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Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A.

ABSTRACT: Molecular shape defines function in both biological and material settings, and chemists have developed an ever-increasing vernacular to describe these shapes. Noncanonical atropisomers-shape-defined molecules that are formally topologically trivial but are interconvertible only by complex, nonphysical multibond torsions-form a unique subset of atropisomers that differ from both canonical atropisomers (e.g., binaphthyls) and topoisomers (i.e., molecules that have identical connectivity but nonidentical molecular graphs). Small molecules, in contrast to biomacromolecules, are not expected to exhibit such ambiguous shapes. Using total synthesis, we found that the peptidic alkaloid tryptorubin A can be one of two noncanonical atropisomers. We then devised a synthetic strategy that drives the atropospecific synthesis of a noncanonical atrop-defined small molecule.

SUBMITTER: Reisberg SH

PROVIDER: S-EPMC6996792 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Total synthesis reveals atypical atropisomerism in a small-molecule natural product, tryptorubin A.

Reisberg Solomon H SH Gao Yang Y Walker Allison S AS Helfrich Eric J N EJN Clardy Jon J Baran Phil S PS

Science (New York, N.Y.) 20200102 6476

Molecular shape defines function in both biological and material settings, and chemists have developed an ever-increasing vernacular to describe these shapes. Noncanonical atropisomers-shape-defined molecules that are formally topologically trivial but are interconvertible only by complex, nonphysical multibond torsions-form a unique subset of atropisomers that differ from both canonical atropisomers (e.g., binaphthyls) and topoisomers (i.e., molecules that have identical connectivity but nonide ...[more]

PMID: 31896661

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