Combating multidrug-resistant bacteria is one of the grand health challenges of the new millennium. The Center for Disease Control and Prevention recently reported that annually over 2 million Americans are infected by such pathogens; at least 23,000 infections are fatal. Resistance has been observed to every antibiotic that is currently on the market, even to our most important drug-of-last resort, vancomycin. Traditionally, synthetic tailoring has allowed us to repurpose ineffective antibiotics and reintroduce more effective derivatives back into the clinic. This approach has been successfully employed with nearly all antibiotic families on the market. Because of its structural complexity; however, synthetic tailoring is not feasible with vancomycin. Herein, we propose a new platform for developing useful vancomycin analogs, thus allowing us to repurpose this drug. In this chemo-enzymatic approach, synthetic routes generate the monomeric units, while the macrocycles are formed using the biosynthetic enzymes, thus mirroring the natural biogenesis of these molecules (Figure 1).

Chemo-enzymatic approach towards the synthesis of vancomycin and its analogs

253rd National Meeting (2017)

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