Enantioselective Oxidative Aerobic Dealkylation of N-Ethyl Benzylisoquinolines by Employing the Berberine Bridge Enzyme.
N-Dealkylation methods are well described for organic chemistry and the reaction is known in nature and drug metabolism; however, to our knowledge, enantioselective N-dealkylation has not been yet reported. In this study, exclusively the (S)-enantiomers of racemic N-ethyl tertiary amines (1-benzyl-N-ethyl-1,2,3,4-tetrahydroisoquinolines) were dealkylated to give the corresponding secondary (S)-amines in an enantioselective fashion at the expense of molecular oxygen. The reaction is catalyzed by the berberine bridge enzyme, which is known for CC bond formation. The dealkylation was demonstrated on a 100 mg scale and gave optically pure dealkylated products (ee>99 %).
Institut für Chemie, Organische & Bioorganische Chemie, Universität Graz, NAWI Graz, Heinrichstraße 28, 8010 Graz (Austria).|Department of Pure Chemistry, Faculty of Chemistry, Shahid Beheshti University, G.C. District 1, Evin, Daneshjou Blvd, Tehran (Iran).
Somayyeh
S
Gandomkar
Institut für Chemie, Organische & Bioorganische Chemie, Universität Graz, NAWI Graz, Heinrichstraße 28, 8010 Graz (Austria).
Eva-Maria
EM
Fischereder
Institut für Chemie, Organische & Bioorganische Chemie, Universität Graz, NAWI Graz, Heinrichstraße 28, 8010 Graz (Austria).
Joerg H
JH
Schrittwieser
Institut für Biochemie, Technische Universität Graz, Petersgasse 12, 8010 Graz (Austria).
Silvia
S
Wallner
Department of Pure Chemistry, Faculty of Chemistry, Shahid Beheshti University, G.C. District 1, Evin, Daneshjou Blvd, Tehran (Iran).
Zohreh
Z
Habibi
Institut für Biochemie, Technische Universität Graz, Petersgasse 12, 8010 Graz (Austria).
Peter
P
Macheroux
Institut für Chemie, Organische & Bioorganische Chemie, Universität Graz, NAWI Graz, Heinrichstraße 28, 8010 Graz (Austria).
Wolfgang
W
Kroutil
D000478:Alkylation; D000588:Amines / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D031675:Eschscholzia / Q000201:enzymology; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000737:chemistry / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
D000588:Amines; D007546:Isoquinolines; C071690:reticuline oxidase; D010089:Oxidoreductases, N-Demethylating; D010100:Oxygen
N-dealkylation; alkaloids; asymmetric synthesis; enantioselective; enzyme catalysis