title: Synthesis of ultra-short-acting neuromuscular blocker GW 0430: a remarkably stereo- and regioselective synthesis of mixed tetrahydroisoquinolinium chlorofumarates.
abstract: [formula: see text] The stereo- and regioselective synthesis of ultra-short-acting nondepolarizing neuromuscular blocker GW 0430 (5a) is described. Key steps involved the enantioselective transfer hydrogenation of imine 8 employing Noyori's catalyst, the stereoselective crystallization and methanolysis of trans-bataines 11 and 12, and the stereo- and regioselective trans elimination of hydrogen chloride from 14. The latter transformation allowed complete control of the position of the chloro substituent and stereochemistry at the double bond of the linker in 15.
authors.affiliation: Department of Chemistry, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA. vs43467@glaxowellcome.com
authors.forename: V
authors.initials: V
authors.lastname: Samano
authors.forename: J A
authors.initials: JA
authors.lastname: Ray
authors.forename: J B
authors.initials: JB
authors.lastname: Thompson
authors.forename: R A
authors.initials: RA
authors.lastname: Mook
authors.forename: D K
authors.initials: DK
authors.lastname: Jung
authors.forename: C S
authors.initials: CS
authors.lastname: Koble
authors.forename: M T
authors.initials: MT
authors.lastname: Martin
authors.forename: E C
authors.initials: EC
authors.lastname: Bigham
authors.forename: C S
authors.initials: CS
authors.lastname: Regitz
authors.forename: P L
authors.initials: PL
authors.lastname: Feldman
authors.forename: E E
authors.initials: EE
authors.lastname: Boros
mesh_terms: D003460:Crystallization; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D000432:Methanol; D009466:Neuromuscular Blocking Agents / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: C410428:GW 0430; D007546:Isoquinolines; D009466:Neuromuscular Blocking Agents; D000432:Methanol