title: Saludimerines A and B, novel-type dimeric alkaloids with stereogenic centers and configurationally semistable biaryl axes.
abstract: The first biarylic bis-morphinanedienone alkaloids, saludimerines A (3a) and B (3b), isolated from a tree of Croton flavens (Euphorbiaceae) are described. These naturally occurring dimers of the known alkaloid salutaridine are joined together via a rotationally hindered biaryl axis, giving rise to atropo-diastereomers that are configurationally stable at room temperature but slowly interconvert in methanolic solution within several days. Their structures were established by spectroscopic methods and by partial synthesis, which was achieved by a highly atropo-diastereoselective biomimetic oxidative coupling of the monomeric precursor, salutaridine. Their axial configurations were elucidated by circular dichroism (CD) investigations, which succeeded despite the fact that the two atropo-diastereomers exhibit near-identical CD spectra. This remarkable phenomenon was rationalized by quantum chemical CD calculations. The configurational assignment of saludimerines A (3a) as P-axial and B (3b) as M was corroborated by atropisomer-specific NOE interactions between protons of the one molecular half with nuclei in the other.
authors.affiliation: Department Pharmazie, Ludwig-Maximilians-Universität, Butenandtstrasse 5-13, D-81377 Münich, Germany. franz.bracher@cup.uni-muenchen.de
authors.forename: Franz
authors.initials: F
authors.lastname: Bracher
authors.forename: Wolfram J
authors.initials: WJ
authors.lastname: Eisenreich
authors.forename: Jörg
authors.initials: J
authors.lastname: Mühlbacher
authors.forename: Michael
authors.initials: M
authors.lastname: Dreyer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bringmann
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D002942:Circular Dichroism / Q000379:methods; D018360:Crystallography, X-Ray; D019281:Dimerization; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009022:Morphine Derivatives / Q000737:chemistry* / Q000302:isolation & purification; D018515:Plant Leaves / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D009022:Morphine Derivatives; C495895:saludimerine A; C495897:saludimerine B