2018-61-3Relevant articles and documents
Thermodynamics of the Hydrolysis of N-Acetyl-L-phenylalanine Ethyl Ester in Water and in Organic Solvents
Tewari, Y. B.,Schantz, M. M.,Pandey, P. C.,Rekharsky, M. V.,Goldberg, R. N.
, p. 1594 - 1601 (1995)
Equilibrium measurements have been performed on the α-chymotrypsin-catalyzed hydrolysis reaction of N-acetyl-L-phenylalanine ethyl ester to (N-acetyl-L-phenylalanine + ethanol) with carbon tetrachloride, dichloromethane, toluene, and aqueous phosphate buffer as solvents for the reactants and products.Apparent equilibrium constants were measured as a function of temperature for this reaction in all four solvents.Calorimetric measurements were also performed for this reaction in aqueous phosphate buffer.The principal reaction occurring in the aqueous phosphate buffer at pH = 6-7 is N-acetyl-L-phenylalanine ethyl ester(aq) + H2O(aq) = N-acetyl-L-phenylalanine(-)(aq) + ethanol(aq) + H(+)(aq).Therefore, to compare the results for the reaction in water with those for the reaction in the organic solvents where it is assumed only neutral species are present, it was necessary to adjust the experimental results to the reaction involving neutral species: N-acetyl-L-phenylalanine ethyl ester(sln) + H2O(sln) = N-acetyl-L-phenylalanine(sln) + ethanol(sln), where sln denotes either aqueous media, carbon tetrachloride, dichloromethane, or toluene.The values of the equilibrium constant for this latter reaction, with the concentration of water included in the expression for the equilibrium constant, ranged from 0.057 to 0.20 at T = 298.15 K for the four solvents.This rather limited range of values for the equilibrium constants is significant.The very limited amount of information available from the literature is also suggestive of the rule that equilibrium constants for hydrolysis reactions in different solvents are comparable if the reaction refers to neutral species and the concentration of water is included in the formulation of the equilibrium constant.Also, the standard molar enthalpy of reaction was found to be a linear function (slope = 313 K) of the standard molar entropy of reaction.This is indicative of an enthalpy-entropy compensation effect.
A facile microwave-mediated drying process of thermally unstable / labile products
Pinchukova,Voloshko,Shyshkin,Chebanov,Van De Kruijs,Arts,Dressen,Meuldijk,Vekemans,Hulshof
, p. 1130 - 1139 (2010)
The drying behavior of (S)-N-acetylindoline-2-carboxylic acid, precipitated (1a, 17 wt %) and nonprecipitated (1b, 5 wt %), and N-acetyl-(S)-phenylalanine ((S)-2-acetamido-3-phenylpropanoic acid, 2), both pharmaceutical intermediates, and of cocarboxylase hydrochloride (thiamine pyrophosphate, 3), a coenzyme, a bioactive form of vitamin B1, being a thermolabile substance, has been determined in straightforward drying setups. The method of supplying energy to the system had a profound influence on the drying rate and on the internal temperature of the samples during drying. The drying time of (S)-N-acetylindoline-2-carboxylic acid (1b) with the low moisture content (5 wt %) could be reduced by a factor 4 using microwave irradiation instead of conventional heating, while keeping the sample temperature under 35 °C. N-Acetyl-(S)-phenylalanine (2) with a higher moisture content (22 wt %) demonstrated a decrease in drying time by a factor 2.5 to 4 depending on the applied microwave powers. A reduction in drying time of the precipitated (S)-N-acetylindoline-2-carboxylic acid (1a, 17 wt % moisture) by a factor 2 was demonstrated for drying at 150 W of microwave irradiation instead of using a water bath at 70 °C. A dramatically shorter drying time by a factor 10 was found for cocarboxylase hydrochloride (3, 15 wt % water) on lab-scale which could be reproduced on pilot-plant scale. To achieve with conventional heating similar drying times as under microwave irradiation for the four examples, extremely high energy inputs should be applied, necessitating extremely high temperature differences between the heating source and the sample. The results reveal that microwave irradiation is less energy-consuming and is particularly useful for effective drying of thermally unstable materials in short periods of time.
ASYMMETRIC HYDROGENATION BY CHIRAL AMINOPHOSPHINE-PHOSPHINITE RHODIUM COMPLEXES
Cesarotti, E.,Chiesa, A.,D'Alfonso, G.
, p. 2995 - 2996 (1982)
The ligands (S)-N-(diphenylphosphino)-2-diphenylphosphinomethylpyrrolidine, (S)-prolophos, and (S)-1-diphenylphosphinoxy-2-N-ethyl-N-diphenylphosphinoaminobutane,(S)-butaphos, have been prepared.The Rh(I) complexes of these phosphines act as an efficient homogenous hydrogenation catalysts at ambient temperature and pressure for α-N-acetaminoacrylic acid and itaconic acid.
Chymotrypsin-catalyzed peptide synthesis in deep eutectic solvents
Maugeri, Zaira,Leitner, Walter,Dominguez De Maria, Pablo
, p. 4223 - 4228 (2013)
Deep eutectic solvents (DESs) are formed by mixing quaternary ammonium salts (e.g., choline chloride) and hydrogen-bond donors (e.g., glycerol or urea), which leads to biodegradable and readily available ionic solvents at room temperature. Analogous to other ionic liquids, DESs represent a promising reaction media if hydrophobic and hydrophilic substrates need to be combined. This paper assesses DESs as reaction media for chymotrypsin-catalyzed peptide synthesis. After careful determination of the reaction conditions (e.g., water content, enzyme loading), α-chymotrypsin displayed high activity for peptide synthesis in choline chloride/glycerol mixtures to afford productivities of ca. 20 g L-1 h-1 and with complete selectivity for the peptide, which is in contrast to the detrimental hydrolysis pathway observed in aqueous media. The nonimmobilized suspended enzyme could be reused several times by simple filtration with excellent to moderate activities. Overall, the results reported suggest that choline chloride based DESs may become promising neoteric solvents for peptide synthesis through biocatalysis. Copyright
Asymmetric transfer hydrogenation of prochiral carboxylic acids catalyzed by a five-coordinate Ru(II)-binap complex
Saburi,Ohnuki,Ogasawara,Takahashi,Uchida
, p. 5783 - 5786 (1992)
Asymmetric transfer hydrogenation of representative prochiral carboxylic acids was performed, using [RuH((S)-binap2]PF6 or a related complex as a catalyst and 2-propanol or ethanol as a hydrogen source, to achieve good to excellent enantioselectivities.
BIOCATALYTICAL TRANSFORMATIONS II. ENANTIOSELECTIVE HYDROLYSIS OF N-ACETYL-FLUORO-PHENYLALANINE-ETHYLESTERS BY LYOPHILISED YEAST
Csuk, Rene,Glaenzer, Brigitte I.
, p. 99 - 106 (1988)
The three nuclear substituted monofluoro D-N-acetylphenylalanine-ethylesters were obtained in excellent yield via enantioselective hydrolysis of their respective racemates by use of lyophilised yeast (Saccharomyces cerevisiae Hansen).
Novel chiral dendritic diphosphine ligands for Rh(I)-catalyzed asymmetric hydrogenation: Remarkable structural effects on catalytic properties
Yi, Bing,Fan, Qing-Hua,Deng, Guo-Jun,Li, Yue-Ming,Qiu, Li-Qin,Chan, Albert S. C.
, p. 1361 - 1364 (2004)
A series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of pyrphos 2 with Frechet-type polyether dendron 3. The relationship between the primary structure of the dendrimer and its catalytic properties was established in the Rh-catalyzed asymmetric hydrogenation of α-acetamido cinnamic acid 4. A remarkable structural effect on catalytic activity was observed.
Novel phosphine-phosphite and phosphine-phosphinite ligands for highly enantioselective asymmetric hydrogenation
Yan, Yongjun,Chi, Yongxiang,Zhang, Xumu
, p. 2173 - 2175 (2004)
Two novel phosphine-phosphite (S,R)-o-BINAPHOS and phosphine-phosphinite (S)-o-BIPNITE ligands based on ortho phenyl substituted (S)-BINOL have been synthesized. Extremely high enantioselectivity (over 99% ee in most cases) has been achieved for the Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives.
The effect of enzymatic reaction on dissolution rate: Theoretical analysis and experimental test
Johnson,Amidon
, p. 195 - 203 (1986)
The dissolution behavior of N-acetylphenylalanine ethyl ester (1) and N-benzoyltyrosine ethyl ester (2) from a rotating disk into aqueous solutions containing the enzyme α-chymotrypsin was investigated. The effect of the bulk enzymatic reaction on the dissolution rates is modeled using the continuity equation where the reaction term is considered a constant throughout the reaction zone. Dimensional analysis on the continuity equation defines the important parameter R* = K(cat)E0h2/(C(s)D) which is the ratio of the diffusion time to the reaction time. This parameter correctly predicted the fact that the enzymatic reaction had only a slight impact on the dissolution of the highly soluble 1 while the effect on the less soluble 2 was large. Also predicted by R* is the dissolution dependence on the catalytic rate constant. The variation of this rate constant with pH is consistent with the dependence on pH found for the dissolution rate of 2. It is further demonstrated that the decrease in dissolution rate with solubility can be significantly reduced when the dissolving compound is an enzyme substrate. For the two compounds used in this study the dissolution rate decreased with the square root of solubility, as predicted by the theoretical analysis in the presence of enzyme. Other experiments included the variation of the enzyme concentration and the rotational speed on the spinning disk. All experiments were designed to show how R* could correctly predict the relative importance of the convective, diffusive, and reactive processes.
From batch to flow processing: Racemization of N-acetylamino acids under microwave heating
Dressen, Mark H. C. L.,Van De Kruijs, Bastiaan H. P.,Meuldijk, Jan,Vekemans, Jef A. J. M.,Hulshof, Lumbertus A.
, p. 888 - 895 (2009)
The racemization of N-acetylindoline-2-carboxylic acid in P-xylene revealed beneficial rate enhancements due to microwave effects, by comparing conventional and microwave heating. The magnitude of this effect was governed by the degree of heterogeneity of the reaction system. The amount of catalyst, the temperature and the amount of cosolvent played a decisive role. The microwave effect completely vanished when a homogeneous solution was heated. During the microwave-assisted heterogeneous racemization of N-acetylphenylalanine in P-xylene a comparable microwave effect was observed. The microwave effects could be rationalized by adapting selective heating in the phase boundary region of solid and liquid. Additionally, a straightforward translation was achieved from batchwise operation in a stirred reactor to a batch-loop reactor. The (heterogeneous) racemization of N-acetylindoline-2-carboxylic acid retained its microwave effect in the loop reactor. Our results demonstrated that avoiding plugging of the tubular reactor is a severe challenge in scaling up.
