RACEMIZATION, ENANTIOMERIZATION, DIASTEREOMERIZATION, AND EPIMERIZATION - THEIR MEANING AND PHARMACOLOGICAL SIGNIFICANCE

The configurational lability of enantiomers can be characterized by di fferent terms, each defining a specific process. Racemization relates to the macroscopic and statistical process of the irreversible transfo rmation of one of the enantiomers into the racemic mixture. Enantiomer ization refers to the microscopic and molecule process of the reversib le conversion of one enantiomer into the other. Methods allowing the e xperimental determination of rate constants of racemization (k(rac)) a nd enantiomerization (k(enant)) are discussed, and it is shown that k( enant) = 112 K-rac. Neglect of this fact is a source of some confusion in the literature. When two or more elements of chirality are present in a molecule and one of them is configurationally labile, epimerizat ion occurs, a particular case of diastereomerization. These processes of interconversion between diastereomers are kinetically more complica ted than racemization and enantiomerization since the rate constants o f the forward and reverse reactions are always different (k(diast)/A-t o-B not equal k(diast/B-to-A)), however small the difference. An impor tant aspect of the configurational lability of stereoisomeric drugs is the time scale of the phenomenon. When interconversion occurs to a si gnificant extent during the residence time of a drug in the body, a ph armacological time scale is implied. In contrast, the pharmaceutical t ime scale refers to slower rates of interconversion that affect the co nfigurational purity of a drug during its shelf-life. (C) 1995 Wiley-L iss, Inc.