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

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.

SUBMITTER: Burns NZ

PROVIDER: S-EPMC2740483 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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

Burns Noah Z NZ Krylova Irina N IN Hannoush Rami N RN Baran Phil S PS

Journal of the American Chemical Society 20090701 26

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 atr ...[more]

PMID: 19530671

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