title: Fischer Indolizations as a Strategic Platform for the Total Synthesis of Picrinine.
abstract: Picrinine, which is a member of the akuammiline family of alkaloids, was first isolated in 1965 from the leaves of Alstonia scholaris. The natural product possesses a daunting polycyclic skeleton that contains a furanoindoline, a bridged [3.3.1]azabicycle, two N,O-acetal linkages, and six stereogenic centers. These structural features render picrinine a challenging and attractive target for total synthesis. This paper provides a full account of our synthetic forays toward picrinine, which culminates in the first total synthesis of this long-standing target. Central to the success of our approach is the use of the Fischer indolization reaction to introduce the C7 quaternary stereocenter and the indoline nucleus of the natural product's scaffold. We probe some of the subtleties of this classic transformation by examining some of the most complex Fischer indolization substrates to date. Additionally, we describe various roadblocks encountered in our experimental efforts, which were successfully overcome to complete the total synthesis of picrinine.
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Smith
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Jesus
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Ben W
authors.initials: BW
authors.lastname: Boal
authors.affiliation: Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
authors.forename: Neil K
authors.initials: NK
authors.lastname: Garg
mesh_terms: D000470:Alkaloids / Q000737:chemistry; D031051:Alstonia / Q000737:chemistry*; D053961:Azabicyclo Compounds / Q000737:chemistry*; D001688:Biological Products; D026121:Indole Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000470:Alkaloids; D053961:Azabicyclo Compounds; D001688:Biological Products; D026121:Indole Alkaloids; D007211:Indoles; C528220:picrinine; C057812:indoline