title: Intermolecular Diels-Alder Cycloaddition for the Construction of Bicyclo[2.2.2]diazaoctane Structures: Formal Synthesis of Brevianamide B and Premalbrancheamide.
abstract: A stereoselective intermolecular Diels-Alder cycloaddition of an intermediate pyrazinone with both achiral and chiral acrylate-derived dienophiles provides rapid access to the bicyclo[2.2.2]diazaoctane core shared among several prenylated indole alkaloids. The product derived from cycloaddition with 2-nitroacrylate required an additional five to six synthetic operations to intercept established precursors to premalbrancheamide and brevianamide B. The chemistry detailed in this manuscript constitutes a formal total synthesis (12 steps each) of these [2.2.2]diazabicyclic natural products from proline methyl ester.
authors.affiliation: Department of Chemistry, The College of William & Mary , P.O. Box 8795, Williamsburg, Virginia 23187, United States.
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Robins
authors.affiliation: Department of Chemistry, The College of William & Mary , P.O. Box 8795, Williamsburg, Virginia 23187, United States.
authors.forename: Kyu J
authors.initials: KJ
authors.lastname: Kim
authors.affiliation: Department of Chemistry, The College of William & Mary , P.O. Box 8795, Williamsburg, Virginia 23187, United States.
authors.forename: Alex J
authors.initials: AJ
authors.lastname: Chinn
authors.affiliation: Department of Chemistry, The College of William & Mary , P.O. Box 8795, Williamsburg, Virginia 23187, United States.
authors.forename: John S
authors.initials: JS
authors.lastname: Woo
authors.affiliation: Department of Chemistry, The College of William & Mary , P.O. Box 8795, Williamsburg, Virginia 23187, United States.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Scheerer
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D061565:Cycloaddition Reaction; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry*; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D001372:Aza Compounds; D001688:Biological Products; D001643:Bridged Bicyclo Compounds; D010879:Piperazines; D013141:Spiro Compounds; C000611147:bicyclo(2.2.2)diazaoctane; D011392:Proline; C116214:brevianamide B