Optical enrichment chromatography

One-pot synthesis, prostaglandins, 302 Opiates, 36 Optical enrichment chromatography, 285 sublimation, 280... 

To a mixture of the acid (la-f, 2.5 mmol) and racemic 2-ethyIhexyl amine (2, 5.0 mmol), CAL-B (300 mg) was added. The reaction mixture was heated at 90 °C in vacuo with stirring and the progress of the reaction was monitored by IR spectroscopy. When the acid was consumed completely, the reaction mixture was diluted with dichloromethane and quenched by filtering off the enzyme. The organic solvent was evaporated in vacuo and the residue was subjected to column chromatography using petroleum ether-ethyl acetate as eluent to afford the pure amide and the unreacted amine in optically enriched forms. 

Prior to the mid-sixties some instances of the resolution of racemates by chromatography on chiral solids were known, e.g., the optical enrichment of Troe-ger s base on D-lactose achieved by Prelog and Wieland [6]. Some notice was taken of these early observations, but it was generally thought that such processes would be inefficient and limited in scope. As to the separation of enantiomers on chiral liquids, serving as stationary phases in GC, the intuitive feeling of chemists was that the differences in solubility of antipodes could not possibly be sufficient to permit resolution. However, when a determined effort was initiated to investigate this approach, it was soon found that these preconceptions were erroneous. 

Quallich, Process for the production of enantiomerically pure or optically enriched sertraline-tetralone using continuous chromatography. US Patent 6,444,854 (2002). 

A new approach to the resolution of sulphoxides 242 was recently reported by T oda and coworkers282. It takes advantage of the fact that some sulphoxides form crystalline complexes with optically active 2,2 -dihydroxy-l, 1-binaphthyl 243. When a two-molar excess of racemic sulphoxide 242 was mixed with one enantiomeric form of binaphthyl 243 in benzene-hexane and kept at room temperature for 12 h, a 1 1 complex enriched strongly in one sulphoxide enantiomer was obtained. Its recrystallization from benzene followed by chromatography on silica gel using benzene-ethyl acetate as eluent gave optically pure sulphoxide. However, methyl phenyl sulphoxide was poorly resolved by this procedure and methyl o-tolyl, methyl p-tolyl, s-butyl methyl and i-propyl methyl sulphoxides did not form complexes with 243. 

The precision of enantiomeric purity determinations by gas chromatography is high123 124-1 >s. This statement holds not only for small enantiomeric purities ( 0% ee), e.g., in the differentiation of a true racemate from enantiomerically slightly enriched mixtures (in reactions devoted to the amplification of optical activity under prebiotic conditions), but also for very high enantiomeric purities (— 100% ee), with detection of 1.0 to 0.1% (and less) of enantiomeric impurities (see Section 3.1.5.8). It is always advantageous if the enantiomer present as an impurity is eluted as the first peak from the gas chromatographic column (Section 3.1.5.3.). This is achieved by the proper selection of the chirality of the nonracemic stationary phase147-188 which, unfortunately, is not possible for the cyclodextrin phases. 

Chromatography. Under certain conditions, even homochiral and het-erochiral self-assemblies can be separated by achiral methods. Thus, chromatography of partially resolved enantiomers can cause depletion or enrichment of enantiomers on achiral stationary phases with an achiral mobile phase. 14C-Labeled nicotine was first resolved into its enantiomers by high-performance liquid chromatography (HPLC) on an achiral stationary phase (Partisil-ODS or -SCX) through coinjection with optically active nicotine (59). This observation was followed by resolution of a number of chiral compounds by chromatography (<50-62) (Scheme 34). When a chiral diamide in 74% ee was separated on a Kieselgel 60... 

The separation methods described in Section IV for pairs of optically active diastereoisomers have also been applied to mixtures of diaste-reoisomeric pairs of enantiomers. By one or other of the following methods, it was possible to separate diastereoisomeric pairs of enantiomers completely or, at least, to obtain enriched fractions. In chromatography under achiral conditions, enantiomers are eluted at identical rates. Therefore, the.pairs of enantiomers (RR )l(SS ) and (RS )I(SR ) can be separated chromatographically in the same way as a pair of optically active diastereoisomers (RS1) and (SS ). By application of the methods based on solubility differences for many examples, fractions containing the less soluble pair of enantiomers could be separated from fractions containing the more soluble pair of enantiomers. However, with respect to the separation.by solubility differences, the situation with two diastereoisomeric pairs of enantiomers is more complicated than that of a pair of... 

Preparative enrichment of enantiomers should be followed by determination of their chemical and enantiomeric purities, e.g., by enantioselective liquid chromatography.25,26 In addition to the sorbents mentioned above, others may be used which are available in only smaller amounts. In our laboratory, this is true for (+)-poly(trityl methacrylate) on silica,35 which can be used for analytical purposes. Preparative separations on a column 0.5 cm in diameter, however, would require many injections of small amounts of racemate. In the case of a baseline chromatogram like that in Figure 2, the determination of enantiomeric purity by measurement of the two peak areas of the enantiomers is straightforward. An analytical chromatogram showing some separation by photometric detection in spite of peak overlap (Figure 4) can still be used for optical purity determina-tion. The simultaneous use of both photometric and chiroptical detection as... 

Cyclodextrins have previously been successfully employed in separation science. For instance, the partial separation and enrichment of optical and structural isomers as well as routine compounds based on selective precipitation with CDs have been reported [5,7-8]. Additionally, solutions of CDs have served as the mobile phase in a few thin-layer and high performance liquid chromatographic separations [5,9,10]. However, their most widespread application in chromatography has been as part of the stationary phase [5,6]. Various polymeric CD materials, CD gels or resins, as well as CD coated columns have been utilized as the stationary phases in the separation of many important classes of compounds [5,6,11-13]. Unfortunately, the use of these CD phases has been largely restricted to column or gas chromatography due to their low efficiency and/or poor mechanical strength [14-16]. 

It has been shown in our laboratory [35] that a-amino acid derivatives, such as N-lauroyl-L-valine t-butylamide and N-TFA-val-valine-cyclohexyl ester, of 70% optical purity, could be enriched to 90-100% by chromatography on silica gel with an organic eluant in the absence of a chiral reagent (see Fig. 4). 

Optically active allylboronates bearing chiral auxiliary located at the boron atom found widespread applications in asymmetric synthesis. Enantiomerically enriched a-alkylidene-y-lactones and lactams can also be synthesized following such a synthetic approach. VUlieras et al. (41, 45] demonstrated the potential of chiral allylboronates derived from 2-phenyl-2,3-bomanediol, ephedrine, or norephedrine for this purpose. Chiral allylboronates 46a,b were obtained in a sequence of reactions involving transformation of achiral precursors 32 into the corresponding boronic acids 44 followed by their esterification with enantiomerically pure diol or 1,2-aminoalcohol 45 (Scheme 4.10). In the case of methyl-substituted derivatives 32b (R = Me), initial composition of E- and Z-isomers was transferred to the target allylboronates 46b. Importantly, the isomeric mixture was separated by means of the column chromatography. 

By recycle chromatography we tried to improve the resolution 500 mg of DL-2-phenyl glycine (VII) were eluted from polymer 11 with O.lA HCl. The optically active fractions were collected just up to the fraction with the highest negative rotation value, evaporated and submitted to several adsorption-elution chromatographic cycles. Afther the fifth cycle the optical purity of the first three fractions was 95%, 73% resp. 56% and an optical total enrichment of 19% was achieved. 

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