Biosynthesis of natural products with a P–C bond. Part 6. Preparation of deuterium- and carbon-13-labelled L-alanyl- and L-alanyl-L-alanyl-(2-aminoethyl)phosphonic acids and their use in biosynthetic studies of fosfomycin in streptomyces fradiae

Abstract

(2-Aminoethyl)phosphonic acid (AEP) is not taken up by Streptomyces fradiae in the biosynthesis of fosfomycin. Attachment of L-alanine or L-alanyl-L-alanine to the amino group of deuteriated AEP affords di- and tri-peptides 4 and 5 which are transported into the cell.[2-¹³C]AEP is synthesized from Na¹³CN and the tosyloxymethylphosphonate 7. It is transformed into dipeptide 4d, which acts as a carrier for [2-¹³C]AEP which is incorporated into fosfomycin with an enrichment of 2%.