Phosphonomycin

Bacillus cereus degrades (45) to acetaldehyde with fission of the C—P bond. An enzyme which catalyses the decomposition of phosphono-acetaldehyde (47), an intermediate in this degradation to acetaldehyde, has been characterized. The enzyme will only degrade (47) and will not breakdown a number of other phosphonates, including phosphonomycin (48).  

Phosphonomycin.—Since the publication of the synthesis of (48), which was described in last year s Report, numerous patents have been filed of syntheses of this antibiotic. The isomerization of the trans- 

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C. Rearrangements.—The thermal rearrangement of di-t-butyl-2-propynyl phosphite (95) has been used in a new synthesis of phosphonomycin (96)." The half salt (97) was obtained optically pure after a single crystallization. 

McGrath JW, F Hammerschmidt, P Quinn (1998) Biodegradation of phosphonomycin by Rhizobium huakuii PMYl. Appl Environ Microbiol 64 356-358. 

An example of the synthetic use of allene hydrogenation is the preparation of the antibiotic phosphonomycin (equation 47)124. 

Dialkyl vinylphosphonates.13 Pd(0) catalyzes the reaction of vinyl bromides and dialkyl phosphites in the presence of trielhylamine (1 equivalent) to form dialkyl vinylphosphonates. The configuration of the starting material is retained. An example is the synthesis of phosphonomycin (1, equation I). 

The first stage of cell wall synthesis formation of UDP-A-acetylmuramyl-pentapeptide (full structure shown at bottom). Point of inhibition by the antibiotic phosphonomycin are indicated. 

In addition to penicillin several other antibiotics (phosphonomycin, bacitracin, and vancomycin) block cell wall synthesis at different locations (see figs. 16.16 and 16.17). In addition to their biological and medical importance, these antibiotics have been very useful in elucidating the biosynthetic pathway. This is because they cause accumulation of the intermediate before the blocked step. This species can frequently be isolated and confirmed as a genuine intermediate in the pathway. 

Fosfomycin trometamol, a stable salt of fosfomycin (phosphonomycin), inhibits a very early stage of bacterial cell wall synthesis (Figure 43-5). An analog of phosphoenolpyruvate, it is structurally unrelated to any other antimicrobial agent. It inhibits the cytoplasmic enzyme enolpyruvate transferase by covalently binding to the cysteine residue of the active site and blocking the addition of phosphoenolpyruvate to UDP-V-acetylglucosamine. This reaction is the first step in the... 

Chemical Name (cis-l,2-Epoxypropyl)phosphonic acid Common Name Phosphonomycin Structural Formula ... 

Initially, /-menthyl 2-cyano-3-methyI-2-pentenoate, and /-menthyl and r/-bornyl cy-clopentylidenecyanoacetateswere epoxidized with hydrogen peroxide in the presence of sodium tungstate. Some asymmetric induction was achieved, but the degree of diastereoselectivity was not estimated26. In the final step of the synthesis of the antibiotic phosphonomycin, (Z)-propenylphosphonic acid was epoxidized under Weitz-Scheffer conditions and 92% optically pure phosphonomycin (+ )-x-phenethylammonium-c -epoxypropylphosphonate crystallized from the reaction mixture. It is unclear whether an asymmetric induction occurs during the epoxidation step and to what extent27. 

Phenylp-tolueneselenosulfonate, 315 Phenyl trimethylsilyl selenide, 438, 439 Phenyl vinyl sulfone, 170, 315-316 Phosphonomycin, 390 Phosphoric acid, 317 Phosphoric acid-Formic acid, 317-318 Phosphorus(III) chloride, 318 Phosphorus(III) iodide, 318-319 Phosphorus(V) oxide, 319 Phosphorus(V) sulfide, 320 Phthalides, 383... 

Fosfomycin, the (IR,IS) (-)-l,2-cpoxy propylphosphonic acid, formerly called phosphonomycin, is a low-molecular-weight antibiotic of unusual structure that was originally isolated in 1969 from used culture medium of Streptomyces fradiae (Figure 4.l),i. 86-i88 yjjg structure was established by... 

Penz, G., and Zbiral, E., Synthesis of dialkyl ( )-cZ5-l,2-epoxy-3-oxoalkylphsphonates. Phosphonomycin analogues, Monatsh. Chem., 113, 1169, 1982. 

Phosphonomycin,—Yet another synthesis of phosphonomycin (22) has appeared (Scheme 6). The phosphonoaldehyde (23) was treated with pentan-3-one and cyclohexylamine to give (24), which was then converted into its oxime. Tosylation of this oxime followed by treatment with bicarbonate caused the molecule to fragment, liberating the dimethyl ester of (22). Disodium phosphonoacetic acid when administered orally or topically to mice infected with Herpes simplex virus will reduce significantly the mortality of mice caused by this virus. JV-Phosphonomethyl-glycine is a promising herbicide. Recent work has shown that it exerts its effect by inhibiting the biosynthesis of aromatic amino-acids. ... 

Allenes with a terminal double bond are selectively reduced in the terminal position, e.g., in the synthesis of the antibiotic phosphonomycin, 5. Here the catalyst is selective and is also highly stereospecific. The reduced product is pure phosphonomycin ... 

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