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Acid Intermediate (acid + intermediate)
Selected AbstractsThe mechanism of neutral amino acid decomposition in the gas phase.INTERNATIONAL JOURNAL OF CHEMICAL KINETICS, Issue 8 2001N -dimethylglycine, N -dimethylglycine ethyl ester, The elimination kinetics of N, ethyl 1-piperidineacetate The gas-phase elimination kinetics of the ethyl ester of two ,-amino acid type of molecules have been determined over the temperature range of 360,430°C and pressure range of 26,86 Torr. The reactions, in a static reaction system, are homogeneous and unimolecular and obey a first-order rate law. The rate coefficients are given by the following equations. For N,N-dimethylglycine ethyl ester: log k1(s,1) = (13.01 ± 3.70) , (202.3 ± 0.3)kJ mol,1 (2.303 RT),1 For ethyl 1-piperidineacetate: log k1(s,1) = (12.91 ± 0.31) , (204.4 ± 0.1)kJ mol,1 (2.303 RT),1 The decompositon of these esters leads to the formation of the corresponding ,-amino acid type of compound and ethylene. However, the amino acid intermediate, under the condition of the experiments, undergoes an extremely rapid decarboxylation process. Attempts to pyrolyze pure N,N-dimethylglycine, which is the intermediate of dimethylglycine ethyl ester pyrolysis, was possible at only two temperatures, 300 and 310°C. The products are trimethylamine and CO2. Assuming log A = 13.0 for a five-centered cyclic transition-state type of mechanism in gas-phase reactions, it gives the following expression: log k1(s,1) = (13.0) , (176.6)kJ mol,1 (2.303 RT),1. The mechanism of these ,-amino acids differs from the decarbonylation elimination of 2-substituted halo, hydroxy, alkoxy, phenoxy, and acetoxy carboxylic acids in the gas phase. © 2001 John Wiley & Sons, Inc. Int J Chem Kinet 33:465,471, 2001 [source] Stability and hydrolysis kinetics of spirosuccinimide type inhibitors of aldose reductase in aqueous solution and retardation of their hydrolysis by the target enzymeJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Masuo Kurono Abstract The stability and the hydrolysis kinetics of spirosuccinimide type aldose reductase (AR) inhibitors, SX-3030 (racemate) and its optical enantiomers (R - and S -isomers), were investigated in aqueous solution. The hydrolysis followed pseudo-first-order kinetics and showed significant pH dependence. Maximum solution stability was observed below pH 2.4, whereas the hydrolysis was gradually catalyzed by hydroxide ion at neutral to alkaline pH while the compounds exhibiting moderate pH-independent stability at acidic to neutral conditions (pH 4,7) to enable oral administration. A pK of 3.7 was obtained from the pH-rate profile, but this kinetically derived pK is approximately 2 pH units below the pK of the parent compounds, suggesting the presence of an acidic intermediate involved in the hydrolysis process. These findings, together with structural analysis, support the notion that the hydrolysis would proceed via nucleophilic attack of a water molecule or hydroxide ion on the scissile carbonyl bond of the succinimide ring to form a succinamic acid intermediate that has a ,-keto acid structure, followed by decarboxylation to give a racemized succinimide ring-opened product. On the other hand, the interconversion of the R - and S -isomers did not occur during hydrolysis; however, the hydrolysis of the R -isomer was markedly suppressed by the target enzyme AR whereas that of the S -isomer was not, indicating a high degree of complementarity of interacting surfaces between the R -isomer and the enzyme. The results in the present study could provide useful clues for facilitating the appropriate stabilization strategies as well as for evaluating the pharmacological effects on target tissues in vivo, and suggested that the R -isomer may be a suitable candidate as AR inhibitor. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1468,1483, 2008 [source] Theoretical study of the gas-phase decomposition of neutral ,-amino acid ethyl esters.JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 3 2003Elimination of ethyl picolinate, Part , ethyl 1-methylpipecolinate Abstract Theoretical studies of the thermolysis in the gas phase of two ,-amino acid ethyl esters, ethyl picolinate and ethyl 1-methylpipecolinate, were carried out using ab initio theoretical methods, at the MP2/6,31G(d) and MP2/6,311+G(2d,p) levels of theory. The reactions studied have two steps: the first corresponds to the formation of a neutral amino acid intermediate via a six-membered cyclic transition state, and the second is the rapid decarboxylation of this intermediate via a five-membered cyclic transition state. The progress of the first step of the reactions was followed by means of the Wiberg bond indices. The results indicate that the transition states have an intermediate character between reactants and products, and the calculated synchronicities show that the reactions are concerted and slightly asynchronous. The bond-breaking processes are more advanced than the bond-forming processes, indicating a bond deficiency in the transition states. The kinetic parameters calculated for both reactions agree very well with the available experimental results. Copyright © 2003 John Wiley & Sons, Ltd. [source] Asymmetric Synthesis of ,,,-Substituted ,-Sultones via Allylation of Chiral Lithiated SulfonatesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 20 2003Dieter Enders Abstract The first auxiliary controlled asymmetric synthesis of enantiopure ,,,-substituted ,-sultones via ,-allylation of lithiated sulfonates by using 1,2:5,6-di- O -isopropylidene-,- D -allofuranose as chiral auxiliary is described. The high asymmetric inductions of the ,-allylations were reached in good to excellent yields. Successive epimerization-free cleavage of the auxiliary and diastereoselective ring closure of the sulfonic acid intermediates in a one-pot procedure led to the title compounds in good to excellent yields and diastereo- and enantiomeric excesses (de, ee , 98%). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Bile acid treatment alters hepatic disease and bile acid transport in peroxisome-deficient PEX2 Zellweger mice,HEPATOLOGY, Issue 4 2007Megan H. Keane The marked deficiency of peroxisomal organelle assembly in the PEX2,/, mouse model for Zellweger syndrome provides a unique opportunity to developmentally and biochemically characterize hepatic disease progression and bile acid products. The postnatal survival of homozygous mutants enabled us to evaluate the response to bile acid replenishment in this disease state. PEX2 mutant liver has severe but transient intrahepatic cholestasis that abates in the early postnatal period and progresses to steatohepatitis by postnatal day 36. We confirmed the expected reduction of mature C24 bile acids, accumulation of C27,bile acid intermediates, and low total bile acid level in liver and bile from these mutant mice. Treating the PEX2,/, mice with bile acids prolonged postnatal survival, alleviated intrahepatic cholestasis and intestinal malabsorption, reduced C27,bile acid intermediate production, and prevented older mutants from developing severe steatohepatitis. However, this therapy exacerbated the degree of hepatic steatosis and worsened the already severe mitochondrial and cellular damage in peroxisome-deficient liver. Both untreated and bile acid,fed PEX2,/, mice accumulated high levels of predominantly unconjugated bile acids in plasma because of altered expression of hepatocyte bile acid transporters. Significant amounts of unconjugated bile acids were also found in the liver and bile of PEX2 mutants, indicating a generalized defect in bile acid conjugation. Conclusion: Peroxisome deficiency widely disturbs bile acid homeostasis and hepatic functioning in mice, and the high sensitivity of the peroxisome-deficient liver to bile acid toxicity limits the effectiveness of bile acid therapy for preventing hepatic disease. (HEPATOLOGY 2007;45:982,997.) [source] | ||||||||||