title: Progress toward the syntheses of (+)-GB 13, (+)-himgaline, and himandridine. new insights into intramolecular imine/enamine aldol cyclizations.
abstract: A full account of our total synthesis of the galbulimima alkaloids GB 13 and himgaline is provided. Using a strategy adapted from the proposed biosynthesis of the GB alkaloid family, a linear precursor underwent successive intramolecular Diels-Alder, Michael, and imine aldol cyclizations to form the polycyclic alkaloid core. We now show that modification of this strategy can also deliver an advanced intermediate en route to the related alkaloid himandridine. The success of the key imine aldol cyclization is acutely sensitive to substrate structure and solvent, including a case in which cyclization was spontaneous in protic solvents. A detailed computational investigation of the course of the reaction closely correlates with, and suggests a rationale for, the observed patterns of imine aldol reactivity.
authors.affiliation: Department of Chemistry & Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, United States. evans@chemistry.harvard.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Evans
authors.forename: Drew J
authors.initials: DJ
authors.lastname: Adams
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Kwan
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D013379:Substrate Specificity; D013696:Temperature
chemical_list: D000470:Alkaloids; C518378:Galbulimima alkaloid 13; D006571:Heterocyclic Compounds; D006576:Heterocyclic Compounds, 4 or More Rings; D007097:Imines; C518376:himgaline; C487223:himandrine