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Synergy of synthesis, computation and NMR reveals correct baulamycin structures

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)436-440
Number of pages5
JournalNature
Volume547
Issue number7664
Early online date26 Jul 2017
DOIs
DateAccepted/In press - 31 May 2017
DateE-pub ahead of print - 26 Jul 2017
DatePublished (current) - 26 Jul 2017

Abstract

Small-molecule, biologically active natural products continue to be our most rewarding source of, and inspiration for, new medicines. 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. 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, 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.

    Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Springer Nature at https://www.nature.com/articles/nature23265. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 1 MB, PDF-document

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