Synergy of synthesis, computation and NMR reveals correct baulamycin structures

Article

关键词: NATURAL-PRODUCTS;    CHEMICAL-SHIFTS;    BORONIC ESTERS;    ALDEHYDES;    ALLYLBORATION;    HYDROBORATION;    ANTIBIOTICS;    MOLECULES;    ALKENES;    H-1;   

DOI  :  10.1038/nature23265

来源: SCIE

【 摘 要 】

Small-molecule, biologically active natural products continue to be our most rewarding source of, and inspiration for, new medicines(1). Sometimes we happen upon such molecules in minute quantities in unique, difficult-to-reach, and often fleeting environments, perhaps never to be discovered again. In these cases, determining the structure of a molecule-including assigning its relative and absolute configurations-is paramount, enabling one to understand its biological activity. Molecules that comprise stereochemically complex acyclic and conformationally flexible carbon chains make such a task extremely challenging(2). The baulamycins (A and B) serve as a contemporary example. Isolated in small quantities and shown to have promising antimicrobial activity, the structure of the conformationally flexible molecules was determined largely through J-based configurational analysis(3,4), but has been found to be incorrect. Our subsequent campaign to identify the true structures of the baulamycins has revealed a powerful method for the rapid structural elucidation of such molecules. Specifically, the prediction of nuclear magnetic resonance (NMR) parameters through density functional theory-combined with an efficient sequence of boron-based synthetic transformations, which allowed an encoded (labelled) mixture of natural-product diastereomers to be prepared-enabled us rapidly to pinpoint and synthesize the correct structures.

【 授权许可】

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