Designer macrolides

A gene designated msrA has been identified in Staph, aureus which confers resistance to macrolides and streptogramins but not to lincosamides. Its function is unknown but the DNA sequence is homologous to genes coding for known efflux proteins. 

Two-level full factorial designs were used to determine the CE robusmess of a chiral separation of the local anesthetic ropivacaine in injection solutions and of a separation of the macrolide antibiotic tylosin and its main related substances. Table 13a shows the applied... 

The four-plate test was initially based on the German Hemmstoff-test with an additional plate of Sarcina lulea at pH 8.0, designed for the detection of lower levels of macrolides, and a fourth plate of Escherichia coli at pH 7.2 for the detection of sulfonamides (74,75). The modified version adopted by the European Community for screening carcasses is based on three plates with Bacillus subtilis BGA at pH values of 6.0, 8.0, and 7.2 with added trimethoprim, respectively, and a fourth plate with Micrococcus luteus NCTC 8340 at pH 8.0 (74). This test as described elsewhere (76) is intended to detect residues of -lactams, tetracyclines, aminoglycosides, sulfonamides, and macrolides in muscle tissue of slaughtered animals, without any prior extraction or cleanup. 

Borisova SA, Zhao L, Sherman DH et al (1999) Biosynthesis of desosamine construction of a new macrolide carrying a genetically designed sugar moiety. Org Lett 1 133-136... 

S. antibioticus produces another unusual macrolide antibiotic [45] called chlorothricin (57) containing, in addition to the aglycone (modified methylsalicylic acid), saccharides, dideoxyhexoses in the first place. Their biosynthesis was investigated by the incorporation of stable isotopes [45-47]. The compounds were only active in a synthetic medium and inactive in a complex one [48]. Compounds designated MC031-034 (58-61) are similar to chlorothricin mentioned above and were isolated from the cultivation broth of Streptomyces sp. collected in Japan. Another compound, 2-hydroxychlorothricin (62), with antitumor activity, was isolated [66] from Streptomyces K818. 

For a review, in English, of computer-aided conformational design in macrolide synthesis (including carbonolides) see O. Yonemitsu, Yuki Gosei Kagaku Kyokaishi, 1994, 52, 946. 

Zotchev SB, Stepanchikova AV, Sergeyko AP, Sobolev BN, Filimonov DA, Poroikov VV (2006) Rational Design of Macrolides by Virtual Screening of Combinatorial Libraries Generated Through in silico Manipulation of Polyketide Synthases. J Med Chem 49 2077... 

In their landmark total synthesis of polyene macrolide Amphotericin B [92], Nicolaou and coworkers designed a mycosamine precursor 57 and coupled it with a highly functionalized aglycon (O Scheme 32). Inversion of the C2-OH followed by the azide reduction and deprotections competed the total synthesis. 

In the screening of marine streptomycete isolates for bioactive components, a new macrolide antibiotic designated as chalcomycin B 258... 

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