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Total Synthesis of (-)-Salvinorin A.

Nathan J Line, Aaron C Burns, Sean C Butler, Jerry Casbohm, Craig J Forsyth

Chemistry (Weinheim an der Bergstrasse, Germany) December 12, 2016 DOI: 10.1002/chem.201604853 (opens in new tab)

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AI-extracted from the abstract
Characteristics Theoretical or philosophical paper Peer reviewed
Topics Salvia divinorum
Keywords Diels-alder reaction Natural products Neurochemistry Synthetic methods Xenobiotics Organic synthesis Chemical synthesis Total synthesis Reaction methodology Chemical reactions Bioactive compounds Plant compounds Brain receptors Brain science Pharmacology Chemical biology Drug action
Citations 41
Key points Describes a total synthesis of salvinorin A that uses l-(+)-tartaric acid stereochemistry and an unprecedented allylic dithiane intramolecular Diels-Alder reaction.

Abstract

Salvinorin A (1) is natural hallucinogen that binds the human κ-opioid receptor. A total synthesis has been developed that parlays the stereochemistry of l-(+)-tartaric acid into that of (-)-1 via an unprecedented allylic dithiane intramolecular Diels-Alder reaction to obtain the trans-decalin scaffold. Tsuji allylation set the C9 quaternary center and a late-stage stereoselective chiral ligand-assisted addition of a 3-titanium furan upon a C12 aldehyde/C17 methyl ester established the furanyl lactone moiety. The tartrate diol was finally converted into the C1,C2 keto-acetate.

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