How Can Enantiomers Be Resolved

Resolution Separation of a racemic mixture into its enantiomers. 

Resolution is the separation of a racemic mixture into its enantiomers. Because two enantiomers have the same physical properties, separating them, in general, is difficult, but scientists have developed a number of ways to do it. In this section, we illustrate just two of the several laboratory methods for resolution the use of enzymes as chiral catalysts and the use of solid chiral materials to differentiate between enantiomers made to come in contact with these materials. 

Dopamine decarboxylase is specific for the S enantiomer, which is commonly known as L-DOPA. It is essential, therefore, to administer the enantiomerically pure prodrug. Were the prodrug to be administered in a racemic form, there could be a dangerous buildup of the R enantiomer, which cannot be metabolized by the enzymes present in the brain. 

Following are structural formulas for three other angiotensin-converting enzyme (ACE) inhibitors, all members of the pril family. Which are chiral For each that is chiral, determine the number of stereoisomers possible for it. List the similarities in structure among each of these four drugs. 

One class of enzymes that has received particular attention in this regard is the esterases, which catalyze the hydrolysis of esters (Section 14.1C) to give an alcohol and a carboxylic acid. We illustrate this method by describing the resolution of (f ,5)-naproxen. The ethyl esters of both (R)- and (5)-naproxen are solids with very low solubilities in water. Chemists then use an esterase in alkaline solution to selectively hydrolyze the (S)-ester, which goes into the aqueous solution as the sodium salt of the (5)-carboxylic acid. The (fl)-ester is unaffected by these conditions. Filtering the alkaline solution recovers the crystals of the (i )-ester. After the crystals are removed, the alkaline solution is acidified to precipitate pure (5)-naproxen. The recovered (J )-ester can be racemized (converted to an f ,S-mixture) and again treated with the esterase. Thus, by recycling the (f )-ester, all the racemic ester is converted to (5)-naproxen. 

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