Penicillin biosynthesis: stereochemistry of desaturative and hydroxylative pathways from L-α-aminoadipoyl-L-cysteinyl-D-isodehydrovaline with isopenicillin N synthase

Abstract

Transformation of L-α-aminoadipoyl-L-cysteinyl-D-(Z)-[4-²H]isodehydrovaline (5b) and L-α-aminoadipoyl-L-cysteinyl-D-(E)-[4-²H]isodehydrovaline (5c) with isopenicillin N synthase gave rise to specifically deuteriated exomethylene cepham (6) and α-hydroxymethyl penam (7) products via the concomitant operation of stereospecific desaturative and hydroxylative ring closure pathways. The stereochemistries observed are in accord with competing ‘Ene’ and [2π+ 2π]cycloaddition of the proposed iron-oxo intermediate.