Scalable total synthesis and biological evaluation of haouamine A and its atropisomer

J Am Chem Soc. 2009 Jul 8;131(26):9172-3. doi: 10.1021/ja903745s.

Abstract

A total synthesis of the complex, bent aromatic ring-containing marine alkaloid haouamine A is achieved through a route in which every step (with the exception of the final deprotection) is performed on a gram-scale. This is accomplished through the development of a method for the dehydrogenation of cyclohexenones that allows for point-to-planar chirality transfer. This strategy makes it possible to program the desired atropisomeric outcome from a simple chiral cyclohexenone. By synthesizing atrop-haouamine A, this work has firmly established that natural haouamine exists as a single, nonequilibrating atropisomer. Finally, biological investigations demonstrate that the bent aromatic ring of this natural product is critical for anticancer activity against PC3 cells.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Heterocyclic Compounds, 4 or More Rings / chemical synthesis*
  • Heterocyclic Compounds, 4 or More Rings / chemistry
  • Heterocyclic Compounds, 4 or More Rings / pharmacology*
  • Humans
  • Male
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Prostatic Neoplasms / drug therapy
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds, 4 or More Rings
  • haouamine A