Pleuromutilin antibiotic

The mevalonate labelling pattern of the antibiotic pleuromutilin (5.130), which is produced by the Basidiomycete Pleurotus mutilus (Clitopilus scyphoides), suggests that it is formed (Scheme 5.12) by a more deep-seated rearrangement of a copalyl diphosphate (5.131 5.132 5.133). A derivative, tiamulin , is used in animal health and retapamulin (altabax ) has attracted interest because of its activity against resistant organisms where it selectively targets the bacterial ribosome. 

For a study of this strategy in the synthesis of the antibiotic pleuromutilin (isolated from the Basidiomycetes Pleurotus mutitus. active against Oram-positive bacteria) see ref 920. 

The antibiotic pleuromutilin (51), isolated from Pleurotus mutilis, has been synthesized by Gibbons. This neat synthesis has as its basis a sequential Michael strategy which produces in one step, i.e. (48) + (49) (50), the indane nucleus with four of the eight stereocentres of (51)... 

Retapamulin (26 Pleuromutilin (25) Antibiotic Semi-syntiietic Microbial Antibacterial Inhibits bacterial protein 294-303... 

Pleuromutilin (81 Scheme 28) an antibiotic isolated from several species of Basidiomycetes, e.g. Pleurotus mutilis, has been synthesized in a 30-step sequence. One of the most important steps is the fragmentation of (79) to generate the required tricyclic skeleton of this diteipene. Direct retroaldol ring opening of (79) to the respective diketone is unsuccessful, but a two-step sequence via the ketoallyl bromide (80) results in the desired transformation. 

Figure 4 Exemplar structures of various antibiotic classes that bind to either the 505 or the 305 subunit. Macrolides azithromycin (1), oxazolidinones linezolid (2), aminoglycosides Kanamycin A (3), Pleuromutilin (4), phenylpropanoids chloramphenicol (5), lincosamides clindamycin (6), Sparsomycin (7), Anisomycin (8), and tetracycline (9). See Scheme 9 for thiosptrepton (38). Not pictured streptogramins such as quinupristin/dalfopristin.

Pleuromutilin (Scheme 17.9) is an antibiotic from Pleurotus or Clitopilus basidiomycete strains which kills mainly Gram-positive bacteria and mycoplasms. Metabolism of pleuromutilin and derivatives results in hydroxylation by microsomal cytochrome P-450 at the 2- or 8-position and inactivates the antibiotics. Modification of the 8-position of pleuromutilin and analogs was of interest as a means of preventing the metabolic hydroxylation. Microbial hydroxylation at the... 

Pleuromutilin 81 (Eigure 16.20) is an antibiotic from Pleurotus or Clitopilus basidi-omycetes strains that kills mainly gram-positive bacteria and mycoplasms. A more... 

Pleuromutilin, a protein synthesis inhibitor, was first isolated from the genus Pleurotus and discovered as potent diterpene antibiotics in 1950. ° Later, several derivatives were discovered and have been used in veterinary and clinic environments. For example, tiamulin was the first pleuromutilin compound to be approved for veterinary use in 1979, followed by valnemulin in 1999. In 2007, retapamu-lin, a topical antibiotic developed by GlaxoSmithKline (London, U.K.), became the first pleuromutilin antibiotics approved for use in humans. It is marketed as an ointment under the brand names Altabax and Altargo. Retapamulin was approved by the U.S. Food and Drug Administration (FDA) for the treatment of bacterial skin infections such as... 

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