Synthesis and antibacterial activity of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether

Abstract

A series of new 400 -O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether were synthesized and evaluated for their in vitro antibacterial activity. All the desired compounds demonstrated favorable activity (0.03 lg ml -1 ) against erythromycin-susceptible Streptococcus pneumoniae comparable to the references, exhibiting 133-fold higher activity than precursor 2 or 3. Similarly, all of the analogs exhibited improved activity against the erythromycin-resistant S. pneumoniae encoded by the erm gene and the erm and mef genes, showing 4-32-fold more effectiveness than erythromycin A.

Cobalt-Catalyzed Cyclization of UnsaturatedN-Acyl Sulfonamides: a Diverted Mukaiyama Hydration Reaction

“…They have also been examined in drug discovery as prodrugs for esters and sulfonamides, addressing challenges associated with bioavailability and metabolism . While probenazole, a member of the class, has found applications as an antifungal agent against rice blast fungus and leaf blight, erythromycin derivatives modified through the incorporation of a cyclic imidate showed 4-fold increased activity against Streptococcus pneumoniae . Cyclic N -sulfonyl imidates are less well studied, despite the fact that they could be useful in a prodrug approach as precursors toward lactones.…”

A Validated RP-LC Method for the Determination of Erythromycin an Oxime and Related Substances

“…Reference substance EA was obtained from the National Institute for the Control of Pharmaceutical and Biological Products (Beijing, China). Reference of EAO, EAOZ, EAH and EAS were prepared according to literature procedures (Zhang et al, 2011). Figure 1 shows the structures of erythromycin A oxime and its related substances which resemble one another.…”

“…Erythromycin an Oxime (EAO) is a key intermediate in the synthesis of semi-synthetic macrolide antibiotic derivatives such as azithromycin, roxithromycin and clarithromycin (Wu and Su, 2001). It has been prepared by reaction of erythromycin A with hydroxylamine (Zhang et al, 2011). The following four related substances are formed during the reaction process: Z isomer of Erythromycin A Oxime (EAOZ), Erythromycin A (EA), Erythromycin A-6, 9-Hemiketal (EAH) and Erythromycin A-6, 9-9, 12-Spiroketal (EAS).…”