Enantiomer enrichment

This amide, readily formed from an amine and the anhydride or enzymatically using penicillin amidase, is readily cleaved by penicillin acylase (pH 8.1, A -methylpyrrolidone, 65-95% yield). This deprotection procedure works on peptides, phosphorylated peptides, and oligonucleotides, as well as on nonpeptide substrates. The deprotection of racemic phenylacetamides with penicillin acylase can result in enantiomer enrichment of the cleaved amine and the remaining amide. An immobilized form of penicillin G acylase has been developed. ... 

Transformation of chiral nitrones into enantiomer enriched a-chiral N -hydroxylamines and their derivatives, has been successfully employed in the enantioselective synthesis of (+ )-(R)- and (—)-(S)-zileuton (216). An expeditious synthesis of thymine polyoxin C (347), based on the stereocontrolled addition of 2-lithiofuran (a masked carboxylate group) to the A-benzyl nitrone derived from methyl 2,3-O-isopropylidene-dialdo-D-ribofuranoside, is described (Scheme 2.151) (194). 

Cathodic deprotection of tosylates of chiral alcohols was achieved without racemization by cleavage of the O—SO2 bond [351]. Optically active quaternary arsonium [352, 353] and phosphonium salts [354] are cathodically cleaved to tertiary arsines and phosphines respectively, with retention of the configuration. The first enantiomer enriched chiral phosphines have been prepared this way. 

The above azomethine ylide cycloadditions have been extended to an enantioselective version involving amino alcohols both as chiral ligands and amine bases. Thus, reactions of the N-metalated azomethine yhdes derived from achiral methyl 2-(arylmethyleneamino)acetates, cobalt(II) chloride [or manganese(II) bromide], and chiral amino alcohols, 1 and 2 equiv each, with methyl acrylate as solvent have been performed to provide the enantiomer-enriched pyrrolidine-2,4-dicarboxylates with the enantioselectivities of up to 96% enantiomeric excess (ee) (128,129). However, a large excess of the metal ions and the chiral source (ligand and base) have to be employed. 

The 1,1-binaphthyl ring system is a key component of a number of chiral ligands that have been used as catalysts for asymmetric synthesis <1992S503>. Chemo- and stereoselective (. )-stannepin-catalyzed monobenzoylation of terminal 1,2-diols 312 afforded ( -enantiomer-enriched 2-benzoylated diols 313 in moderate selectivity. Only a trace of 1-benzoylated diols 314 was observed (Equation 55). Thus, the method was successfully applied to kinetic resolution of racemic 1-phenyl-1,2-ethanol using a chiral organotin catalyst <2000JOC996>. 

S)-Enantiomer-enriched 1-Benzoylated diol 2-benzoyloxy-1 -phenylethanol... 

Formation of Enantiomer-Enriched Epoxides via Lewis Acid-Promoted Asymmetric Cyclization... 

Brack, A. and Spach, G. (1981). Enantiomer enrichment in early peptides. Origins of Life and the Evolution of Biospheres, 11, 135—42. 

There can be no accidental resolution, deresolution, or racemization during a derivatization (but beware of enantiomer enrichment during sample purification, vide supra). 

No kinetic resolution arises as a result of double asymmetric induction in a chiral derivatization scheme, although care must still be taken to avoid enantiomer enrichment (or depletion) during workup (c/. Figure 2.1 and accompanying discussion). 

The first asymmetric synthesis to achieve >90% optical yield was Brown s hydroboration of cis alkenes with diisopinocampheylborane (IpC2BH, Figure 7.10) in 1961 [130,131], The reagent was prepared by hydroboration of a-pinene of 90% ee 2-butanol obtained from hydroboration/oxidation of cw-2-butene had an optical purity of 87%, indicating an optical yield of 90%. ci5-3-Hexene was hydroborated in -100% optical yield. Since then, simple methods for the enantiomer enrichment of lpc2BH (and IpcBH2) have been developed [132-134], and enantioselectivities have been evaluated more carefully with the purified material. For example, lpc2BH of 99% ee affords 2-butanol (from cw-2-butene) in 98% ee and 3-hexanol (from ci5-3-hexene) in 93% ee, both determined by rotation (see Table 7.6, entries 1 and 5) [132]. ... 

A large variety of applications using either vapor permeation or pervaporation has been reported. These include the use of pervaporation for the removal of toxic organics from water (Schnabel et al., 1998) and wastewater streams (Moulin et al., 2002), sometimes using hybrid approaches with adsorptive techniques the use of pervaporation membranes in direct methanol fuel cells (Pivovar et al., 1999) and, more recently, the resolution of isomeric mixtures (Kusumocahyo etal., 2004) and membrane-assisted enantiomer enrichment (Paris et al., 2004), in both cases using membranes containing specific complexation agents such as cyclodextrins. 

Urea belongs to the clathrate formers which have been used very early for the resolution of racemates Though the enantiomer enrichment usually is not very effective... 

The coupling of the naphthalene derivatives 25 with 26 using (/ )-BINAP as a chiral ligand provided the (/ )-enantiomer-enriched binaphthyl 27 with 63 % ee, suggesting a possibility of asymmetric syntheses of substituted chiral binaphthyls. The coupling can be extended further to heteroaryl derivatives. Reaction of (2-thienyl)diphenylmethanol (28) with chlorobenzene gave 2-phenylthiophene (29) in 89 % yield. 

The pH of the reaction medium is another important factor for modulating both the activity and enantioselectivity of Lipase OF. The enzyme showed optimal hydrolysis activity at pH 4.0, while the enantioselectivity increased sharply with the decrease in medium pH from 4.0 to 2.2. Based on spectroscopic studies, the enhancement of the lipase activity and enantioselectivity at the lower pH could be attributed to the changes in the flexible and sensitive conformation of the lipase induced by tuning the biocatalyst microenvironment. Using a hybrid strategy by modulating pH and surfactant, enantiomer-enriched (5)-ketoprofen could be obtained with 95.5% ee and 39.1% yield from rac-ketoprofen chloroethyl ester (100 mM) at pH 2.5 in the presence of 0.5% (w/v) Tween-80 as a modulator. ... 

Kinetic resolutions (KR) are reactions that occur at different rates with the two enantiomers of a chiral substrate. A kinetic resolution generates two sets of chiral, non-racemic materials. It generates a non-racemic mixture of the substrate enantiomers enriched in the less reactive of the two enantiomers, and it generates a non-racemic mixture of the product resulting from the predominant reaction of the more reactive enantiomer of the substrate. Because the reactant and product have different physical properties, they can be separated more easily than two enantiomers. 

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