title: Organocatalytic enantioselective Pictet-Spengler approach to biologically relevant 1-benzyl-1,2,3,4-tetrahydroisoquinoline alkaloids.
abstract: A general procedure for the synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines was developed, based on organocatalytic, regio- and enantioselective Pictet-Spengler reactions (86-92% ee) of N-(o-nitrophenylsulfenyl)-2-arylethylamines with arylacetaldehydes. The presence of the o-nitrophenylsulfenyl group, together with the MOM-protection in the catechol part of the tetrahydroisoquinoline ring system, appeared to be a productive combination. To demonstrate the versatility of this approach, 10 biologically and pharmaceutically relevant alkaloids were prepared using (R)-TRIP as the chiral catalyst: (R)-norcoclaurine, (R)-coclaurine, (R)-norreticuline, (R)-reticuline, (R)-trimemetoquinol, (R)-armepavine, (R)-norprotosinomenine, (R)-protosinomenine, (R)-laudanosine, and (R)-5-methoxylaudanosine.
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ruiz-Olalla
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Martien A
authors.initials: MA
authors.lastname: Würdemann
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Wanner
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Steen
authors.initials: S
authors.lastname: Ingemann
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Jan H
authors.initials: JH
authors.lastname: van Maarseveen
authors.affiliation: Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Henk
authors.initials: H
authors.lastname: Hiemstra
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D044182:Benzylisoquinolines / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D005021:Ethylamines / Q000737:chemistry*; D007546:Isoquinolines / Q000737:chemistry*; D015394:Molecular Structure; D055601:Organic Chemistry Phenomena; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000470:Alkaloids; D044182:Benzylisoquinolines; D001688:Biological Products; D005021:Ethylamines; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C002757:norreticuline; C004690:coclaurine; C001522:laudanosine; C064689:armepavine; C012348:higenamine; C003298:reticuline; C084924:1,2,3,4-tetrahydro-1-(phenylmethyl)isoquinoline