Exploring the enzyme ‐catalyzed synthesis of isotope labeled cyclopropanes

In this study, the use of enzyme-catalysis for the synthesis of labeled cyclopropanes was investigated. Two readily-available enzymes, a modified CYP450-enzyme and a modifiedAeropyrum pernic protoglobin, were investigated for the cyclopropanation of a variety of substituted styrenes. For this biocatalytic transformation, the enzymes required the use of ethyl diazoacetate. Due to the highly energetic nature of this molecule, alternatives were investigated. The final optimized cyclopropanation was successfully demonstrated usingn-hexyl diazoacetate, resulting in moderate to high enantiomeric excess. The optimized procedure was used to generate labeled cyclopropanes from13C-glycine, forming all four labeled stereoisomers of phosphodiesterase type IV inhibitor, MK0952. These reactions provide a convenient and effective biocatalytic route to stereoselective13C-labeled cyclopropanes and serve as a proof-of-concept for generating stereoselective labeled cyclopropanes.
Source: Journal of Labelled Compounds and Radiopharmaceuticals - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research