Kinetic and thermodynamic analysis of the hydrolytic ring-opening of the malondialdehyde-deoxyguanosine adduct, 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)- pyrimido[1,2-alpha]purin-10(3H)-one

3-(2'-Deoxy-beta-D-erythro-pentofuranosyl)pyrimido[1,2-alpha]purin-10(3H)-one (M1dG) is the major reaction product of deoxyguanosine with malondialdehyde or base propenals. M1dG undergoes hydrolytic ring-opening to N2-oxopropenyl-deoxyguanosine (N2OPdG) under basic conditions. We report that ring-opening of M1dG as a nucleoside or in oligonucleotides is a reversible second-order reaction with hydroxide ion. NMR and UV analysis revealed N2OPdG(-) to be the only product of M1dG ring-opening in basic solution. The rate constant for reaction of M1dG with hydroxide is 3.8 M(-1) s(-1), and the equilibrium constant is calculated to be 2.1 +/- 0.3 x 10(4) M(-1) at 25 degrees C. Equilibrium constants determined by spectroscopic analysis of the reaction end-point or by thermodynamic analysis of rate constants determined over a range of temperatures yielded a value 2.5 +/- 0.2 x 10(4) M(-1). Kinetic analysis of ring-opening of M1dG in oligonucleotides indicated the rate constant for ring-opening is decreased 10-fold compared to that in the nucleoside. Flanking purines or pyrimidines did not significantly alter the rate constants for ring-opening, but purines flanking M1dG enhanced the rate constant for the reverse reaction. A mechanism is proposed for ring-opening of M1dG under basic conditions and a role is proposed for duplex DNA in accelerating the rate of ring-opening of M1dG at neutral pH.     

Synthesis of pyrimido[1,2-a]benzimidazoles from ethyl 2-ethoxymethylidene-3-oxo-3-(polyfluoroalkyl)propionates

Cyclization of ethyl 2-ethoxymethylidene-3-oxo-3-polyfluoroalkylpropionates with benzimidazol-2-amine in boiling 1,4-dioxane followed two concurrent pathways with participation of fluoroacyl and ethoxycarbonyl fragments and formation of, respectively, ethyl 4-hydroxy-4-polyfluoroalkyl-1,4-dihydropyrimido-[1,2-a]benzimidazole-3-carboxylates and 3-polyfluoroacylpyrimido[1,2-a]benzimidazol-4-ols. Dihydropyrimido[1,2-a]benzimidazole derivatives undergo dehydration to give ethyl 4-(polyfluoroalkyl)pyrimido[1,2-a]benzimidazole-3-carboxylates, whereas the hydroxy group in 3-polyfluoroacylpyrimido[1,2-a]benzimidazol-4-ols is capable of being replaced by the amino group of the second benzimidazole molecule with formation of 4-(1H-benzimidazol-2-ylamino)-3-polyfluoroacylpyrimido[1,2-a]benzimidazoles.     

反相高效液相色谱法测定N-{3-[3-(二甲基氨基)-1-氧基-2-丙烯基]-苯基}乙酰胺及其相关物质

N-{3-[3-(二甲基氨基)-1-氧基-2-丙烯基]-苯基}乙酰胺(NDAOPPAM)样品用流动相甲醇-水(38+62)混合溶液溶解,用DiamonsilC18色谱柱作固定相。在所述条件下,NDAOPPAM与合成反应中的反应物之一,3-乙酰氨基苯乙酮(AAMPAN)可完全分离。定量中用紫外光谱检测,波长为236nm,测得的峰面积值与NDAOPPAM浓度在40.4～161.6mg·mL-1范围内呈线性关系,检出限(3S/N)为1ng.L-1。测得方法的日内和日间相对标准偏差(n=6)依次为0.53%和0.89%。在NDAOPPAM产品中残留的未反应完的反应物AAMAPN可用同样方法测定。测得从不同批号产品取得的3个样品中AAMPAN的质量分数分别为0.32%,0.43%,0.49%。     

Kinetics and mechanism of base-catalyzed cleavage of some bicyclo[4.2.0.]octa-1,3,5-trien-7-one (benzocyclobuten-1(2H)-one) derivatives

The kinetics of cleavage of 3-hydroxybicyclo[4.2.0]octa-1,3,5-trien-7-ones in aqueous sodium hydroxide, and of the alkoxy and acetoxy analogues in methanolic sodium methoxide solution, were examined under pseudo-first-order reaction conditions. The dependence of the rate upon the basicity of the solvent, whether measured by H_? or by [OR^?], reflects the possible structure of the transition state. The deduced mechanism is also supported by the effects of substituents upon the reaction rate. The relative amounts of the volatile reaction products derived from o-toluic acid and from phenylacetic acid are understood in terms of the substituent effect upon the relative stabilities of the carbanions.     

The Synthesis of 3-(2'-Hydroxybutyl) isobenzofuran-1 (3H)-one

l（3H】．Isobenzoturans（Dhthalldes】werereDortedtoexhibitawiderangeofbiologicalactivities．Forexample,3－n－butylphthallde（NB）exhibitsantlasthmatlc’,antlconvuls－ant“actlvltles．PenEandZhouhavestudiedonthemetabolismofNBPInrats‘．Theyfoundthat...