Total synthesis of lissodendoric acid A via stereospecific trapping of a strained cyclic allene

Small rings that contain allenes are unconventional transient compounds that have been known since the 1960s. Despite being discovered around the same time as benzyne and offering a number of synthetically advantageous features, strained cyclic allenes have seen relatively little use in chemical syn...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2023-01, Vol.379 (6629), p.261-265
Main Authors: Ippoliti, Francesca M, Adamson, Nathan J, Wonilowicz, Laura G, Nasrallah, Daniel J, Darzi, Evan R, Donaldson, Joyann S, Garg, Neil K
Format: Article
Language:English
Subjects:
Allene
Bonding strength
Chemical synthesis
Chemists
Cycloaddition
Diels-Alder reactions
Fluorides
Intermediates
Natural products
Reagents
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Summary:Small rings that contain allenes are unconventional transient compounds that have been known since the 1960s. Despite being discovered around the same time as benzyne and offering a number of synthetically advantageous features, strained cyclic allenes have seen relatively little use in chemical synthesis. We report a concise total synthesis of the manzamine alkaloid lissodendoric acid A, which hinges on the development of a regioselective, diastereoselective, and stereospecific trapping of a fleeting cyclic allene intermediate. This key step swiftly assembles the azadecalin framework of the natural product, allows for a succinct synthetic endgame, and enables a 12-step total synthesis (longest linear sequence; 0.8% overall yield). These studies demonstrate that strained cyclic allenes are versatile building blocks in chemical synthesis.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.ade0032