The First Example of the Stereoselective Synthesis of 7.BETA.-Carbamoyl-4,5.ALPHA.-epoxymorphinan via a Novel and Reactive .GAMMA.-Lactone
In: Chemical and Pharmaceutical Bulletin, Jg. 52 (2004), S. 747-750
Online
unknown
Zugriff:
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.
Titel: |
The First Example of the Stereoselective Synthesis of 7.BETA.-Carbamoyl-4,5.ALPHA.-epoxymorphinan via a Novel and Reactive .GAMMA.-Lactone
|
---|---|
Autor/in / Beteiligte Person: | Nagase, Hiroshi ; Hirano, Noriyuki ; Uchiro, Hiromi ; Kawamura, Kuniaki ; Fujii, Hideaki |
Link: | |
Zeitschrift: | Chemical and Pharmaceutical Bulletin, Jg. 52 (2004), S. 747-750 |
Veröffentlichung: | Pharmaceutical Society of Japan, 2004 |
Medientyp: | unknown |
ISSN: | 1347-5223 (print) ; 0009-2363 (print) |
DOI: | 10.1248/cpb.52.747 |
Schlagwort: |
|
Sonstiges: |
|