Research progress of resolution of chiral drugs and their synthetic intermediates / 药学学报

Compared with the racemate of chiral drugs, enantiopure chiral drugs have been the hot spot of drug research because of their higher selectivity and lower side-effects. Although remarkable progress of asymmetric synthesis has been achieved in the last decades, chiral resolution is regarded as an important approach to obtain chiral drugs. Recent research advancements in the field of chiral resolution of racemic drugs and intermediates are reviewed here. It is clear that combination of chiral separation and racemization to improve the resolution efficiency has become a trend of chiral resolution. In addition, we also introduce some novel resolution methods, such as chiral extraction, membrane resolution, and resolution using nanoparticles.

Chemical resolution on (±)1-(Benzamidomethyl)-1,2,3,4-tetrahydro-isoquinoline / 中国生化药物杂志

Objective To obtain two types of optical isomers from 1-(Benzamidomethyl)-1,2,3,4-tetrahydro-isoquinoline (BTIQ). Methods ( ±) BTIQ as raw materials , optically pure camphor sulfonic acid as resolution agent was used and repeated resolution in acetone , And the resolution product was detected by specific optical rotation .The product of BTIQ was hydrolyzed , and the ratio of ATIQ was compared with that of the literature .ResuIts After two repeated chemical resolutions , the specific rotations of both enantiomers are no longer changed .It was showed that the products of higher optical purity.The specific rotation of both isomers are -35.65°(CH2Cl2, C=0.5)with the yield of 27.52%,and +35.17°(CH2Cl2, C =0.5) with the yield of 31.55% respectively.The specific rotation value of chiral 1,2,3,4-tetrahydroisoquino line ( ATIQ) which was the hydrolysis product of BTIQ consistent with values reported in the literature .ConcIusion The (-) BTIQ and ( +) BTIQ enantiomers were successfully obtained by the method of resolution , and the yield and optical purity of the obtained products are higher , laying the foundation for the further development of high efficiency , low toxicity of chiral schistosomicide ( praziquantel ) and other containing tetrahydroisoquinoline structure of chiral drugs .