BIOSYNTHESIS OF NATURAL-PRODUCTS WITH A P-C BOND .7. SYNTHESIS OF [1,1-(H-2)2](2-HYDROXYETHYL)PHOSPHONIC, [2,2-(H-2)2](2-HYDROXYETHYL)PHOSPHONIC, (R)-[1-H-2](2-HYDROXYETHYL)PHOSPHONIC AND (S)-[1-H-2](2-HYDROXYETHYL)PHOSPHONIC ACID AND (R,S)-[1-H-2](1,2-DIHYDROXYETHYL)PHOSPHONIC ACID AND INCORPORATION STUDIES INTO FOSFOMYCIN IN STREPTOMYCES-FRADIAE

Nondeuteriated and deuteriated 2-(benzyloxy)ethanols (8a-c) were transformed into (2-hydroxyethyl)phosphonic acids (12a-c). 8c was prepared from dimethyl 2,3-O-isopropylidene-L-tartrate. 12b,c were fed to Streptomyces fradiae and were incorporated into fosfomycin (2), which was converted to amino phosphonic acid (-)-13. (-)-13 derived from 12b,c contained 42% and 34% deuterium, respectively. (1,2-Dihydroxyethyl)phosphonic acid ((+/-)-29) was not incorporated into fosfomycin. (S)- and (R)-(2-hydroxy[1-H-2-1]ethyl)phosphonic acids ((S)- and (R)-34) were prepared from (S)-2-(benzyloxy)[1-H-2-1]ethanol ((S)-30) and fed to S. fradiae. The deuterium of (R)-34 was lost, and the deuterium of (S)-34 was retained on incorporation into fosfomycin. The optical purity of (S)- and (R)-34 (84% and 86%, respectively) was determined by transformation to dimethyl ester and esterification with (+)-MTPA-Cl to afford 39b,c. 41 obtained from (S)-32 was identical with an authentic sample prepared from (S)-(2-amino[1-H-2-1]ethyl)phosphonic acid.