Resolutions dynamic

The combination of bandwidth and lines of resolution selected for each machine-train must effect separation of the unique frequency components that represent a machine s operating dynamics. Resolution can be improved by reducing Fmax> increasing the lines of resolution, or a combination of both. 

The dynamic resolution of an aldehyde is shown in Figure 8.40. The racemization of starting aldehyde and enantioselective reduction of carbonyl group by baker s yeast resulted in the formation of chiral carbon centers. The enantiomeric excess value of the product was improved from 19 to 90% by changing the ester moiety from the isopropyl group to the neopentyl group [30a]. 

Biocatalytic Deracemization Dynamic Resolution, Stereoinversion, Enantioconvergent Processes and Cyclic Deracemization, in Biocatalysts in the Pharmaceutical and Biotechnology industries, (ed. R.N. Patel), CRC Press, Boca Raton, pp. 27-51. 

Several hundred tons of L-methionine per year are produced by enzymatic conversion in an enzyme membrane reactor. An alternative approach is dynamic resolution, where the unconverted enantiomer is racemized in situ. Starting from racemic /V-acetyl-amino acid, the enantioselective L-acylase is used in combination with an TV-acyl-amino acid racemase to enable nearly total conversion of the substrate. 

Ogilvie monitored the Diels-Alder reaction between cinnamaldehyde and cyclopentadiene by H NMR using his hydrazide catalyst 18 and was able to conclude that under the reaction conditions adopted (18-TfOH 100 mol% CDjNOj/D O (19 1) 0.1 M) cycloaddition was the rate limiting step of the catalytic cycle, iminium ion formation and hydrolysis being rapid [48]. In addition, it was also shown that under these reaction conditions the key cycloaddition step was reversible. Although this unexpected reversibility was slow, the possibility of exploiting this in a dynamic resolution procedure appears tempting. 

SCHEME 24. (-)-Sparteine-induced deprotonation of allyl carbamate 170. Dynamic resolution by crystallization and enantioselective homoaldol reaction... 

Figure 2.6 By resolution of df-amino acid esters under conditions of dynamic resolution 100% of a single enantiomer may be produced. Using catalytic amounts of pyiidoxyl-5-phosphate, which forms a Schiff s base with the ester and not the acid, the unreacted D-ester may be racemised in situ and for instance L-tyrosin has been obtained in 97% ee and 95% yield.

Scheme 7.19 The synthesis of homochiral L-(S)-tert-leucine via a lipase-catalyzed dynamic resolution process.

Fiedler, D., Leung, D.H., Bergman, R.G. and Raymond, K.N. (2004) Enantioselective guest binding and dynamic resolution of cationic ruthenium complexes by a chiral metal-ligand assembly. J. Am. Chem. Soc., 126 (12), 3674-3675. 

With a supply route estabhshed (route 2) and supplies of radafaxine available to fund the initial development activities, focus switched to discovering a more efficient synthesis. Environmental considerations were a key consideration, and a dual program of work was initiated to address these concerns. One approach was to investigate the feasibihty of identifying a Dynamic Resolution to avoid the losses associated with the undesired (R,R)-enantiomer, discussed above, while, in parallel, the viability of employing continuous chromatography to separate the enantiomers was examined. 

Dynamic Resolution of Chiral Amine Pharmaceuticals Turning Waste Isomers into Useful Product... 

I 13 Dynamic Resolution of Chiral Amine Pharmaceuticals Turning Waste Isomers into Useful Product Table 13.3 Enantiomer ratios at different stages of the (IS, 4S)-sertraline mandelate process. 

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