N-acetyl-phenylalanine

Subtilisin generally shows poor transesterification activity in water-free ionic liquids, but Shah and Gupta [73] studied various approaches to maintaining its activity. The best results-up to 10000 times increase in the initial rate N-acetyl-phenylalanine ethyl ester in [BMIm] [PF6]-were obtained by precipitating and washing with 1-propanol. 

Petkov and Stoineva (12) have more recently reported that the relative rate of the o-chymotrypsin-catalyzed hydrolysis of p-alkoxycarbonyl anilide derivatives 35 of N-acetyl-(.-phenylalanine is enhanced with an increase in the size of the R alkyl group of the leaving group. This rate enhancement specificity appears to be entropy controlled the bulky alkyl groups increase both enthalpy and entropy of activation. These kinetic and thermodynamic data were interpreted in the following way the bulky -alkoxycarbonyl... 

Pasta et al. (1989) Batch Transesterification of n-acetyl-phenylalanine chloroethyl ester and ethanol Subtilisin Carlsberg... 

Then acetylbromide was dissolved in this solution, to give a N-acetyl phenylalanine. 

The synthesis of carbohydrate-phosphinites was, however, unexpectedly successful. The preparation was much easier than that of the phosphanes. The products could be obtained in crystalline state and were less sensitive to oxidation by air. Their thermal stability was high and drying could be done in vacuum up to 100 °C without decomposition. The rhodium(I) chelate of methyl 4,6-O-benzyli-dene-2,3-bis(0-diphenylphosphino)-a-D-glucopyranoside led to 75% ee (S)-N-acetyl-phenylalanine 2a on hydrogenation of (Z)-2-acetamidocinnamic acid la (Fig. 2) [6],... 

Petkov, Christova, and Stoineva (11) have reported a study on the hydrolysis of N-acetyl- -phenylalanine anilide derivatives with a-chymotrypsin N-methylated anilides 34 (R CHg) were found to be unreactive under the conditions used for the hydrolysis of N-H anilides 34 (R=H). These authors have explained their results in a manner analogous to that described above, i.e. no hydrolysis takes place because steric hindrance caused by the N-methyl group prevents the formation of a tetrahedral intermediate in the N-methyl anilide derivatives. 

The answer concerns the different kinetic behavior of chymotrypsin toward amide and ester substrates. Substrate A is N-acetyf-L-phenyfalanine p-nitrophenyl amide, rather than N-acetyl-L-phenylalanine p-nitrophenyf ester for which the initial burst activity was described in the text. The burst is observed if the first step of a reaction (in this case, acyl-chymotrypsin formation, together with release of p-nitrophenyl amine) is much faster than the second step (release of N-acetyl-phenylalanine and free chymotrypsin). With the amide substrate, however, the relative rates of the two steps are more nearly equal therefore no burst is observed. 

Enzymes other than CAL B have also been reported to operate under the biphasic conditions. CAL A and CAL B or a lipase from Mucor miehei were tested for the kinetic resolution of glycidol using vinyl acetate or vinyl butyrate. The enzymes were used either suspended in the free ILs or immobilized, when the reactions were carried out in [EMIM][NTf2] [71]. CALAwas inactive, butthe other two enzymes showed activity, albeit at 10-20% of that in the absence of COj whether they were free or immobilized. In general, the supported enzymes showed superior performance [71]. Chymotripsin, a specific protease for aromatic amino acids, was found to catalyze the hydrolysis or transesterification of the ethyl ester of N-acetyl-phenylalanine with propanol in scC02-[RMIM][PF5] (R = butyl or octyl) with or without added water [Eq. (15)]. 

The predominant product (>95% ee) of this reaction, however, is the ester of N-acetyl-(/ )-phenylalanine, (i )-41. This requires that the Rh(chiraphos) (olefin) intermediate, (/ ,i )-38, which is in lowest concentration, yields most of the product. This illustrates again that the dominant species observed is not necessarily the most reactive, nor is it necessarily a loop species in the most important catalytic cycle. 

The conglomerate-like behaviour during the fractionated precipitation was observed in case of several chiral acids, too. A good example is the enantiomeric enrichment of N-acetyl-phenylalanine (AcPA). The pure (R)-AcPA isomer was obtained in two steps from its nonracemic enantiomeric mixtures. ... 

The situation was almost the same when the N-acetyl-phenylalanine (AcPA) was reacted with methyl (S)-phenylalaninate (MePA) according to the preceding resolution. The obtained crystalline diastereoisomeric salt also will be a quasi-racemate, but its enantiomeric excess (ee 93%) was even higher than that of the former case. 

For example, when N-acetyl-phenylalanine (AcPA) is resolved with half an equivalent amoimt of (R)-phenylglycine amide (PGA) in presence of sodium hydroxide both the enantiomeric purity and the productivity were lower than when instead of sodium hydroxide half an equivalent amount of benzylamine (BA) was applied (BA has a more related structure with the resolving agent than sodium hydroxide). Its presence improved significantly the crystallization of (S)-AcPA.(R)-PGA diastereoisomeric salt, as well as the efficiency of the resolution... 

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