title: Formal Synthesis of Sarain A: Intramolecular Cycloaddition of an Eight-Membered Cyclic Nitrone to Construct the 2-Azabicyclo[3.3.1]nonane Framework.
abstract: An enantioselective route to the tetracyclic skeleton of sarain A has been developed. Asymmetric reduction of an ynone introduced a chiral center which was transferred to the contiguous tertiary stereogenic centers through an Ireland-Claisen rearrangement. The 2-azabicyclo[3.3.1]nonane framework was constructed by an unprecedented intramolecular cycloaddition of an eight-membered cyclic nitrone. Using the steric bias of the bicyclic system, the quaternary carbon atom was constructed by a stereoselective aldol reaction. Further ring formations were performed by ring-closing metathesis for the 13-membered ring and an iodoamidation reaction for the pyrrolidine ring. The present synthesis has successfully provided an alternative route to the late-stage intermediate of Overman's synthesis.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan).|Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Takuya
authors.initials: T
authors.lastname: Higo
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan).
authors.forename: Tomoya
authors.initials: T
authors.lastname: Ukegawa
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan). yokosima@ps.nagoya-u.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yokoshima
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601 (Japan). fukuyama@ps.nagoya-u.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Fukuyama
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis*; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis*; D003500:Cyclization; D061565:Cycloaddition Reaction; D009589:Nitrogen Oxides / Q000138:chemical synthesis / Q000737:chemistry*; D011161:Porifera / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000473:Alkanes; D053961:Azabicyclo Compounds; D001688:Biological Products; D001952:Bridged-Ring Compounds; D009589:Nitrogen Oxides; C015388:nitrones; C410431:sarain A; C017573:nonane
keywords: alkaloids; cycloaddition; heterocycles; metathesis; natural products