Komatsu T, Yano M, Iwamoto M, Kobayashi M, Suzuki K
Omiya Research Laboratory, Nikken Chemicals Co., Ltd., Saitama, Japan.
Yakugaku Zasshi. 1995 Dec;115(12):1022-6. doi: 10.1248/yakushi1947.115.12_1022.
The two dihydroxylated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate (NIK-247), which is a new drug for the treatment of dementia, were synthesized to determine their chemical structures. Reduction of the tricyclic diketone, 9-amino-2,3,6,7-tetrahydro-1H-cyclopenta[b]quinoline-1,8(5H)-dione, with equivalent molar of NaBH4, afforded the racemic two alcohols, (+/-)-9-amino-2,3,5,6,7,8-hexahydro-8-hydroxy-1H-cyclopenta[b]quinoli n-1-on e and (+/-)-9-amino-2,3,5,6,7,8-hexahydro-1-hydroxy-1H-cyclopenta[b]quinoli n-8- one. (+)-9-Amino-2,3,5,6,7,8-hexahydro-8-hydroxy-1H-cyclopenta[b]quinolin+ ++-1-one was obtained by optical resolution of the corresponding racemic hydroxyketone using (-)-di-p-toluoyl-L-tartaric acid. The optically active dihydroxylated metabolites were obtained by reduction of the (+)-8-hydroxy-1-one with NaBH4.
9-氨基-2,3,5,6,7,8-六氢-1H-环戊并[b]喹啉盐酸盐一水合物（NIK-247）是一种治疗痴呆症的新药，合成了其两种二羟基化代谢物以确定其化学结构。用等摩尔的硼氢化钠还原三环二酮9-氨基-2,3,6,7-四氢-1H-环戊并[b]喹啉-1,8(5H)-二酮，得到外消旋的两种醇，(±)-9-氨基-2,3,5,6,7,8-六氢-8-羟基-1H-环戊并[b]喹啉-1-酮和(±)-9-氨基-2,3,5,6,7,8-六氢-1-羟基-1H-环戊并[b]喹啉-�-酮。使用(-)-二对甲苯甲酰基-L-酒石酸通过相应外消旋羟基酮的光学拆分得到(+)-9-氨基-2,3,5,6,7,8-六氢-8-羟基-1H-环戊并[b]喹啉-1-酮。通过用硼氢化钠还原(+)-8-羟基-1-酮得到光学活性的二羟基化代谢物。
