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Enantioselective total synthesis of the unnatural enantiomer of quinine.

ABSTRACT: A practical enantioselective total synthesis of the unnatural (+)-quinine and (-)-9-epi-quinine enantiomers, which are important organocatalysts, is reported. The key transformation is a successive organocatalytic formal aza [3 + 3] cycloaddition/Strecker-type cyanation reaction to form an optically active tetrasubstituted piperidine derivative. This organocatalytic reaction proceeded in high yield and gave excellent enantiomeric excess with only 0.5 mol% catalyst loading. In addition, an imidate group, derived from a cyano group, was incorporated in the strategy for site-selective modification of the C4-alkyl chiral piperidine ring of quinine. Furthermore, an efficient coupling between the quinuclidine precursor and dihydroquinoline unit was achieved on a gram scale. The 15-step (LLS) synthetic protocol provided both (+)-quinine and (-)-9-epi-quinine, each with 16% overall yield.

SUBMITTER: Shiomi S

PROVIDER: S-EPMC7020653 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Enantioselective total synthesis of the unnatural enantiomer of quinine.

Shiomi Shinya S Misaka Remi R Kaneko Mayu M Ishikawa Hayato H

Chemical science 20190927 41

A practical enantioselective total synthesis of the unnatural (+)-quinine and (-)-9-<i>epi</i>-quinine enantiomers, which are important organocatalysts, is reported. The key transformation is a successive organocatalytic formal aza [3 + 3] cycloaddition/Strecker-type cyanation reaction to form an optically active tetrasubstituted piperidine derivative. This organocatalytic reaction proceeded in high yield and gave excellent enantiomeric excess with only 0.5 mol% catalyst loading. In addition, an ...[more]

PMID: 32110303

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