Stereoselective Syntheses of Deuterated Pipecolic Acids as Tools to Investigate the Stereoselectivity of the Hydroxylase GetF

Abstract

Members of the GE81112 family are interesting candidates for the development of antibiotics. The configuration of the OH group on the pipecolic acid moiety plays a pivotal role in antibiotic activity. To investigate the stereoselectivity of the corresponding hydroxylase GetF, involved in the biosynthetic pathway, we synthesized the two deuterium-labeled pipecolic acid diastereomers in a highly stereoselective fashion via chelate-enolate Claisen rearrangement. The stereochemical outcome of the enzymatic hydroxylation step could easily be determined by analysis of mass differences between the products.