title: Total synthesis of the tetracyclic antimalarial alkaloid (±)-myrioneurinol.
abstract: The first total synthesis of the tetracyclic antimalarial Myrioneuron alkaloid (±)-myrioneurinol has been accomplished using three highly diastereoselective reactions as pivotal steps: 1) an intramolecular Michael addition of a benzyloxycarbonyl-protected lactam titanium enolate to an α,β-unsaturated ester for construction of the spirocyclic C5 quaternary center and the a/d rings, 2) a malonate anion conjugate addition to a transient nitrosoalkene to install the requisite functionality and configuration at the C7 position, and 3) an intramolecular sulfonyliminium aza-Sakurai reaction to form the b ring and the attendant C9/C10 configuration of the natural product.
authors.affiliation: Department of Chemistry, The Pennsylvania State University, University Park, PA 16802 (USA).
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Nocket
authors.forename: Steven M
authors.initials: SM
authors.lastname: Weinreb
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
chemical_list: D000470:Alkaloids; D000962:Antimalarials; D001688:Biological Products; D006576:Heterocyclic Compounds, 4 or More Rings; C000599982:myrioneurinol
keywords: Michael addition; alkaloids; natural products; nitrogen heterocycles; total synthesis