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Formal Total Synthesis of Salvinorin A

Marc Halang, Martin E. Maier

ChemistryOpen October 26, 2022 DOI: 10.1002/open.202200015 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Peer reviewed
Topics Salvia divinorum
Keywords Cyanohydrin Decalins Johnson-claisen rearrangement Wieland-miescher ketone
Key points The Johnson-Claisen rearrangement of an allyl alcohol derived from a Wieland-Miescher ketone produced two diastereomeric 1,4-unsaturated esters in a ratio of approximately 2.6:1, and the major isomer was converted to a key intermediate of the Hagiwara synthesis of salvinorin A.

Abstract

Abstract The generation of the quaternary stereocenter at the C9 position of salvinorin A precursors by the Claisen rearrangement was investigated. The required allyl alcohol was prepared from a Wieland‐Miescher ketone using a known γ‐hydroxylation, reduction of the enone double bond, cyanohydrin formation, and elimination, yielding an unsaturated nitrile. A two‐step reduction led to the required allyl alcohol. The subsequent Johnson‐Claisen rearrangement provided a mixture of two diastereomeric 1,4‐unsaturated esters in a ratio of around 2.6 : 1. The major isomer could be converted to a key intermediate of the Hagiwara synthesis of salvinorin A.

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