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Bioinspired synthesis of a lactam analogue of abyssomicin C
A Cole Edwards1, Joshua G Pierce1
1Department of Chemistry, Comparative Medicine Institute, and Integrative Sciences Initiative, NC State University, Raleigh, NC 27607, USA.
Abstract:
The bioinspired approach to abyssomicin C developed by Sorensen has been utilized to prepare a novel analog containing an α, β-unsaturated lactam. This synthesis was designed to utilize the intramolecular Diels-Alder reaction in late-stage synthesis to provide analogs that contain deep-seated modifications to explore their antimicrobial properties. Overall, installing this non-natural lactam moiety was successful and allowed for antimicrobial assessment of the analog, but the low yields highlight the frequent challenges of leveraging a bioinspired approach for a new-to-nature molecular target.
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The DCC-promoted synthesis of amides begins with the protonation of DCC by carboxylic acid. The protonation makes it a better acceptor. Next, the addition of carboxylate to the protonated carbodiimide gives a reactive acylating agent.
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