Enantiomeric separation medium

Host-guest inclusion complexations are usually carried out in organic solvents. As a green process, inclusion complexation can be performed in a water suspension medium or in the solid state. When the solid-state reaction in a water suspension medium is combined with an enantioselective inclusion complexation in the same water medium, a one-pot green preparative method for obtaining optically active compounds can be designed. In all these cases, enantiomers separated as inclusion complexes are recovered by distillation of the inclusion complex. When enantioselective inclusion complexation in the solid state is combined with the distillation technique, a unique green process for enantiomeric separation can result. 

Enantiomeric separations of bicyclic acid anhydride 69, lactones 70 and 71 and carboximides 72 and 73 by complexation with la-c in organic solvents were also successful (Table 3.3-3) [26]. These complexations can probably be carried out in a water suspension medium and hence be described as green processes. rac-Panto-lactone (74) was separated to produce (S)-(-)-74 of 99% ee in 30% yield by complexation with Ic [27]. Enantiomerically impure monoterpenes were purified by inclusion complexation with a chiral host compound. For example, (lS,5S)-(-)-verbe-none (75a) of 78% ee gave 99% ee enantiomer by complexation with la. By similar treatment of 75b of 91% ee with la as above, (lR,5R)-(-i-)-75b of 98% ee was obtained [28]. 

Green One-Pot Preparative Process for Obtaining Optically Active Compounds by a Combination of Solid-state Reaction and Enantiomeric Separation in a Water Suspension Medium... 

A new green preparative method for obtaining optically active compounds can be designed using one-pot solid-state reactions and enantiomeric separation processes, carried out continuously in a water suspension medium. Some successful examples are described in this section. 

In this section, one-pot preparations of optically active compounds by a combination of solid-state reaction and enantioselective inclusion complexation in a water suspension medium are described. In order to establish the suspension procedure as a general enantiomeric separation method, enantiomeric separations of various compounds by complexation in hexane and water suspension media were studied. Furthermore, by combining enantioselective inclusion complexation with a chiral host in the solid state with distillation, a fascinating enantiomeric separation method by fractional distillation was established. 

Chen B, Du Y, Wang H. Study on enantiomeric separation of basic drugs by NACE in methanol-based medium using erythromycin lactobionate as a chiral selector. Electrophoresis 2010 31 371-377. 

When a mixture of methyl phenyl sulfide (69a) (1 g, 8.1 mmol), 30% H2O2 (1.84 g, 16.2 mmol), and water (10 ml) was stirred at room temperature for 24 h, rac-lOa was produced (Scheme 11). To the water suspension medium of rac-70a was added 10c (2 g, 4 mmol), and the mixture was stirred for 15 h to give a 1 1 inclusion complex of 10c with (+)-70a. Heating the filtered complex in vacuo gave (+)-70a of 57% ee (0.45 g, 82% yield). From the filtrate left after separation of the inclusion complex, (-)-70a of 54% ee (0.4 g, 73% yield) was obtained by extraction with ether. By the same procedure, optically active 70b-d were also prepared (Table 11). In the case of (+)-70b and (-)-70c,the efficiency of the enantiomeric resolution was very high. 

From other approaches to optically active [2.2]metacyclophanes the following are noteworthy as just mentioned for 64 (medium pressure) liquid chromatography on microcrystalline triacetylcellulose (cf. Ref. 82 ) in ethanol or ether (practicable also at lower temperatures) is a very efficient and successful method for the optical resolution of many axial and planar chiral (aromatic) compounds 83). In many cases baseline-separations can be achieved and thereby both enantiomers obtained with known enantiomeric purity and in amounts sufficient for further investigations, especially for studying their chiroptical properties (see also 3.2 and 3.3). The disub-stituted [2.2]metacyclophanes 57 and 59 (which had been previously correlated to many other derivatives) 78- 79) were first resolved by this method83). 

It thus appears that the enantioselectivity of CALB for this reaction in the solid/ gas bioreactor is similar to that in an organic liquid medium. Solid/gas biocatalysis therefore offers important potential for production of enantiomerically pure compounds, provided that these transformations involve components having a degree of volatility. Furthermore, as the addition of solvents is avoided in this system, separation and purification during downstream processing are simplified, and side reactions are suppressed. 

Similarly, enantiomeric mixtures of carboxylic acid esters can be separated using transesterification (Fig. 22). An n-butanol/water biphasic medium aryloxypropionic acid methyl ester vras transesterified stereoselec-tively, yielding the butylester of the R enantiomer (69). 

The other enantiomer was left untouched by Pseudomonas cepacia lipase (PCL), the enzyme of choice. After reaction is complete, the resolved alcohol must be separated from its enantiomeric acetate 41. It is noteworthy that the enzyme functions in a buffered aqueous acetone medium acetone does not interfere with the action of the enzyme. 

The helical compounds 198a and 199 were separated into the enantiomers by inclusion chromatography (medium-pressure column chromatography on cellulose triacetate). 200 was enantiomerically enriched (—)-200 was only weakly enrich-... 

The last two methods seem to be more promising for preparative asymmetric photochemistry. When a photochemical reaction of a chiral molecule creates new asymmetric centers, the diastereoisomers will not only be produced in different amounts, but may also be separated easily in pure forms. Finally, the most exciting method to induce chirality involves photochemical transformations in a chiral medium, so that several enantiomerically pure molecules are produced without any destruction of the chiral inductor. Irradiation of chiral solutions, enabling strong interactions between a chiral catalyst and photochemically produced intermediates, have recently been used with some success [3]. 

Chromatography can also be used to separate chiral forms of molecules. Given the necessity for a chiral environment to differentiate enantiomeric forms, resolution can only be achieved where the chromatographic medium is chiral and/or the eluent is chiral. As... 

Enantiomers need an isotropic medium to show different properties. In separation methods, there are three ways to make enantiomers and chiral selectors interact (1) a chiral derivatization agent can be used to react with the enantiomeric pair turning it into a diastereoisomeric pair that can be separated by classical means (2) a chiral selector can be added to the mobile phase so that labile diastereoisomers can be formed with the enantiomeric pair during the separation process. Again a classical column will be able to separate the formed diastereoisomers (3) a chiral selector can be attached to the stationary phase. Labile diastereoisomers can be formed with the chiral stationary phase (CSP) producing different progression of the two enantiomers within the chiral column. 

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