ABSTRACT
Chemical synthesis results in the formation of an optically inactive racemate containing an equal amount of two stereoisomers with identical physico-chemical properties but differing in their property to rotate the plane of polarized light: one enantiomer will rotate the plane in the right direction, (dextrorotatory, d or +) while its antipode will rotate in the opposite direction with the same magnitude (levorotatory, l or −). This optical characteristic, however, does not reflect the three-dimensional configuration of the molecule. A preferred nomenclature system incorporating the three-dimensional configuration of the chiral molecule is based on assigning a priority to atoms attached to the racemic carbon according to the Cahn-Ingold-Prelog rules [1]. Prefixes R-(rectus) and S-(sinister) are assigned to the enantiomers on the basis of their absolute configuration. No relationships exist between the d and l versus R and S nomenclatures. For example, the active S-enantiomer of ibuprofen is dextrorotatory (d or +) while that of verapamil, also an S-enantiomer, is levorotatory (l or –). The more active enantiomer is termed the “eutomer,” and the less active the “distomer.” The distomer is often incorrectly viewed as a passive component of the racemate with little pharmacological or pharmacokinetic (PK) significance. However, in some cases, the distomer may act as an agonist or antagonist at the receptor site or compete for drug metabolizing enzymes and binding sites. In other cases, the two stereoisomers may have different pharmacological effects, and administration of a racemate would represent a combination drug product (e.g., indacrine [2]).
