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Divergent enantioselective synthesis of hapalindole-type alkaloids using catalytic asymmetric hydrogenation of a ketone to construct the chiral core structure.

ABSTRACT: A divergent enantioselective approach to hapalindole-type alkaloids is described. The route features a ruthenium-catalyzed asymmetric hydrogenation of a ketone via DKR to construct the chiral trans-1-indolyl-2-isopropenylcyclohexane skeleton and a switchable sequence of methylation and acetylation/aldol reaction to access a chiral quaternary stereocenter. (+)-Hapalindole Q (1, 13 steps, 5.9% overall yield), (-)-12-epi-hapalindole Q isonitrile (2, 15 steps, 5.5% overall yield), (-)-hapalindole D (3, 14 steps, 2.3% overall yield), and (+)-12-epi-fischerindole U isothiocyanate (4, 14 steps, 3.0% overall yield) were synthesized in 13-15 steps from a commercially available material to demonstrate the application of this approach.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6016446 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Divergent enantioselective synthesis of hapalindole-type alkaloids using catalytic asymmetric hydrogenation of a ketone to construct the chiral core structure.

Liu Yang Y Cheng Li-Jie LJ Yue Hai-Tao HT Che Wen W Xie Jian-Hua JH Zhou Qi-Lin QL

Chemical science 20160412 7

A divergent enantioselective approach to hapalindole-type alkaloids is described. The route features a ruthenium-catalyzed asymmetric hydrogenation of a ketone via DKR to construct the chiral trans-1-indolyl-2-isopropenylcyclohexane skeleton and a switchable sequence of methylation and acetylation/aldol reaction to access a chiral quaternary stereocenter. (+)-Hapalindole Q (1, 13 steps, 5.9% overall yield), (-)-12-epi-hapalindole Q isonitrile (2, 15 step ...[more]

PMID: 30155122

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