Synthesis and separation of optically active compounds. Part I

Biological processes involve a high degree of stereoselectivity. Considering that pharmacological activity is very often associated with only one enantiomer, regulation authorities have defined new guidelines in requiring chiral drugs to be marketed as pure individually safe and effective enantiomers. If large scale production of pure stereoisomers has met until recently a great difficulty to become economically acceptable, the current state of the art in asymmetric synthesis and chiral separation, provides however many industrial applications. Among the methods currently used, asymmetric synthesis, using chiral auxiliaries or chiral catalysts such as enzymes or metal complexes, allows to create new asymmetric centers, starting from prochiral molecules. Regarding racemate resolution, asymmetric synthesis offers the real economical advantage to produce exclusively the targeted enantiomer. However, resolution methods allowing access to both enantiomers, are very useful at preparative scale for new chiral drugs when preclinical studies are requested for each enantiomer. Large scale racemate resolution can be achieved by crystallization, enzymatic resolution and even more recently by liquid chromatography. Although the "unwanted" enantiomer is also produced, the feasibility of its racemization for recycling has made resolution methods widely used in industry. It is clear today that in most cases, pharmacologically active molecules having an asymmetric center will have to be marketed as optically pure drugs.