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Deconstructive Asymmetric Total Synthesis of Morphine-Family Alkaloid (-)-Thebainone A.

ABSTRACT: Herein, we describe the development of a deconstructive strategy for the first asymmetric synthesis of (-)-thebainone A, capitalizing on an enantioselective C-C bond activation and a C-O bond cleavage reaction. The rhodium-catalyzed asymmetric "cut-and-sew" transformation between sterically hindered trisubstituted alkenes and benzocyclobutenones allowed efficient construction of the fused A/B/C rings and the quaternary center of the natural product. The newly optimized conditions show broad substrate scope and excellent enantioselectivity (up to 99.5:0.5 er). Taking advantage of boron-mediated ether bond cleavage, we completed the synthesis of the morphine alkaloid (-)-thebainone A by two complementary routes.

SUBMITTER: Hou SH

PROVIDER: S-EPMC8159902 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Deconstructive Asymmetric Total Synthesis of Morphine-Family Alkaloid (-)-Thebainone A.

Hou Si-Hua SH Prichina Adriana Y AY Dong Guangbin G

Angewandte Chemie (International ed. in English) 20210502 23

Herein, we describe the development of a deconstructive strategy for the first asymmetric synthesis of (-)-thebainone A, capitalizing on an enantioselective C-C bond activation and a C-O bond cleavage reaction. The rhodium-catalyzed asymmetric "cut-and-sew" transformation between sterically hindered trisubstituted alkenes and benzocyclobutenones allowed efficient construction of the fused A/B/C rings and the quaternary center of the natural product. The newly optimized conditions show broad subs ...[more]

PMID: 33822455

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