1387556-29-7Relevant articles and documents
Precursor directed biosynthesis of an orthogonally functional erythromycin analogue: Selectivity in the ribosome macrolide binding pocket
Harvey, Colin J. B.,Puglisi, Joseph D.,Pande, Vijay S.,Cane, David E.,Khosla, Chaitan
, p. 12259 - 12265 (2012/09/22)
The macrolide antibiotic erythromycin A and its semisynthetic analogues have been among the most useful antibacterial agents for the treatment of infectious diseases. Using a recently developed chemical genetic strategy for precursor-directed biosynthesis and colony bioassay of 6-deoxyerythromycin D analogues, we identified a new class of alkynyl- and alkenyl-substituted macrolides with activities comparable to that of the natural product. Further analysis revealed a marked and unexpected dependence of antibiotic activity on the size and degree of unsaturation of the precursor. Based on these leads, we also report the precursor-directed biosynthesis of 15-propargyl erythromycin A, a novel antibiotic that not only is as potent as erythromycin A with respect to its ability to inhibit bacterial growth and cell-free ribosomal protein biosynthesis but also harbors an orthogonal functional group that is capable of facile chemical modification.
