Syntheses of 10-oxo, 10α-hydroxy, and 10β-hydroxy derivatives of a potent κ-opioid receptor agonist, TRK-820

被引：9

作者：

Horikiri, H ^{[1
]}

Hirano, N ^{[1
]}

Tanaka, Y ^{[1
]}

Oishi, J ^{[1
]}

Hatakeyama, H ^{[1
]}

Kawamura, K ^{[1
]}

Nagase, H ^{[1
]}

机构：

[1] Toray Industries Ltd, Pharmaceut Res Labs, Kamakura, Kanagawa 2488555, Japan

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 2004年 / 52卷 / 06期

关键词：

TRK-820; degradation product; 10-oxo-4,5-epoxymorphinan; 10-oxo-TRK-820; 10; alpha-hydroxy-TRK-820; beta-hydroxy-TRK-820;

D O I：

10.1248/cpb.52.664

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 NaBH4 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.

引用

页码：664 / 669

页数：6

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