Syntheses of 10-oxo, 10 alpha-hydroxy, and 10 beta-hydroxy derivatives of a potent kappa-opioid receptor agonist, TRK-820.
Syntheses of 10-oxo, 10alpha-hydroxy, and 10beta-hydroxy derivatives of a potent kappa-opioid receptor selective agonist, TRK-820, are described. These derivatives were supposed to be potential degradation products in formulation of TRK-820 as a result of autoxidation. 10-Oxo-TRK-820 11 was derived from 10-oxo-4,5-epoxymorphinan 14 in 10 steps in 32% overall yield. Reduction of the 10-oxo group in 4,5-epoxymorphinan with NaBH(4) gave 10beta-hydroxy-4,5-epoxymorphinan, exclusively. A stepwise inversion method of the 10beta-hydroxy group to produce 10alpha-hydroxy-4,5-epoxymorphinan was established. By HPLC analyses, 10alpha-hydroxy-TRK-820 12 was confirmed to be one of the degradation products in developing formulation of TRK-820.
Horikiri
Hiromasa
H
Pharmaceutical Research Laboratories, Toray Industries Inc., 1111 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
Hirano
Noriyuki
N
Tanaka
Yoichiro
Y
Oishi
Junji
J
Hatakeyama
Hitoshi
H
Kawamura
Kuniaki
K
Nagase
Hiroshi
H
D009019:Morphinans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D009019:Morphinans; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820