On the transformation of (S)-2-hydroxypropylphosphonic acid into fosfomycin in Streptomyces fradiae--a unique method of epoxide ring formation.

(1S,2S)- and (1R,2S)-2-hydroxy-[1-D(1)]propylphosphonic acid were synthesised from (1S,2S)-2-benzyloxy-[1-D(1)]propanol, which was obtained by horse liver alcohol dehydrogenase catalysed reduction of the corresponding aldehyde. When (1S,2S)-2-hydroxy-[1-D(1)]propylphosphonic acid was fed to Streptomyces fradiae, the deuterium was retained to the same extent in fosfomycin (cis-epoxide) and its co-metabolite trans-epoxide. Removal of the hydrogen (deuterium) atom from the C-1 atom of deuterated 2-hydroxypropylphosphonic acids is a stereospecific process (the hydrogen atom of (S)-2-hydroxypropylphosphonic acid is pro-R). The formation of the O--C-1 bond of fosfomycin occurs with net inversion of configuration, the formation of the O--C-1 bond of the trans-epoxide with net retention.