title: Biocatalytic organic synthesis of optically pure (S)-scoulerine and berbine and benzylisoquinoline alkaloids.
abstract: A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C-C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4-8 linear steps using either a Bischler-Napieralski cyclization or a C1-Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5-9 linear steps.
authors: Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, 8010 Graz, Austria.
authors: Joerg H
authors: JH
authors: Schrittwieser
authors: Verena
authors: V
authors: Resch
authors: Silvia
authors: S
authors: Wallner
authors: Wolf-Dieter
authors: WD
authors: Lienhart
authors: Johann H
authors: JH
authors: Sattler
authors: Jasmin
authors: J
authors: Resch
authors: Peter
authors: P
authors: Macheroux
authors: Wolfgang
authors: W
authors: Kroutil
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D044182:Benzylisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D001600:Berberine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D055162:Biocatalysis; D003500:Cyclization; D015394:Molecular Structure; D055601:Organic Chemistry Phenomena; D010084:Oxidation-Reduction; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D044182:Benzylisoquinolines; D001600:Berberine Alkaloids; C010941:discretamine; C014845:berbine