title: Stereocontrolled enantioselective total synthesis of the [2+2] quadrigemine alkaloids.
abstract: A unified strategy for enantioselective total synthesis of all stereoisomers of the 2+2 family of quadrigemine alkaloids is reported. In this approach, two enantioselective intramolecular Heck reactions are carried out at the same time on precursors fashioned in four steps from eithermeso- or (+)-chimonanthine to form the two critical quaternary carbons of the peripheral cyclotryptamine rings of these products. Useful levels of catalyst control are realized in either desymmetrizing amesoprecursor or controlling diastereoselectivity in elaboratingC2-symmetic intermediates. None of the synthetic quadrigemines are identical with alkaloids isolated previously and referred to as quadrigemines A and E. In addition, we report improvements in our previous total syntheses of (+)- or (-)-quadrigemine C that shortened the synthetic sequence to 10 steps and provided these products in 2.2% overall yield from tryptamine.
authors.affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Canham
authors.affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025 ; City Hope Comprehensive Cancer Center, Beckman Research Institute, Department of Molecular Medicine, 1500 E. Duarte Road, Duarte, California 91010.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Hafensteiner
authors.affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025.
authors.forename: Alec D
authors.initials: AD
authors.lastname: Lebsack
authors.affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025.
authors.forename: Tricia L
authors.initials: TL
authors.lastname: May-Dracka
authors.affiliation: City Hope Comprehensive Cancer Center, Beckman Research Institute, Department of Molecular Medicine, 1500 E. Duarte Road, Duarte, California 91010.
authors.forename: Sangkil
authors.initials: S
authors.lastname: Nam
authors.affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Stearns
authors.affiliation: Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025.
authors.forename: Larry E
authors.initials: LE
authors.lastname: Overman
keywords: Stereocontrolled total synthesis; alkaloid; enantioselective catalysis; intramolecular Heck reaction