title: Enantioselective Synthesis and Racemization of (-)-Sinoracutine.
abstract: Sinoracutine is a recently isolated alkaloid with unusual stereochemical and biological properties. It features an unprecedented tetracyclic 6/6/5/5 skeleton that bears an N-methylpyrrolidine ring fused to a cyclopentenone. Interestingly, both enantiomers of sinoracutine have been independently isolated from the same plant, yet the molecule does not appear to occur as a racemate. Here, we present a short synthesis of (-)-sinoracutine that relies on a highly diastereoselective Pauson-Khand reaction and a Mandai-Claisen reaction to install the quaternary stereocenter. Our work establishes the absolute configuration of the levorotatory isomer and suggests that the optical purity of sinoracutine varies in nature due to its gradual racemization. Experimental evidence supports this proposal, and a plausible mechanism for the racemization is provided.
authors.affiliation: Department of Chemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.
authors.forename: Giulio
authors.initials: G
authors.lastname: Volpin
authors.affiliation: Department of Chemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.
authors.forename: Nynke A
authors.initials: NA
authors.lastname: Vepřek
authors.affiliation: Department of Chemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.
authors.forename: Andreas B
authors.initials: AB
authors.lastname: Bellan
authors.affiliation: Department of Chemistry, Ludwig-Maximilians-Universität München, 81377, Munich, Germany.
authors.forename: Dirk
authors.identifier: 0000-0002-6782-6056
authors.initials: D
authors.lastname: Trauner
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D003517:Cyclopentanes; D011759:Pyrrolidines; C000628624:sinoracutine
keywords: Kornblum oxidation; Pauson-Khand reaction; alkaloids; asymmetric synthesis; sigmatropic rearrangement