Drugs enantioselective toxicity

As discussed above, enantiomers of chiral pollutants may have different toxicities to biota, but some reports have been published indicating more toxicities of the racemic mixture in comparison to the pure enantiomers, which may be due to the catalytic properties of one enantiomer with respect to another. The concept of chirality has been explored to a greater extent in drugs and pharmaceuticals but, unfortunately, the enantioselective toxicities of the chiral pollutants have not been fully investigated in detail. Because of the different toxicities of the enantiomers, data on the toxicity of the racemic pollutant are not reliable. Therefore, it is essential to explore the enantioselective hazardous effects and toxicities of chiral pollutants. Moreover, the already existing data on the hazardous effects and toxicities of chiral pollutants should be modified in terms of the enantioselective toxicities. 

The selectivity of a chemical reaction is a very important criterion. Besides the chemo- and regioselectivity, the stereoselectivity, i.e. the favored or excluded formation of one or several stereoisomers in the course of a chemical reaction, plays an important role. If there is a formation of (S)- and (K)-enantiomers from a prochiral compound, an enantioselective reaction takes place. What are the reasons for the growing interest in enantioselective reactions and preparation of homochiral compounds Firstly, it is certainly the wish of the chemist to imitate the ability of nature by stereospecific synthesis in the laboratory. Secondly, there are some practical and economic reasons many natural products and a great number of synthetic drugs have a chiral structure and the enantiomers can differ markedly in their biological activity. Sometimes only one of the enantiomers exhibits the wanted optimal activity, while the other is less active or totally inactive, or even toxic. 

An a-acetoxysulfide shown in Scheme 3.16 was used as central chiral building block for the s)mthesis of Lamivudine, a highly promising drug candidate for the treatment of HIV and HBV infections. Due to the different toxicities of the two enantiomers, an enantioselective route was required. Furthermore, applicability to large-scale synthesis and absence of any unwanted enantiomers were important issues particularly in view of the possible drug application. 

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