Resolving reagent, chiral chromatography

All of the methods for synthesizing amino acids we have described produce racemic mixtures. We recall, however, that racemic mixtures can be resolved by chiral chromatography (Section 8.8). We can also use organometallic reagents as chiral catalysts (Section 17.8) to produce chiral amino acids, as we will see in the next section. 

Synthetic chiral adsorbents are usually prepared by tethering a chiral molecule to a silica surface. The attachment to the silica is through alkylsiloxy bonds. A study which demonstrates the technique reports the resolution of a number of aromatic compoimds on a 1- to 8-g scale. The adsorbent is a silica that has been derivatized with a chiral reagent. Specifically, hydroxyl groups on the silica surface are covalently boimd to a derivative of f -phenylglycine. A medium-pressure chromatography apparatus is used. The racemic mixture is passed through the column, and, when resolution is successful, the separated enantiomers are isolated as completely resolved fiactions. Scheme 2.5 shows some other examples of chiral stationary phases. 

The hydrocarbon 25 has been partially resolved by asymmetric complexation with Newman s reagent [TAPA ( )-a(2,4,5,7-tetranitro-9-fluorenylideneaminooxy)prop-ionic acid] thereby establishing its chiral Z)2-structure 53). Similarity, the naphthaleno-phane 27b could be resolved by chromatography on silicagel coated with (—)-TAPA 49) and recently also by HPLC on optically active poly(triphenylmethyl methacrylate)49a) which also proved to be very useful for the optical resolution of many other axial and planarchiral aromatic compounds 49b>. 

A racemic form is 50 50 mixture of enantiomers. It is optically inactive. A racemic mixture of configurational isomers cannot be separated (resolved) by ordinary chemical means (distillation, crystallization, chromatography) unless the reagent is chiral. One way to separate a pair of enantiomers is to first convert them to diastereomers by reaction with a chiral reagent, then separate the diastereomers and regenerate the (now separate) enantiomers. 

Resolution of alcohols. The reagent is widely used for resolution of chiral alcohols via the diastereometric esters of (- )-camphoric acid formed from 1. Cam-phorates generally have high melting points and can be resolved by fractional crystallization or chromatography. 

Selenoxides derived from unsymmetrical selenides are chiral and stable toward pyramidal inversion at room or even higher temperatures. They are produced enantioselectively by the use of chiral oxidants such as the Sharpless reagent or camphor-derived oxaziridines or diastereoselectively with achiral oxidants when one of the selenide substituents is itself chiral (see Section 9). Racemic selenoxides have been resolved by chromatography over chiral adsorbents. Chiral selenoxides racemize readily in water, particularly under acid-catalyzed conditions, presumably via the intermediacy of achiral selenoxide hydrates (equation 2). 

A number of tetraorganotin (though not yet tetraalkyltin) compounds in which the chirality is centred on the tetrahedral tin centre have been optically resolved by either (a) recrystallisation of the diastereoisomers which are formed with an optically active reagent (e.g. equation 5-1 and 5-2), or (b) by an asymmetric synthesis (e.g. equation 5-3), or (c) by chromatography on microcrystalline cellulose acetate (e.g. equation 5-4).2 These compounds are listed in Table 5-2, where the group which is involved in an asymmetric synthesis is printed in italics. In only a few cases is the optical purity known. 

Pirkle and Simmons [93] used aryl-substituted 2-oxazolidones (35) as chiral derivatization reagents for the resolution of primary amines as their diastereomeric allophanates. The diastereomers contain a semi-rigid backbone through intramolecular hydrogen bonding. The derivatives were separated by liquid chromatography on silica with separation factors between 1.2 and 4. The reagent also reacts with secondary amines but the derivatives are less well resolved. 

A good enantiomeric resolution of a-amino acids was recently achieved by using chiral complexes of copper (II) with A, A -di-n-propyl-L-alanine (DPA) as the additive in the mobile phase. Actually, the mixture of amino acids is separated into four groups by conventional ion-exchange chromatography and then resolved by means of the chiral DPA reagent (Fig. 5). 

The two enantiomers of a given amino acid have identical chemical and physical properties in a symmetrical environment. To resolve such a pair of amino acid by chromatography, diastereomers must be formed. Diastereomers can be formed if a chiral reagent (selector) is introduced to either the mobile or the stationary phase. In case of thin-layer chromatography (TLC), latter manner has largely been used for resolution of amino acids, their PTH-, dansyl, and other derivatives [2,4-6]. 

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