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Total Synthesis of Dapholdhamine B and Dapholdhamine B Lactone.

Total Synthesis of Dapholdhamine B and Dapholdhamine B Lactone. The intriguing structural complexity and bioactivities of the Daphniphyllum alkaloids have long attracted much attention. Herein, we report the first and enantioselective total synthesis of Daphniphyllum alkaloid dapholdhamine B and its lactone derivative. The chemical structure of dapholdhamine B contains a unique aza-adamantane core skeleton and eight contiguous stereocenters, including three contiguous fully substituted stereocenters, which present a formidable synthetic challenge. This concise approach used to achieve the first synthesis of an aza-adamantane natural product features a vinylogous Mannich reaction, an optimized α-bromo-α,β-unsaturated ketone synthesis, a substrate-dependent intramolecular aza-Michael addition, a key annulation via amide activation, an SN2'-type lactonization, and a facile Horner-Wadsworth-Emmons reaction that converts the hemiacetal moiety to the corresponding homologated carboxylic acid. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of the American Chemical Society Pubmed

Total Synthesis of Dapholdhamine B and Dapholdhamine B Lactone.

Journal of the American Chemical Society , Volume 141 (29): 8 – Nov 9, 2020

Total Synthesis of Dapholdhamine B and Dapholdhamine B Lactone.


Abstract

The intriguing structural complexity and bioactivities of the Daphniphyllum alkaloids have long attracted much attention. Herein, we report the first and enantioselective total synthesis of Daphniphyllum alkaloid dapholdhamine B and its lactone derivative. The chemical structure of dapholdhamine B contains a unique aza-adamantane core skeleton and eight contiguous stereocenters, including three contiguous fully substituted stereocenters, which present a formidable synthetic challenge. This concise approach used to achieve the first synthesis of an aza-adamantane natural product features a vinylogous Mannich reaction, an optimized α-bromo-α,β-unsaturated ketone synthesis, a substrate-dependent intramolecular aza-Michael addition, a key annulation via amide activation, an SN2'-type lactonization, and a facile Horner-Wadsworth-Emmons reaction that converts the hemiacetal moiety to the corresponding homologated carboxylic acid.

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References (83)

ISSN
0002-7863
eISSN
1520-5126
DOI
10.1021/jacs.9b05641
pmid
31299155

Abstract

The intriguing structural complexity and bioactivities of the Daphniphyllum alkaloids have long attracted much attention. Herein, we report the first and enantioselective total synthesis of Daphniphyllum alkaloid dapholdhamine B and its lactone derivative. The chemical structure of dapholdhamine B contains a unique aza-adamantane core skeleton and eight contiguous stereocenters, including three contiguous fully substituted stereocenters, which present a formidable synthetic challenge. This concise approach used to achieve the first synthesis of an aza-adamantane natural product features a vinylogous Mannich reaction, an optimized α-bromo-α,β-unsaturated ketone synthesis, a substrate-dependent intramolecular aza-Michael addition, a key annulation via amide activation, an SN2'-type lactonization, and a facile Horner-Wadsworth-Emmons reaction that converts the hemiacetal moiety to the corresponding homologated carboxylic acid.

Journal

Journal of the American Chemical SocietyPubmed

Published: Nov 9, 2020

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