Enantiomer consumption

The s-values for the lipase route and the phosphine route were not the same, but this is less important than the rates of enantiomer consumption being equal. Hence the relative amounts of lipase and phosphine were adjusted so that the rates of enantiomer consumption were equal. At the end of the reaction, one enantiomer of alcohol is bound to the polymer and the other has formed an ester in solution. They may be separated by filtration. Both reactions have products of higher ee s than predicted for the simple kinetic resolution reactions at 50% conversion. Note that really quite different reagents were used to react with the two enantiomers. 

A first class of monomers obeys equation with first order in enantiomer consumption. One can write for each enantiomer ... 

The ratio of relative rates of enantiomer consumption could take the following expressions ... 

In the case of f-butyl thiirane, the active sites seem to be formed through an equilibrium reaction and the stereoelectivity is temperature dependent. This leads to a second order election law for enantiomers consumption rates. 

Since the first separation of enantiomers by SMB chromatography, described in 1992 [95], the technique has been shown to be a perfect alternative for preparative chiral resolutions [10, 21, 96, 97]. Although the initial investment in the instrumentation is quite high - and often prohibitive for small companies - the savings in solvent consumption and human power, as well as the increase in productivity, result in reduced production costs [21, 94, 98]. Therefore, the technique would be specially suitable when large-scale productions (>100 g) of pure enantiomers are needed. Despite the fact that SMB can produce enantiomers at very high enantiomeric excesses, it is sometimes convenient to couple it with another separation... 

Resin consumption is low because of the highly efficient use of the capacity of the resin for the enantiomer during each cycle, as well as the material stability of the resin. The above benefits of the ChiraLig M technology result in improved economics for the large-scale separation. 

The graph in Fig. 10.12 shows that the purity decreases very quickly below acceptable levels as retention factor of the more retained enantiomer decreases. Flowever, with minor adjustment of the SMB internal flow rates, a variation of more than 10 % of the retention factor of the more retained enantiomer still meets required purity, productivity, and eluent consumption. Control of critical parameters such as retention factors can be made without modification of the feed and eluent flowrates. 

Despite its widespread application [31,32], the kinetic resolution has two major drawbacks (i) the maximum theoretical yield is 50% owing to the consumption of only one enantiomer, (ii) the separation of the product and the remaining starting material may be laborious. The separation is usually carried out by chromatography, which is inefficient on a large scale, and several alternative methods have been developed (Figure 6.2). For example, when a cyclic anhydride is the acyl donor in an esterification reaction, the water-soluble monoester monoacid is separable by extraction with an aqueous alkaline solution [33,34]. Also, fiuorous phase separation techniques have been combined with enzymatic kinetic resolutions [35]. To overcome the 50% yield limitation, one of the enantiomers may, in some cases, be racemized and resubmitted to the resolution procedure. 

The identification of a novel BVMO from Mycobacterium tuberculosis (BVMOMtbs) complements this toolbox, as this particular biocatalyst performs a classical kinetic resolution instead of a regiodivergent oxidation vith complete consumption of substrate [140]. Notably, this enzyme accepts only one ketone enantiomer and converts it selectively to the abnormal lactone while the antipodal substrate remains unchanged (Scheme 9.24) [141]. 

In a NMR tube, to a solution of the epoxy alcohol (2.5 mg) in CDCI3 (0.5 mL) was added 4-dimethylaminopyridine (5 mg) and (R)-(+)-a-methoxy-a-(trifluor-omethyl)phenylacetyl chloride (5 mg). The mixture was allowed to stand overnight at room temperature. The reaction was monitored by TLC to ensure complete consumption of the starting material. H and 19F NMR spectra were carried out on the crude reaction mixture. In the 19F NMR spectrum, each enantiomer gave a signal an additional signal at —71.8 ppm was ascribed to residual MTPA. (19F NMR (250 MHz, CDCI3) 8 - 70.7 (s, (2R,3R)-enantio-mer) —72.0 (s, (25 ,3.S)-enantiomer)). 

The kinetic resolution using a chiral zirconocene-imido complex 286 took place with high enantioselectivity to result in chiral allenes 287 (up to 98% ee) (Scheme 4.74) [116]. However, a potential drawback of these methods is irreversible consumption of half of the allene even if complete recovery of the desired enantiomer is possible. Dynamic kinetic resolutions avoid this disadvantage in the enantiomer-differentiating reactions. Node et al. transformed a di-(-)-L-menthyl ester of racemic allene-l,3-dicarboxylate [(S)- and (RJ-288] to the corresponding chiral allene dicarbox-ylate (R)-288 by an epimerization-crystallization method with the assistance of a catalytic amount of Et3N (Scheme 4.75) [117]. 

FIGURE 4.19 Amino acid enantiomers are determined by reaction (A) with l- or D-amino-acid oxidase at pH 7-8.75 Added catalase decomposes the hydrogen peroxide (B), which would otherwise oxidize the a-oxoacid. Quantitation is achieved by measuring oxygen consumption, which is 0.5 mol/mol of substrate. 

Carbonylative kinetic resolution of a racemic mixture of trans-2,3-epoxybutane was also investigated by using the enantiomerically pure cobalt complex [(J ,J )-salcy]Al(thf)2 [Co(CO)4] (4) [28]. The carbonylation of the substrate at 30 °C for 4h (49% conversion) gave the corresponding cis-/3-lactone in 44% enantiomeric excess, and the relative ratio (kre ) of the rate constants for the consumption of the two enantiomers was estimated to be 3.8, whereas at 0 °C, kte = 4.1 (Scheme 6). This successful kinetic resolution reaction supports the proposed mechanism where cationic chiral Lewis acid coordinates and activates an epoxide. 

CE has been established as a very efficient technique for the separation of drug enantiomers. Chiral separations in CE are also based on the formation of diastereomeric complexes between the enantiomers and a chiral selector. The main advantages of the technique are its high efficiency, short analysis times, versatility due to the great variety of chiral selectors that can be added to the BGE, short equilibration times required when changing the chiral selector and low consumption of selector. °... 

Polymerization of racemic 3-methylpent-l-ene (MP) using an optically active catalyst may give an optically active polymer by a polymerization that is partially asymmetric preferential consumption of one of the two enantiomers leaves a monomer mixture having optical activity. 

The process daily throughput is linked to both the injected amount per run and the time between two successive injections. This time has to be minimized using stacked injections in order to optimize the process productivity and further decrease the eluent consumption. Minimum time between two successive injections corresponds to the time needed for eluting the two enantiomer peaks. Under the selected conditions, this time was equal to 100 s. 

Substance Type of Separation e.s./p.p. Company Stationary Phase Productivity (g/Enantiomer or Product/Day kg Stationary Phase) Solvent Consumption (1/g Enantiomer or Product) Ref. 

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