BIOSYNTHESIS OF NATURAL-PRODUCTS WITH A P-C BOND .6. PREPARATION OF DEUTERIUM-LABELED AND CARBON-13-LABELED L-ALANYL-PHOSPHONIC AND L-ALANYL-L-ALANYL-(2-AMINOETHYL)PHOSPHONIC ACIDS AND THEIR USE IN BIOSYNTHETIC-STUDIES OF FOSFOMYCIN IN STREPTOMYCES-FRADIAE

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