Abstract
Chiral compound plays an important role in biological activities. The pharmacological effects of the individual enatiomers of a drug can be strikingly different. The side effects of chiral drugs are less than the other non-chiral drugs. The purpose of this work is to study the chemical resolution and racemization process of chiral antihistamine and antidepressant drugs. The D-2-[p-Bromo-α-[2-(dimethylamino) ethyl] benzyl]- pyridine is an antihistamine drug with one chiral center. Although this drug was initially developed in the racemic (D,L)-form, the D-form enatiomer has shown a remarkably stronger antihistamine activity than the L-form enatiomer. In this study, new chemical resolution reagents have been prepared from optically active nature amino-acid. The amino-acid derivatives, which have high enatioselectivity, can resolve the racemic compound. After chemical resolution study, the optical purity of chiral antihistamine products are greater than 95%. The (1S,4S)-4-(3,4-Dichloro- phenyl)- 1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine which has two chiral centers is one of the selective serotonin reuptake inhibitors of antidepressant drugs. In this study, a preliminary process for the antidepressant drug has been studied. The process developed herein has several main reactions-acylation, reduction, alkylation, cyclization, reductive amination and chemical resolution. The new chemical resolution reagent of this antidepressant drug is created. By using the new chemical resolution reagent- L form pyroglutamic acid, the optical purity of antidepressant product is greater than 93%. Moreover, to overcome 50% yield of wanted product in the resolution process, this study also develops a racemization process for cis-form compound from the trans-form compound. For the pharmaceutical manufacture, both raw material costs and waste generation can be reduced significantly when chemical resolution and racemization are applied on the chiral chemicals process. The chiral separation by chemical resolution and racemization process herein may be applied to other pharmaceuticals having chiral carbons.