Markierte Vertreter eines möglichen Zwischenprodukts der Biosynthese von Fosfomycin inStreptomyces fradiae: Darstellung von (R,S)-(2-Hydroxypropyl)-, (R,S)-, (R)-, (S)-(2-Hydroxy-[1,1-2H2]propyl)-und (R,S)-(2-[18O]Hydroxypropyl)phosphonsäure

Summary 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-1,1-²H₂]propyl)phosphonic acids. The optical purity of alcohols (S)- and (R)-6 b was determined by derivatisation with (+)-MTPA-Cl and¹H-NMR-spectroscopy to be 98%. Exchange of the carbonyl-16-oxygen atom of 2-oxopropylphosphonate for oxygen-18 from H₂ ¹⁸O, reduction with NaBH₄, deprotection and addition of cyclohexylamine yielded the salt (±)-18 of (2-¹⁸O]hydroxypropyl)phosphonic acid.