Transannular [6 + 4] and Ambimodal Cycloaddition in the Biosynthesis of Heronamide A.

The transannular [6 + 4] cycloaddition proposed as a step in the biosynthesis of heronamide A has been modeled using density functional theory. The proposed cycloaddition is highly stereoselective, affording a single product. The reaction proceeds through an ambimodal transition state that directly...

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Published in:Journal of the American Chemical Society Vol. 137; no. 42; pp. 13518 - 13524
Main Authors: Peiyuan Yu, Patel, Ashay, Houk, K. N.
Format: Article
Published: American Chemical Society 10/28/2015
Subjects:
Online Access:View this record in EBSCOhost
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      dt: 10/28/2015
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      pub: American Chemical Society
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        110948474
        10.1021/jacs.5b06656
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        atl: Transannular [6 + 4] and Ambimodal Cycloaddition in the Biosynthesis of Heronamide A.
      aug:
        au:
          Peiyuan Yu
          Patel, Ashay
          Houk, K. N.
        affil:
          Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States
          Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, United States
      su:
        Ring formation (Chemistry)
        Biosynthesis
        Amides
        Density functional theory
        Biochemical substrates
        Thermodynamics
      sug:
        subj:
          Ring formation (Chemistry)
          Biosynthesis
          Amides
          Density functional theory
          Biochemical substrates
          Thermodynamics
      ab: The transannular [6 + 4] cycloaddition proposed as a step in the biosynthesis of heronamide A has been modeled using density functional theory. The proposed cycloaddition is highly stereoselective, affording a single product. The reaction proceeds through an ambimodal transition state that directly leads to a [4 + 2] adduct in addition to the observed [6 + 4] adduct. Interconversion of these adducts is possible via a facile Cope rearrangement. The [6 + 4] adduct is thermodynamically more stable than the [4 + 2] adduct by 5.2 kcal mol due to a combination of the ring and steric strain in the [4 + 2] product. The results strongly support the plausibility of the proposed transannular [6 + 4] cycloaddition in the biogenesis of heronamide A and may provide insights to designing substrates that selectively undergo [6 + 4] cycloaddition to form unbridged 10-membered rings.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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