title: Asymmetric total synthesis of dendrobatid alkaloids: preparation of indolizidine 251F and its 3-desmethyl analogue using an intramolecular Schmidt reaction strategy.
abstract: Total syntheses of alkaloid 251F (1), a natural product detected from the skin extracts of the dendrobatid frog species Minyobates bombetes, and its racemic 3-desmethyl derivative (2) are reported. A Diels-Alder reaction initiated both syntheses and established four consecutive stereogenic centers. Important to the synthesis of 2 was a first-generation ozonolysis/olefination/aldol strategy to convert a [2.2.1] bicyclic acid to the [3.3.0]bicyclooctane diquinane 4b. Further elaboration to an appropriate keto azide allowed for a key intramolecular Schmidt reaction to deliver the tricyclic core of the target molecule. In a second-generation approach, a tandem ring-opening/ring-closing metathesis reaction effected an overall [2.2.1] --> [3.3.0] skeletal rearrangement to deliver diquinane 4a. In similar fashion, 4a was manipulated to an appropriate keto azide, and an intramolecular Schmidt reaction generated the core cyclic architecture of 251F.
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, Room 4070, Malott Hall, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045-7582, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Wrobleski
authors.forename: Kiran
authors.initials: K
authors.lastname: Sahasrabudhe
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry*; D018360:Crystallography, X-Ray; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D007212:Indolizines; C488519:indolizidine 251F