Syntheses of 10-oxo, 10a a-hydroxy, and 10b b-hydroxy derivatives of a potent k k-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 10b bhydroxy-4,5-epoxymorphinan, exclusively. A stepwise inversion method of the 10b b-hydroxy group to produce 10a a-hydroxy-4,5-epoxymorphinan was established. By HPLC analyses, 10a a-hydroxy-TRK-820 12 was confirmed to be one of the degradation products in developing formulation of TRK-820.
Syntheses of 10-Oxo, 10α-Hydroxy, and 10β-Hydroxy Derivatives of a Potent κ-Opioid Receptor Agonist, TRK-820. -The title compounds are supposed to be potential degradation products in formulation of TRK-820 as a result of oxidation. The 10-β-hydroxy derivative (II) is derived from 10-oxo-TPK-820 (I) via stereoselective reduction. A stepwise inversion method is applied to produce the 10α-hydroxy compound (VII) from the β-isomer (IV). -(HORIKIRI, H.; HIRANO, N.; TANAKA, Y.; OISHI, J.; HATAKEYAMA, H.; KAWAMURA*, K.; NAGASE, H.; Chem. Pharm. Bull. 52 (2004) 6, 664-669; Pharm. Res. Lab., Toray Ind., Inc., Kanagawa 248, Japan; Eng.) -M. Paetzel 46-200
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