title: The first example of the stereoselective synthesis of 7 beta-carbamoyl-4,5alpha-epoxymorphinan via a novel and reactive gamma-lactone.
abstract: 7beta-Carbamoyl-4,5alpha-epoxymorphinans 5 were stereoselectively synthesized from the 7alpha-carboxylate intermediate 3 in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and amines under reflux conditions in mesitylene via a novel and reactive gamma-lactone 7. These were the first examples of the stereoselective syntheses of 7beta-substituted 4,5alpha-epoxymorphinans. The mechanism of the reaction process was elucidated as follows: 1) epimerization of 7alpha-carboxylate 3, 2) intramolecular lactonization of 7beta-carboxylate 6, and 3) aminolysis of the resultant gamma-lactone 7. The aminolysis of the isolated reactive gamma-lactone 7 with allylamine and the alcoholysis with MeOH in the presence of NaBH(4) proceeded at room temperature. The gamma-lactone 7 can be a useful intermediate for the preparation of 7beta-substituted 4,5alpha-epoxymorphinans that would be potent selective delta opioid receptor ligands. The stereoselective syntheses of the 7alpha-carbamoyl-4,5alpha-epoxymorphinans 9 from 7alpha-carboxylate 3 via 7alpha-carboxylic acid were also successful.
authors.affiliation: Pharmaceutical Research Laboratories, Toray Industries Inc., 1111 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Fujii
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hirano
authors.forename: Hiromi
authors.initials: H
authors.lastname: Uchiro
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Kawamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagase
mesh_terms: D007783:Lactones / Q000138:chemical synthesis*; D009019:Morphinans / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D007783:Lactones; D009019:Morphinans