Enantiomers separation through diastereomer

Since enantiomers have identical physical properties they cannot be separated by physical means. They can be separated by resolution through diastereomers. In this method, enantiomers are converted to diastereomers by reaction with a pure optically active compound. Diastereomers have different physical properties and can be separated. After separation, the diastereomers are converted back to the original enantiomers. 

The development of liquid chromatography on a chiral support gave a decisive impulse to the study of atropisomerism since resolution can be quantitatively performed under very mild conditions without derivatiza-tion. The analytical methods can be easily extrapolated to preparative scale. Several atropisomeric systems, which do not present suitable functional groups to perform classical resolution through diastereomer resolution, can be readily separated into optically pure enantiomers. Dynamic chiral HPLC fills the gap between barriers attainable by DNMR and by thermal racemization of pure enantiomers. Chiral HPLC opens the way to several unexplored domains in the field of atropisomerism. We have... 

The diester enantiomer (108) derived from ribonolactone, has been cyclized and decarboxylated to the bicyclic ketone (109) in 83% overall yield for the two steps (Scheme 38)." Similarly, the cyclopentanol diester (110) has been cyclized and decarboxylated to (111), separation of the two diastereomers being effected on the deprotected alcohols (Scheme 39)." Cyclization of (112) occurs regioselectively as expected to give (113) in 81% yield (equation 32)." The 9-azaprostaglandin skeleton has been formed through a combination of Michael and Dieckmann reactions." ... 

A simple approach to kinetic resolution is to use a stoichiometric reagent. In the example shown in Scheme 1.3, an enantioenriched alcohol is obtained from a racemate through the addition of an enantiopure-acylating agent [13]. If 1 equivalent of the reagent were used, a 1 1 mixture of diastereomers would result with no kinetic differentiation. Stoichiometric kinetic resolutions thus necessarily employ a sub-stoichiometric amount of the reagent - in the example shown only 0.1 equivalents is used. This method for the separation of enantiomers is described in detail by Maddani, Fiaud and Kagan in Chapter 2. 

Mexiletine contains an amino group, and at pH 7, it exists as its conjugate acid that is the amino group is a protonated ammonium ion. When a solution of ( )-mexiletine at pH 7 passes through a column whose chiral hgand is (5)-aspartate, ion pairs between the chiral column matrix and the (+) and (-) forms of mexiletine form transiently. The ion pairs are diastereomers, and the mexiletine enantiomers do not have the same affinity for the column. It turns out that (—)-(i )-mexiletine binds to the column with lower affinity than its enantiomer, and it emerges from the column (elutes) first. A complete separation of enantiomers is the result. 

Resolution of racemates through the diastereomer formation and selective crystallization is a common strategy for chemical separation of enantiomers from racemic mixtures employing chiral resolving agents. The principle of a... 

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