title: Total Synthesis of (-)-Salvinorin A.
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.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 100 W. 18th Ave., Columbus, OH, 43210, USA.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Line
authors.affiliation: Dart NeuroScience LLC, 12278 Scripps Summit Dr., San Diego, CA, 92131, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Burns
authors.affiliation: Department of Chemistry and Biochemistry, The University of Texas at Tyler, 3900 University Blvd., Tyler, TX, 75799, USA.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Butler
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 100 W. 18th Ave., Columbus, OH, 43210, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Casbohm
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, 100 W. 18th Ave., Columbus, OH, 43210, USA.
authors.forename: Craig J
authors.identifier: http://orcid.org/0000-0003-0836-8187
authors.initials: CJ
authors.lastname: Forsyth
mesh_terms: D061565:Cycloaddition Reaction; D045785:Diterpenes, Clerodane / Q000138:chemical synthesis* / Q000737:chemistry; D005663:Furans / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D011807:Quinolizines / Q000737:chemistry*; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000737:chemistry*; D014025:Titanium / Q000737:chemistry*
chemical_list: D045785:Diterpenes, Clerodane; D005663:Furans; D008024:Ligands; D009281:Naphthalenes; D011807:Quinolizines; D013457:Sulfur Compounds; C438055:dithiane; C007229:decalin; D014025:Titanium; C090499:salvinorin A; C039281:furan
keywords: Diels-Alder reaction; natural products; neurochemistry; synthetic methods; xenobiotics