Synthesis of Strophasterol A Guided by a Proposed Biosynthesis and Innate Reactivity

The synthesis of strophasterol A, a moderator of endoplasmatic reticulum (ER) stress in Alzheimer's disease, and the first member of a structurally unprecedented class of secosterols, was achieved through the implementation of a key step of its proposed biosynthesis and two C−H oxidations. Analysis of the innate reactivity of the intermediates enabled the identification of a novel way to prepare an α‐chloro‐γ‐hydroxy‐δ‐keto enone, as well as its vinylogous α‐ketol rearrangement to a δ‐keto carboxylic acid.