Racemization effects

Urethane-protected alkyl N-carboxy anhydrides do not racemize effectively under the conditions established for the dynamic kinetic resolution of aryl N-carboxy anhydrides. As for the l,3-dioxolane-2,4-diones rac-29 (aryl, Scheme 13.12) and rac-15 (alkyl, Scheme 13.8) this different reactivity can be attributed to the lower acidity of the a-CH in the alkyl-substituted anhydrides. To overcome this hurdle Deng and... 

From this result one can see that the asymptotic value 0i)0O decreases as/x decreases. In particular, when/x = 0,4> is independent of q and does not vary 0i,oo = 0i,o- Namely, chirahty amplification by k2 is completely canceled out by the racemization effect caused by k 2. 

Zein, which is the major protein in corn, was chosen because it contains no lysine. This precluded the formation of LAL during alkali treatment. Therefore, any changes in digestibility or uptake could be attributed to racemization effects alone. Additionally, we were interested in comparing the effects of sodium hydroxide treatment with the effects of calcium hydroxide treatment because lime is used in the preparation of corn meal for use in tortillas. If the traditional lime treatment of com meal is unnecessarily harsh, it could have important nutritional consequences because a large segment of the Mexican population obtains much of their dietary protein in the form of tortillas (22). 

The alkaline treatment effects resulting in LAL formation cannot be separated completely from the racemization effects on the amino acids in the protein (, 70). 

Table 2. Cumulative effects of BA application on five main stem 1X93-100 racemes. Effects were measured as the total accumulated 6 weeks after BA treatment. [3]...

It is evident, that, because of racemization effects, no comparable approach according to the Letsinger method in solid-phase synthesis, Le. synthesis from the amino terminus of the peptide has b n reported [2]. This would require polymer supports with different functional groups than those using the conventional carboxyl end of the peptide. 

Pfeiffer effect The change in rotation of a solution of an optically active substance on the addition of a racemic mixture of an asymmetric compound. 

With the dicyclohexylcarbodiimide (DCQ reagent racemization is more pronounced in polar solvents such as DMF than in CHjCl2, for example. An efficient method for reduction of racemization in coupling with DCC is to use additives such as N-hydroxysuccinimide or l-hydroxybenzotriazole. A possible explanation for this effect of nucleophilic additives is that they compete with the amino component for the acyl group to form active esters, which in turn reaa without racemization. There are some other condensation agents (e.g. 2-ethyl-7-hydroxybenz[d]isoxazolium and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline) that have been found not to lead to significant racemization. They have, however, not been widely tested in peptide synthesis. 

Although it might seem that adrninistration of enantiomericaHy pure substances would always be preferred, the diuretic indacrinone (3), is an example of a dmg for which one enantiomer mediates the harmful effects of the other enantiomer (4). (+)-Indacrinone, the diureticaHy active enantiomer or eutomer causes uric acid retention. Fortunately, the other enantiomer distomer) causes uric acid elimination. Thus, adrninistration of a mixture of the two enantiomers, although not necessarily racemic, may have therapeutic value. 

The optical activity of malic acid changes with dilution (8). The naturally occurring, levorotatory acid shows a most peculiar behavior in this respect a 34% solution at 20°C is optically inactive. Dilution results in increasing levo rotation, whereas more concentrated solutions show dextro rotation. The effects of dilution are explained by the postulation that an additional form, the epoxide (3), occurs in solution and that the direction of rotation of the normal (open-chain) and epoxide forms is reversed (8). Synthetic (racemic) R,.9-ma1ic acid can be resolved into the two enantiomers by crystallisation of its cinchonine salts. 

The a-carbon of glutamic acid is chiral. A convenient and effective means to determine the chemical purity of MSG is measurement of its specific rotation. The specific optical rotation of a solution of 10 g MSG in 100 mL of 2 A/HQ is +25.16. Besides L-glutamic acid [56-86-0] D-glutamic acid [6893-26-1] and the racemic mixture, DL-glutamic acid [617-65-2] are known. Unique taste modifying characteristics are possessed only by the L-form. 

Studies of reaction mechanisms ia O-enriched water show the foUowiag cleavage of dialkyl sulfates is primarily at the C—O bond under alkaline and acid conditions, and monoalkyl sulfates cleave at the C—O bond under alkaline conditions and at the S—O bond under acid conditions (45,54). An optically active half ester (j -butyl sulfate [3004-76-0]) hydroly2es at 100°C with iaversion under alkaline conditions and with retention plus some racemization under acid conditions (55). Effects of solvent and substituted stmcture have been studied, with moist dioxane giving marked rate enhancement (44,56,57). Hydrolysis of monophenyl sulfate [4074-56-0] has been similarly examined (58). 

Verapamil. Verapamil hydrochloride (see Table 1) is a synthetic papaverine [58-74-2] C2qH2 N04, derivative that was originally studied as a smooth muscle relaxant. It was later found to have properties of a new class of dmgs that inhibited transmembrane calcium movements. It is a (+),(—) racemic mixture. The (+)-isomer has local anesthetic properties and may exert effects on the fast sodium channel and slow phase 0 depolarization of the action potential. The (—)-isomer affects the slow calcium channel. Verapamil is an effective antiarrhythmic agent for supraventricular AV nodal reentrant arrhythmias (V1-2) and for controlling the ventricular response to atrial fibrillation (1,2,71—73). 

Various racemic secondary alcohols with different substituents, eg, a-hydroxyester (60), are resolved by PFL neatly quantitatively (75). The effect of adjacent unsatuiation on enzyme-catalyzed kinetic resolutions was thoroughly studied for a series of aHyUc (61), propargyUc (62), and phenyl-substituted 2-aIkanols (76,77). Excellent selectivity was observed for (E)-aHyhc alcohols whereas (Z)-isomers showed poor selectivity (76). 

Resolution of Racemic Amines and Amino Acids. Acylases (EC3.5.1.14) are the most commonly used enzymes for the resolution of amino acids. Porcine kidney acylase (PKA) and the fungaly3.spet i//us acylase (AA) are commercially available, inexpensive, and stable. They have broad substrate specificity and hydrolyze a wide spectmm of natural and unnatural A/-acyl amino acids, with exceptionally high enantioselectivity in almost all cases. Moreover, theU enantioselectivity is exceptionally good with most substrates. A general paper on this subject has been pubUshed (106) in which the resolution of over 50 A/-acyl amino acids and analogues is described. Also reported are the stabiUties of the enzymes and the effect of different acyl groups on the rate and selectivity of enzymatic hydrolysis. Some of the substrates that are easily resolved on 10—100 g scale are presented in Figure 4 (106). Lipases are also used for the resolution of A/-acylated amino acids but the rates and optical purities are usually low (107). 

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