Serine 3- -, ethyl ester

When switching from water to an organic solvent, or switching between organic solvents, the substrate specificity can change. In the example of the standard reaction, transesterification of N-acetyl-i-phenylalanine ethyl ester with n-propanol by Subtilisin Carlsberg, which has been mentioned several times in this chapter already, the relative specificity between the rather hydrophobic phenylalanine compound and its more hydrophilic analog N-acetyl-L-serine ethyl ester varies with the solvent (Table 12.8) (Wescott, 1993). 

Carrara and his colleagues127 prepared 3-(p-nitrophenyl)serine ethyl ester from glycine ethyl ester and p-nitrobenzaldehyde ... 

Serine ethyl ester hydrochloride 1740 2950w, 1450b, 1410w, 1380m, I350w,... 

Synonyms Serine, ethyl ester L-Serine, ethyl ester... 

S)-(+)-Serine. See L-Serine Serine, ethyl ester L-Serine, ethyl ester. See Ethyl serinate... 

N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-alanyl-L-threonyl-L-leucyl-L-alanine p-nitrobenzyl ester)-4-oyl]-N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(L-alanyl-L-threonyl-L-leucyl-L-alanyl-L-serine p-nitrobenzyl ester)-4-oyl]-N-[N-(benzyloxycarbonyl)-L-aspart-1 -oyl-(glycine ethyl ester)-4-oyl -N-[N-(benzyloxycarbonyl)-L-aspart-l-oyl-(glycyl-L-serine methyl ester)-4-oyl]-... 

Selectivity studies with DTU indicated marked discrimination in the clathrate formation 23,45). As in other types of clathrates, the steric factor is important in differentiation between compounds of similar functionality but different shape. For example, DTU forms crystalline complexes with some alcohols (methanol, ethanol, propanol, 1-butanol) but not with others (2-butanol). It complexes the ethyl esters of N-acetyl derivatives of glycine, alanine, methionine and aspartic acid, but not of proline, serine, phenylalanine and glutamic acid. 

Four different amino acids have been selected for esterification to study the effect of R-group substituent of amino acid on rate and ease of esterification. The four acids are alanine, serine, aspartic acid and lysine. Their respective esters were prepared by reported methods to authenticate and compare with those prepared by our method. Alanine was esterified with ethanol to yield the ethyl ester, keeping -NH3+ group intact. This was also confirmed by acidity of final reaction mixture (pH- 3.2). There was about 50% conversion of alanine to its ethyl ester. Further work on ester formation, including qualitative and quantitative analysis, is in process. 

The discovery of oxazoline hydroxamates as potential inhibitors of LpxC was the result of high-throughput screening of large libraries of compounds at the Merck Research Laboratories in collaboration with the Department of Biochemistry, Duke University Medical Center [95]. The lead compound, L-573,655, was a racemic mixture of 4-carbohydroxamido-2-phenyl-2-oxazoline, which had been previously made by Stammer et al. [96] as a precursor in the chemical synthesis of cyclosporine. Namely, (R,S)-serine methyl ester hydrochloride (149) is converted into (R,S)-4-carbomethoxy-2-phenyl-2-oxazoline (150) via treatment with ethyl benzimidate using the Elliot procedure [97]. Treatment of this ester with one equivalent each of hydroxylamine and sodium methoxide in methanol at room temperature affords the desired (R,S)-4-carbohydroxamido-2-phenyl-2-oxazoline (151), as depicted in Scheme 30. 

Ethyl glycidate Oxiranecarboxylic acid, ethyl ester, (R)- (12) (111058-33-4) (S)-Serine L-Serine (8,9) (56-45-1)... 

This procedure describes an efficient method for the synthesis of >99% enantiomerically pure ethyl glycidate from L-serine. Although preparation of potassium glycidate via cyclization of 3-bromo-2-hydroxypropionic acid,2 and from 3-chloro-2-hydroxypropionic acid (obtained by microbial reduction of chloropyruvic acid)3 was previously reported, the corresponding ethyl ester was never described. An enantioselective synthesis of the 2,3-epoxy acid by oxidation of 2,3-epoxypropanol has also been reported.4... 

To a solution of silver triiluoromethanesulfonate (7.71 g, 30 mmol) in dry dichloromethane (100 mL) at —40°C in the dark is added dropwise a solution of 9-fluorenylmethoxycarbonyl serine benzyl ester 11 (8.45 g, 20 mmol), 2,3,4-tri-O-benzoyl-a-D-xylopyranosyl bromide 12 (11.14 g, 21.2 mmol) and tetramethyl urea (3.65 g, 31.4 mmol) in dichloromethane (100 mL). After 18 h of stirring at room temperature, the precipitate is filtered off and washed with dichloromethane (200 mL). The organic solution is washed with water (200 mL), 1% KHCOj solution (twice 200 mL) and water, dried with Na SO, and concentrated in vacuo. The crude product is recrystallized from ethyl acetate-n-hexane. (If the reaction was not complete, chromatography on silica gel 60 in toluene/ethanol 9 1 is recommended). Yield 15 g (87%) mp 136°C, [ot]D -27.8° (c 1.3, CHC13), Rf 0.64 (toluene/ethanol 26 1). 

The protected O-glycosyl amino acid ester or O-glycosyl peptide ester (1 mmol) is stirred in morpholine (10 mL) or morpholine-dichloromethane (1 1) for 30 min. After addition of dichloromethane (100 mL), the solution is washed with diluted aqueous acid (citric acid or HC1 pH 4, 50 mL) and with water (4 x 50 mL), dried with NajSO, and concentrated in vacuo. The crude product is dissolved in 2-5 mL of ethyl acetate. During chromatography on silica gel (50 g) with petrolum ether ethyl-acetate (2 1), W-(9-fluorenylmethyl)morpho-line is eluted. Subsequently, the deblocked amino acid or peptide ester is eluted with methanol. 0-(2,3,4-Tri-0-benzoyl-(3-D- xylopyranosyl)-L-serine benzyl ester 14 yield, 0.63 g (98%) mp 55°C [a]D —41.4 (c 0.5, CH3OH). IV-(L-Asparaginyl-L-leucyl-)-0-(2,3,4,-0-benzoyl-(3-D-xylopyranosyl)-L-serine benzyl ester 17 yield, 0.85 g (98%) amorphous [a]D —42.3° (c 0.5 CH3OH). 

V-(9-Fluorenylmethoxycarbonyl)-0-(2,3,4-tri-0-benzoyl- 3-D-xylopyranosyl)-L-serine 15. The Fmoc O-xylosyl serine benzyl ester 13 (1.0 g, 1.2 mmol) is stirred in methanol (40 mL) at room temperature and subjected to hydrogenolysis for 18 h under atmospheric pressure using palladium-charcoal (0.2 g, 5%) as the catalyst. The educt 13 dissolves slowly. The catalyst is filtered off, and the solvent evaporated in vacuo. If the residue is not pure according to thin-layer chromatography (TLC), it is dissolved in 2 mL of ethyl acetate and purified by chromatography on a short column of silia gel 60. The byproducts are eluted with petroleum ether-ethyl acetate the product 15 with methanol yield 0.85 (92%) mp 109°C, [cr]D -12.6° (c 0.3, CH3OH) Rf 0.64 (toluene-ethanol, 1 2). 

Immobilization in a sol-gel matrix accelerated the propanolysis of N-acetyl-i-phenylalanine ethyl ester in cyclohexane for several serine proteases compared to the non-immobilized lyophilized enzymes 31-fold for Subtilisin Carlsberg, 43-fold for a-chymotrypsin, and 437-fold for trypsin (van Unen, 2001). The activity yield upon immobilization was 90% (a-chymotrypsin). The rate enhancement effect of immobilization on the enzyme activity is highest in hydrophobic solvents. 

An illustrative example of a change in chemoselectivity is the inversion of substrate specificity of the serine protease Subtilisin Carlsberg in the transesterification reaction of ethyl esters of A-acetyl-L-serine and A-acetyl-L-phenylalanine with 1-propanol, measured in twenty anhydrous organic solvents. The enzyme-catalysed reaction with the serine substrate is strongly favoured in dichloromethane, while the reaction with the phenylalanine substrate is preferred in t-butylamine, with a 68-fold change in substrate specificity [313]. 

DIAZOACETATE (ESTER) SERINE see ASA500 DIAZO-ACETIC ACID ESTER with SERINE see ASA500 DIAZOACETIC ACID, ETHYL ESTER see DCN800 DIAZOACETIC ESTER see DCN800 N-DIAZOACETILGLICINA-IDRAZIDE (ITALIAN) see DC0800... 

An efficient and practical two-step [4-1-1] oxazole synthesis utilizes the condensation of serine methyl ester with ethyl imidate 193 to give an intermediate oxazoline 194. Treatment of 194 under basic conditions brings about elimination of hydrogen chloride to give oxazole 195 in high yield (Scheme 54) <20010PD37>. 

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