Total synthesis of enigmazole A from Cinachyrella enigmatica. Bidirectional bond constructions with an ambident 2,4-disubstituted oxazole synthon
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Updated: Jun 11, 2026
![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Colin K Skepper1, Tim Quach, Tadeusz F Molinski
1Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive MC0358, La Jolla, California 92093, USA.
Abstract:
The first total synthesis of the cytotoxic marine macrolide enigmazole A has been completed in 22 steps (longest linear sequence). The sensitive, densely functionalized 2,4-disubstituted oxazole fragment was constructed using an efficient Negishi-type coupling of an oxazol-2-ylzinc reagent formed directly from the parent ethyl 2-iodooxazole-4-carboxylate by zinc insertion. Other key steps include a hetero-Diels-Alder cycloaddition to form the central embedded pyran ring, a Wittig reaction to unite Eastern and Western hemispheres, and a ring size-selective Keck macrolactonization.
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