title: A second generation formal synthesis of (-)-cephalotaxine.
abstract: A second generation formal synthesis of the alkaloid (-)-cephalotaxine has been achieved using an alkylidene carbene 1,5-CH insertion reaction to establish a key quaternary stereocenter. The carbene precursor was readily derived from L-proline, and the 1,5-CH insertion reaction was performed under Ohira's conditions using lithiotrimethylsilyldiazomethane (LTDM), which gave the desired spirocyclic product in 74% yield. The hydroxymethyl group was then oxidized and then decarbonylated (93%), and this material was easily transformed into the desired Friedel-Crafts cyclization precursor. Exposure of this material to SnCl4 then gave the desired pentacyclic product, which was identical to that previously prepared by Mori and thus represents a formal total synthesis of (-)-cephalotaxine.
authors.affiliation: The School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Abdul
authors.initials: A
authors.lastname: Hameed
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Blake
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hayes
mesh_terms: D003978:Diazomethane / Q000031:analogs & derivatives / Q000737:chemistry; D006248:Harringtonines / Q000138:chemical synthesis*; D000077863:Homoharringtonine; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D013237:Stereoisomerism; D017971:Tin Compounds / Q000737:chemistry; D014297:Trimethylsilyl Compounds / Q000737:chemistry
chemical_list: C451480:(trimethylsilyl)diazaomethane; D006248:Harringtonines; D017971:Tin Compounds; D014297:Trimethylsilyl Compounds; C030011:carbene; D003978:Diazomethane; C041694:stannic chloride; D000077863:Homoharringtonine; D011392:Proline; D008697:Methane