Syntheses of 10-Oxo, 10α-Hydroxy, and 10β-Hydroxy Derivatives of a Potent κ-Opioid Receptor Agonist, TRK-820

抄録

Syntheses of 10-oxo, 10α-hydroxy, and 10β-hydroxy derivatives of a potent κ-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 10β-hydroxy-4,5-epoxymorphinan, exclusively. A stepwise inversion method of the 10β-hydroxy group to produce 10α-hydroxy-4,5-epoxymorphinan was established. By HPLC analyses, 10α-hydroxy-TRK-820 12 was confirmed to be one of the degradation products in developing formulation of TRK-820.