LABELED REPRESENTATIVES OF A POSSIBLE INTERMEDIATE OF FOSFOMYCIN BIOSYNTHESIS IN STREPTOMYCES-FRADIAE - PREPARATION OF (R,S)-(2-HYDROXYPROPYL)PHOSPHONIC, (R,S)-(2-HYDROXY-[1,1-H-2(2)]PROPYL)PHOSPHONIC, (R)-(2-HYDROXY-[1,1-H-2(2)]PROPYL)PHOSPHONIC AND (S)-(2-HYDROXY-[1,1-H-2](2)PROPYL)PHOSPHONIC AND (R,S)-(2-[O-18]HYDROXYPROPYL)PHOSPHONIC ACID

Racemic methyl O-benzyllactate was reduced to the alcohol, transformed into the bromide and reacted with triethylphosphite to give the diethylphosphonate. Removal of protecting groups afforded a phosphonic acid which was purified as its cyclohexylammonium salt. (S)-Ethyl and (R)-isobutyl O-benzyllactate were reduced with LiAlD4 to the corresponding dideuteriated alcohols, which were transformed in the same way as the racemic compound into the chiral (2-hydroxy-[1,1-H-2(2)]propyl)phosphonic acids. The optical purity of alcohols (S)- and (R)-6b was determined by derivatisation with (+)-MTPA-Cl and H-1-NMR-spectroscopy to be 98%. Exchange of the carbonyl-16-oxygen atom of 2-oxopropylphosphonate for oxygen-18 from (H2O)-O-18, reduction with NaBH4, deprotection and addition of cyclohexylamine yielded the salt (+/-)-18 of (2-[O-18]hydroxy-propyl)phosphonic acid.