3 years ago

Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin

Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin
Elena P. Mirchink, Maria N Preobrazhenskaya, Elena B Isakova, Gennady B. Lapa

Abstract

Clarithromycin (active against Gram positive infections) and 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole derivatives (effective for Gram negative microbes) are the ligands of bacterial RNA. The antimicrobial activities of these benzoxaboroles linked with clarithromycin at 9 or 4″ position were compared. Two synthetic pathways for these conjugates were elaborated. First pathway explored the substitution of the C-9 carbonyl group of macrolactone’s cycle via oxime linker, the second direction used the modification of the 4″-O-group of cladinose via the formation of carbamates of benzoxaboroles. 4″-O-(3-S-(1-Hydroxy-1,3-dihydro-benzo[c][1,2]oxaborole)-methyl-carbamoyl-clarithromycin showed twofold decrease in MICs for S. epidermidis and S. pneumoniae than clarithromycin. 4″-O-Modified clarithromycin demonstrated an efficacy against Gram positive strains only. Compounds with C-9 substitution were more active than 4″-O-substituted antibiotics for susceptible strains E. coli tolC and did not exceed the activity of initial antibiotics.

Publisher URL: http://tandfonline.com/doi/full/10.1080/14756366.2016.1261129

DOI: 10.1080/14756366.2016.1261129

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