title: A unified approach to ent-atisane diterpenes and related alkaloids: synthesis of (-)-methyl atisenoate, (-)-isoatisine, and the hetidine skeleton.
abstract: A unified approach to ent-atisane diterpenes and related atisine and hetidine alkaloids has been developed from ent-kaurane (-)-steviol (1). The conversion of the ent-kaurane skeleton to the ent-atisane skeleton features a Mukaiyama peroxygenation with concomitant cleavage of the C13-C16 bond. Conversion to the atisine skeleton (9) features a C20-selective C-H activation using a Suárez modification of the Hofmann-Löffler-Freytag (HLF) reaction. A cascade sequence involving azomethine ylide isomerization followed by Mannich cyclization forms the C14-C20 bond in the hetidine skeleton (8). Finally, attempts to form the N-C6 bond of the hetisine skeleton (7) with a late-stage HLF reaction are discussed. The synthesis of these skeletons has enabled the completion of (-)-methyl atisenoate (3) and (-)-isoatisine (4).
authors.affiliation: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Cherney
authors.forename: Justin M
authors.initials: JM
authors.lastname: Lopchuk
authors.forename: Jason C
authors.initials: JC
authors.lastname: Green
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D045786:Diterpenes, Kaurane / Q000737:chemistry*; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000470:Alkaloids; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D010080:Oxazoles