Komatsu T, Yano M, Inada H, Iwamoto M, Okada K, Suzuki K
Omiya Research Laboratory, Nikken Chemicals Co., Ltd., Saitama, Japan.
Yakugaku Zasshi. 1995 Dec;115(12):1016-21. doi: 10.1248/yakushi1947.115.12_1016.
The two mono-hydroxylated 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 two tricyclic ketones, 9-amino-1,2,3,5,6,7-hexahydro-8H-cyclopenta[b]quinolin-8-one and 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]-quinolin-1-one, with NaBH4 afforded the corresponding racemic alcohols. The optically active mono-hydroxylated metabolites, (+)-9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-8-ol and (+)-9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-1-ol, were obtained by optical resolution of each racemic alcohol using (+)-di-p-toluoyl-D-tartaric acid.
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，合成了其两种单羟基化代谢物以确定它们的化学结构。用硼氢化钠还原两种三环酮，即9-氨基-1,2,3,5,6,7-六氢-8H-环戊并[b]喹啉-8-酮和9-氨基-2,3,5,6,7,8-六氢-1H-环戊并[b]喹啉-1-酮，得到相应的外消旋醇。通过使用（+）-二对甲苯甲酰基-D-酒石酸对每种外消旋醇进行光学拆分，得到光学活性的单羟基化代谢物，（+）-9-氨基-2,3,5,6,7,8-六氢-1H-环戊并[b]喹啉-8-醇和（+）-9-氨基-2,3,5,6,7,8-六氢-1H-环戊并[b]喹啉-1-醇。
