic nucleosides, is described; both optical forms of the lactam have been obtained in very high optical purity (> 98% enantiomeric excess) in rapid, facile, large-scale biotransformation processes using whole cell catalysts and the laevorotatory enantiomer has been converted into (–)-carbovir.

Potential use of carbocyclic nucleosides for the treatment of AIDS: chemo-enzymatic syntheses of the enantiomers of carbovir

The lactam (1R),(4S)-2-azabicyclo[2.2.1]hept-5-en-3-one [(–)-2], derived by whole cell enantio-specific hydrolysis of the racemate was converted into (–)-carbovir (–)-1 in ten steps. Lipase catalysed acetylation of 4-cis-hydroxycyclopent-2-enylmethyl triphenylmethyl ether afforded the optically pure ester (+)-3 and the alcohol (–)-9. The former compound was converted into (+)-carbovir (+)-1 in three steps.