N-(5-氯-2-羟苄基)氨基酸酯的合成、表征及抑菌活性

以5-Cl水杨醛和L-苯丙氨酸、L-亮氨酸及L-甘氨酸的脂肪酸酯为原料,通过碱催化的席夫碱缩合反应,合成了6种N-(5-氯-2-羟苄基)席夫碱氨基酸酯及其还原产物N-(5-氯-2-羟苄基)氨基酸酯。化合物的结构及组成经过IR、1HNMR和元素分析测试技术进行了表征。合成的席夫碱及其还原产物对革兰氏阴性菌、革兰氏阳性菌及真菌均有不同程度的抑制作用。质量分数为0.01%的N-(5-氯-2-羟苄基)席夫碱氨基酸酯对大肠杆菌的抑菌率达90%以上,而N-(5-氯-2-羟苄基)氨基酸酯对金黄色葡萄球菌的抑菌率也在90%以上,均为强抑菌活性,其中N-(5-氯-2-羟苄基)苯丙氨酸酯的抑菌率达98%以上。     

N-（5-氯-2-羟基苄基）氨基酸衍生物及其金属配合物的合成、表征及抑菌活性

以N-（5-氯-2-羟基苄基）氨基酸及其酯为配体,在室温下以水和甲醇为溶剂,采用分步法,以1∶1的摩尔比将配体与金属离子在弱碱性条件下混合,合成了20种未见报道的N-(5-氯-2-羟基苄基)氨基酸类金属配合物。 用核磁、红外和紫外光谱技术对其结构进行了表征。 证明在配合物中配体N-(5-氯-2-羟基苄基)氨基酸的羟基、胺基和羧基均参与了配位。 抑菌测试表明,N-(5-氯-2-羟基苄基)氨基酸类金属配合物的抑菌活性普遍高于其配体,尤其对白色念珠菌的抑菌效果更为明显,均高达100%。 对N-（5-氯-2-羟基苄基）席夫碱氨基酸酯的合成方法进行了优化,得到了较佳的合成工艺条件。     

卤代邻羟苄基谷氨酸(酯)的合成、表征及抑菌活性

分别用氯代水杨醛、溴代水杨醛与L-谷氨酸及其酯反应,首先制得水杨醛缩谷氨酸类席夫碱(2),再经硼氢化钠还原制得邻羟苄基取代谷氨酸及其酯(3),化合物的结构经IR、1H NMR、MS与元素分析表征确认. 测试表明,在质量浓度为0.05%时,卤代邻羟苄基谷氨酸对大肠杆菌具有高的抑菌活性,抑菌率高达97%,对白色念珠菌、金黄色葡萄球菌的抑菌效果较差,但其甲酯化产物卤代邻羟苄基谷氨酸甲酯对白色念珠菌具有高的抑菌活性,抑菌率高达100%,对大肠杆菌、金黄色葡萄球菌的抑菌效果较差,说明该类衍生物对菌株的抑杀作用具有明显的专一性和特异性,氯代邻羟苄基谷氨酸甲酯、溴代邻羟苄基谷氨酸甲酯是白色念珠菌的优良抗菌化合物。     

丙氨酸席夫碱Ni(Ⅱ)配合物法不对称合成α-甲基-(p-甲氧基)苯丙氨酸

以R-及S-2-[N-(N′-苄基)脯氨酰-氨基]-二苯甲酮的丙氨酸席夫碱Ni(Ⅱ)配合物和p-甲氧基苄基氯反应制备R-及S-α-甲基-(p-甲氧基)苯丙氨酸。探讨了碱对反应立体选择性的影响,确定了最佳反应条件: R-或S-2-[N-(N′-苄基)脯氨酰-氨基]-二苯甲酮的丙氨酸席夫碱Ni(Ⅱ)配合物与p-甲氧基苄基氯的摩尔比为1:1．1,反应时间2 h。R-及S-α-甲基-(p-甲氧基)苯丙氨酸的总收率分别为71．3％和70．9％,e．e．达97．5％,手性辅基2-[N-(N′-苄基)脯氨酰-氨基]．二苯甲酮的回收率为90％～95％。同时用核磁共振和旋光测试技术对产物进行了表征。     

3-(N-取代苯基-2-乙酰胺基)硫基-4-N-取代邻羟苯基亚胺基-5-甲基-1,2,4-三唑类化合物的合成及生物活性研究

以对称二氨基硫脲为原料,与冰醋酸反应生成5-甲基-4-氨基-1,2,4-三唑-3-硫酮(1);在弱酸性条件下,1与取代水杨醛反应生成席夫碱中间体5-甲基-4-(N-取代邻羟苯基)亚胺基-1,2,4-三唑-3-硫酮(2a～2c);最后在碱性条件下分别与N-取代苯基-2-氯乙酰胺发生烷基化反应生成15种未见报道的目标化合物3-(N-取代苯基-2-乙酰胺基)硫基-4-(N-取代邻羟苯基)亚胺基-5-甲基-1,2,4-三唑(3a～3o),其结构经IR,1H NMR,13C NMR确证.初步生物测试表明,质量分数为0.01%时,3a～3o对白色念珠菌的抑菌率均达90%以上,具有很强的抑菌活性;对金黄色葡萄球菌、大肠杆菌的抑菌率达80%以上,具有较强的抑菌活性.     

(S)-β-取代-α-氨基酸衍生物的不对称合成

以2-[N-(N'-苄基-L-脯氨酰)氨基]二苯甲酮的甘氨酸席夫碱Ni(Ⅱ)配合物为原料,经Aldol羟甲基化,脱水,Michael加成和水解反应及离子交换层析,合成了4个(S)-β-取代-α-氨基酸衍生物,产率60%~75%,ee值90%~95%,其结构经~1H NMR和元素分析确证。     

反-4-羟甲基哌啶-3-醇的合成

以4-羟甲基吡啶为原料,经苄基保护、硼氢化钠的还原、硼氢化氧化和脱苄基保护等四步反应得到新型5-羟色胺受体激动剂的关键中间体反-4-羟甲基哌啶-3-醇。总收率达55. 7%。产物结构经IR、1H NMR和MS分析确证,并对合成工艺进行了优化。     

N,N′-二（-2-羟苄基）取代咪唑烷的合成、表征及抑菌活性研究

利用生物活性叠加原理,将“邻羟苯基”和“咪唑烷”分子片断有机结合,合成了6种N,N′-二（-2-羟苄基）取代咪唑烷类化合物（3a-3f）.以水杨醛和乙二胺为起始原料,经缩合、NaBH4还原制得N,N′-二邻羟苄基乙二胺（2）,进而与芳醛类化合物缩合关环制得目标化合物. 化合物的结构经1H NMR、IR、MS和元素分析等表征确认.结果表明,水杨醛与乙二胺的缩合反应,可专一性地生成对称双缩席夫碱化合物（1）;芳醛上的取代基对缩合关环反应有显著影响,邻、对位吸电基可使芳醛的羰基活化,有利于缩合关环反应的进行,邻、对位供电基可使芳醛的羰基钝化,不利于缩合关环反应进行.抑菌测试表明,质量浓度为0.1%时,N,N′-二（-2-羟苄基）取代咪唑烷化合物对不同菌株的抑菌活性具有明显的特异性,对白色念珠菌、大肠杆菌的抑菌率高达100%,是一类极具潜力的抗真菌、抗革兰氏阴性菌的化合物.     

(S)-4-苄基-2-噁唑烷酮的合成工艺改进

以L-苯丙氨酸为原料,经还原和关环反应合成了(S)-4-苄基-2-噁唑烷酮,总收率66%,其结构经1HNMR,13C NMR和HR-MS表征。     

Boc-L-(苯丙)噻唑-4-甲酸甲酯的合成研究

本文分别以L-苯丙氨酸甲酯盐酸盐和叔丁氧羰基保护的L-苯丙氨酸为起始原料,经两种不同的合成路线,完成了Boc-L-(苯丙)噻唑-4-甲酸甲酯的合成。其中,第一条路线共五步反应,总收率18%;第二条路线共四步反应,总收率22%,两条路线所涉及的官能团转换和反应有:氨基Boc保护、酯基还原、羟基Parikh-Doering氧化,MnO_2氧化,N-甲氧基-N-甲酰胺化。     

1,6- and 1,7-naphthyridines. II. Synthesis from acyclic precursors

A number of 8-hydroxy-6-methyl-1,6-naphthyridin-5(6H)-one-7-carboxylic acid alkyl esters 3 and the isomeric 5-hydroxy-7-methyl-1,7-naphthyridin-8(7H)-one-6-carboxylic acid alkyl esters 4 were synthesized from acyclic precursors obtained starting from quinolinic anhydride 5. Thus, methanolysis of 5 afforded the hemiester 6 which treated with oxalyl chloride and sarcosine ethyl ester gave 3-(N-ethoxycarbonylmethyl-N-methylcarbamoyl)pyridine-2-carboxylic acid methyl ester 8. Compound 8 was cyclized to naphthyridines 3a-e with sodium alkoxides. The isomeric naphthyridines 4a-c were obtained by cyclization of the open intermediary 2-(N-ethoxycarbonylmethyl-N-methylcarbamoyl)pyridine-3-carboxylic acid methyl ester 9 obtained by a route that involves treatment of 5 with sarcosine ethyl ester and esterification with diazomethane. Spectroscopic properties (¹H nmr, uv, ir) of compounds 3 and 4 are discussed and confirmed the proposed structures.     

Synthesis,Antibacterial and Anthelmintic Activity of Novel 3-(3-Pyridyl)-oxazolidinone-5-methyl Ester Derivatives

In this study, a series of 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives was synthesized and characterized by ¹H NMR, ¹³C NMR, and LC-MS. The conducted screening antibacterial studies of the new 3-(3-pyridyl)-oxazolidone-5-methyl ester derivatives established that the methyl sulfonic acid esters have broad activity spectrum towards Staphylococcus aureus, Streptococcus pneumoniae, Bacillus subtilis and Staphylococcus epidermidis. Among them, compound 12e has the most potent activity, with an MIC of 16 μg/mL against B.subtilis, and could reduce the instantaneous growth rate of bacteria. Furthermore, molecular docking studies were also simulated for compound 12e to predict the specific binding mode of this compound. In addition, anthelmintic activity of these compounds was also evaluated against adult Indian earthworms (Pheretima posthuman). The results showed that compound 11b had the best effect. These results above can provide experimental reference for the development of novel antibacterial and anthelmintic drugs.     

Solvent Effects on the Protonation Constants of Some <Emphasis Type="Italic">α</Emphasis>-Amino Acid Esters in 1,4-Dioxane–Water Mixtures

The stoichiometric protonation constants of some α-amino acid esters (glycine methyl ester, glycine t-butyl ester, l-valine methyl ester, l-valine ethyl ester, l-valine t-butyl ester, l-serine methyl ester, l-serine ethyl ester, l-leucine methyl ester, l-leucine ethyl ester, l-leucine t-butyl ester, l-alanine methyl ester, l-alanine benzyl ester, l-phenylalanine methyl ester, l-phenylalanine ethyl ester, and l-phenylalanine t-butyl ester) in water and 20%, 40%, and 60% (v/v) 1,4-dioxane–water mixtures have been determined at an ionic strength of 0.10 mol⋅L⁻¹ NaCl and at 25.0±0.1 °C under a nitrogen atmosphere. A potentiometric method was used and the calculation of the protonation constants has been carried out using the BEST computer program. The results were discussed in terms of macroscopic properties of the mixed solvent. The stoichiometric protonation constants were influenced by changes in solvent composition and their variations were discussed in terms of preferential solvation. Also, knowledge the protonation constant of α-amino acid esters will be helpful when determining the microscopic equilibrium constants of their corresponding amino acids.     

Synthesis and antimicrobial activity of some netropsin analogues

Nine novel lexitropsins were synthesized by linking two netropsin-like moieties through three different dicarboxylic acids; 9,10-dihydro-2,7-phenanthrenedicarboxylic acid; [(3-[[(carboxymethyl)amino]carbonyl]benzoyl)amino]acetic acid and indole-2,5-dicarboxylic acid. The netropsin residues were modified by the use of N-isopentylpyrrole, 5-methylthiophene or 5-isopropylthiazole heterocyclic building blocks in place of the usual N-methylpyrrole. The compounds were tested against five gram-positive bacteria: Staphylococcus aureus, Streptomyces faecalis, methicillin resistant Staphylococcus aureus, Enterobacter cloacae, Mycobacterium fortuitum, three gram-negative bacteria: Klebsiella aerogenes, Proteus vulgaris, Escherichia coli and three fungi: Aspergillus niger, Candida albicans and Aspergillus nidulans. Some of the compounds showed significant inhibitory effects on the growth of the microorganisms.     

N-(溴代-2-吡咯甲酰基)氨基酸甲酯的合成

在室温条件下, 2-三氯乙酰基吡咯经溴代反应, 再与氨基酸甲酯反应得到一系列N-(溴代-2-吡咯甲酰基)氨基酸甲酯, 收率为64.8%～92.2%. 通过元素分析, ¹H NMR, IR和MS对产物结构进行了表征, 培养了N-(1-甲基-4,5-二溴-2-吡咯甲酰基)甘氨酸甲酯的单晶并进行单晶X射线衍射分析. 初步活性试验表明, 目标产物对金黄色葡萄球菌、粪链球菌等五种细菌有一定的抑制作用.     

Use of Diphenyliodonium Bromide in the Synthesis of Some N-Phenyl α-Amino Acids

The N-phenyl methyl esters 4 of glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, proline, serine, threonine, tyrosine, aspartic acid, and glutamic acid have been synthesized in good to excellent yields using diphenyliodonium bromide, AgNO₃, and a catalytic amount of CuBr starting from the relevant amino acid ester. The chiral integrity of the amino acids 5 was maintained during these reactions, which were confirmed by the synthesis of dipeptide for each N-phenyl amino acid. The structures of the new compounds were confirmed by the analysis of their IR, ¹H, and ¹³C NMR spectra in addition to CHN microanalysis or high-resolution mass spectrometry for the new N-phenyl amino acids 5 and the esters 4.     

Thermochemistry of methyl and ethyl esters from vegetable oils

This paper deals with the gas‐phase thermodynamic properties of methyl ester and ethyl ester of vegetable oils (fatty acid methyl esters and fatty acid ethyl esters respectively) present in biodiesel. The standard enthalpies of formation at 298.15 K, heat capacities, and entropies in the temperature range 300–5000 K are determined by means of quantum chemistry calculations along with a protocol developed for these compounds. The resultant data, currently not available in the literature for most of them, are critical to the modeling of combustion chemistry of the subject compounds. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 481–491, 2007     

Thiazolecarboxylic Acid Derivatives. 1. N-Substituted 2-Amino-4-methylthiazole-5-carboxylic Acid Derivatives

Acylation of the ethyl ester and anilide of 2-amino-4-methylthiazole-5-carboxylic acid gave 2-acetyl(arylsulfonyl)amino derivatives. Methylation of acetylaminothiazole and subsequent deacetylation gave 2-methylamino-4-methylthiazole-5-carboxylic acid, which was then converted into esters. The ethyl ester and anilide of thiazole-2-carboxylic acid were used as starting compounds for the synthesis of 2-dimethylaminoformimino- and 2-chlorobenzenesulfonylureido derivatives.     

糖基修饰的氨基酸类化合物的合成

通过对5种氨基酸酯化和氨基保护得到苄氧羰基氨基酸甲酯, 经肼解制备苄氧羰基氨基酸酰肼, 然后分别与3种不同的糖基异硫氰酸酯反应, 制备了相应的目标化合物15个, 且产率均在60%以上. 所有新化合物均经元素分析, IR, MS和¹H NMR确证. 同时探索了苄氧羰基氨基酸甲酯肼解的最佳反应条件.