title: Total Synthesis of (-)-Morphine.
abstract: Asymmetric total synthesis of (-)-morphine has been accomplished in 18 steps from commercially available 7-methoxy-2-tetralone. Our synthesis features a simple transformation from a readily prepared chiral intermediate, construction of the E-ring by acid-mediated cyclization, and singlet oxygen-mediated manipulation of the C-ring. Transformation of the final stage involves construction of the morphinan skeleton by means of 1,6-addition of in situ generated secondary amine.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Hirotatsu
authors.initials: H
authors.lastname: Umihara
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi, 464-8601, Japan.
authors.forename: Satoshi
authors.identifier: http://orcid.org/0000-0003-4036-0062
authors.initials: S
authors.lastname: Yokoshima
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
authors.forename: Masayuki
authors.identifier: http://orcid.org/0000-0003-3274-551X
authors.initials: M
authors.lastname: Inoue
authors.affiliation: Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya, Aichi, 464-8601, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Fukuyama
mesh_terms: D003500:Cyclization; D009020:Morphine / Q000138:chemical synthesis* / Q000737:chemistry; D026082:Singlet Oxygen / Q000737:chemistry; D013237:Stereoisomerism; D044024:Tetralones / Q000737:chemistry
chemical_list: C570728:7-methoxy-2-tetralone; D044024:Tetralones; D026082:Singlet Oxygen; D009020:Morphine
keywords: aldol reaction; conjugate addition; morphine; singlet oxygen; total synthesis