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.
Woschek
Anna
A
Institut für Organische Chemie, Universität Wien, Währingerstrasse 38, 1090 Vienna, Austria.
Wuggenig
Frank
F
Peti
Wolfgang
W
Hammerschmidt
Friedrich
F
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001711:Biotransformation; D003903:Deuterium; D004852:Epoxy Compounds / Q000378:metabolism; D005578:Fosfomycin / Q000096:biosynthesis*; D010728:Phosphoenolpyruvate / Q000378:metabolism*; D011849:Radioactive Tracers; D013237:Stereoisomerism; D013302:Streptomyces / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D004852:Epoxy Compounds; D011849:Radioactive Tracers; D005578:Fosfomycin; D010728:Phosphoenolpyruvate; D003903:Deuterium