A Synthesis of Alstonlarsine A via Alstolucines B and F Demonstrates the Chemical Feasibility of a Proposed Biogenesis

We offer a new biogenetic proposal for the origin of the complex alkaloid alstonlarsine A, through rearrangement of the Strychnos alkaloids alstolucines B and F. Further, we provide evidence of the chemical feasibility of this proposal in the facile conversion of synthetic alstolucines into alstonla...

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Bibliographic Details
Published inAngewandte Chemie Vol. 135; no. 4
Main Authors Barnes, Griffin L., Hong, Allen Y., Vanderwal, Christopher D.
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 23.01.2023
Subjects
Alkaloids
Biosynthesis
Chemistry
Feasibility
Hydrides
Internal Redox
Mannich Reaction
Methylation
Total Synthesis
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Summary:We offer a new biogenetic proposal for the origin of the complex alkaloid alstonlarsine A, through rearrangement of the Strychnos alkaloids alstolucines B and F. Further, we provide evidence of the chemical feasibility of this proposal in the facile conversion of synthetic alstolucines into alstonlarsine A through a short, efficient sequence of N‐methylation, β‐elimination, and a cascade 1,7‐hydride shift/Mannich cyclization. We believe that this is the first biogenetic proposal involving the “tert‐amino effect”, a hydride‐shift‐based internal redox trigger of a Mannich cyclization. A further interesting feature of the cascade is that its stereochemical outcome most likely originates in conformational preferences during the hydride shift. Alstonlarsine A, an indole monoterpene alkaloid isolated from Alstonia plants, was prepared by a rearrangement of other Alstonia alkaloids, alstolucines B and F. The successful process was patterned after a revised biogenetic proposal that features the first example of the “tert‐amino effect” in alkaloid biogenesis.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202215098