Anomalous Chromophore Disruption Enables an Eight-Step Synthesis and Stereochemical Reassignment of (+)-Marineosin A

J Am Chem Soc. 2019 Feb 13;141(6):2274-2278. doi: 10.1021/jacs.9b00396. Epub 2019 Jan 31.

Abstract

An eight-step asymmetric synthesis of (+)-marineosin A is described. The route proceeds by condensing fragments of reversed polarity relative to conventional prodiginine constructions. The resultant unstable chromophore is disrupted by a unique cycloisomerization promoted at a tailored manganese surface. This provides a premarineosin and subsequently marineosin A in a particularly concise manner. A pyridinophane N-oxide photorearrangement in flow and structural isomers of premarineosin are discussed, as is the reassignment of marineosin stereochemistry. The route gives access to the natural product as well as diastereomers, congeners and analogs that are currently inaccessible by other means.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chemistry Techniques, Synthetic
  • Hydrogenation
  • Models, Molecular
  • Molecular Conformation
  • Photochemical Processes
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry*
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry*
  • Stereoisomerism

Substances

  • Pyrroles
  • Spiro Compounds
  • marineosin A