Antibiotics, phosphorus-containing

Clindamycin (93 R = H), an antibiotic obtained by chlorinating linco-mycin, is converted by a species of Streptomyces into inactive phosphorus-containing compounds. These have been shown to be nucleoside 5 -phosphates derived from adenosine, cytidine, guanosine, and uridine. 

Phosphorus-containing sugar analogues have possible medicinal application in the treatment of obesity and diabetes, and also in the formulation of antiviral, antibiotic and antitumor agents (Section 6.25.5.2.1.ii) <94JOC2976>. 

The phosphorus-containing antibiotics represent an interesting and even more specialized group of naturally produced, true organophosphorus compounds many of them are of a peptide nature, the general methods of preparation of which will be considered in more detail in a later section, but fosmidomycin (105) is obtainable from Streptomyces species and currently undergoing clinical trials in human medicine. 

A phosphorus-containing antibiotic complex from Bacillus subtilis. Currently, four R. (A-D) are known with antifungal activities. The R. are hydrophilic and amphoteric. The main components are R. A (C11H22N5O4P, Mr 351.30) and R. B (C.sHj.NsO, , Mr 450.43). 

Huber, G., Moenomycin and related phosphorus-containing antibiotics, in Antibiotics, Vol 5, Part 1, Hahn, F.E., Ed., Springer-Verlag, New York, 1979, p. 135. 

A variety of cyclic phosphorus-containing structures have been synthesized and tested for their antibacterial and/or antifungal activities. There is a worldwide and urgent need for new antibiotics to counteract resistance mechanisms observed in many pathological bacterial or fungal strains. 

Bacitracin, a cyclic peptide, has been shown to block mucopeptide synthesis by inhibiting the dephosphorylation of a lipid pyrophosphate intermediate to lipid phosphate. It prevents the lipid carrier from further participating in the reaction cycle of peptidoglycan synthesis causing accumulation of the lipid pyrophosphate23a,b. The antibiotics enduramycin a (g, basic polypeptide), moenomycin b j d prasinomycin (two phosphorus containing antibiotics) are also inhibitors of mucopeptide synthesis. However, the specific reaction inhibited by these three antibiotics is still not well known. 

Attention is directed to the inhibition of cell wall biosynthesis by endurac idin, a basic polypeptide, and by the phosphorus containing antibiotics moenomycin and... 

Phosphorus-carbon compounds (natural products with a C-P bond). Many natural products contain phosphorus-oxygen-bonds, espec. metabolites of the primary metabolism. A few only contain the C-p bond, many of those show antibiotic activities. The first natural product of the C-P-type was aminoethylphos-phonic acid (AEP), discovered in 1959. Others, covered in this book are bialaphos, fosfazinomycin, fosfomycin, fosfonochlorin, phosphinothricin, phosphonothrixin and the rhizocticins. For a complete overview, see Ut.. ... 

Fosfomycin is one of a few natural products containing a carbon-phosphorus (C— P) bond isolated from Streptomyces fradiae, Streptomyces viridochromogenes, and Streptomyces wedmorensis [73]. It was also isolated from Pseudomonas syringae and Pseudomonas viridiflava [74, 75], Fosfomycin is a highly effective antibiotic of low toxicity clinically utilized for the treatment of lower urinary tract infections [76] as well as methicillin-resistant [77] and vancomycin-resistant [78] strains of S. aureus. Moreover, fosfomycin is effective for the treatment of cephalosporin- and penicillin-resistant Streptococcus pneumonia [79] and ciprofloxacin-resistant E. coli [80], The antimicrobial activity of fosfomycin has been ascribed to the inactivation of UDP-GlcAAc-3-O-enolpyruvyltransferase (MurA), an essential enzyme that catalyzes the first committed step in the biosynthesis of peptidoglycan, the main component of the cell wall, by covalent alkylation of an active site cysteine [81]. 

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