Synthesis and Antifungal Activities of New Type β‐Methoxyacrylate‐Based Strobilurin Analogues

Strobilurins have become one of the most important classes of agricultural fungicides. To discover new strobilurin derivatives with high activity against resistant pathogens, a series of novel β‐methoxyacrylate analogues were designed and synthesized by integrating substituted pyrimidine with a strobilurin pharmacophore. The compounds were confirmed and characterized by infrared, ¹H nuclear magnetic resonance, elemental analysis and mass spectroscopy. The bioassays indicated that most of the compounds 1 exhibited potent antifungal activity against Colletotrichum orbiculare, Botrytis cinerea Pers and Phytophthora capsici Leonian at the concentration of 50 μg/mL. Exhilaratingly, compound 1a (R=methyl) showed better antifungal activity against all the tested fungi than the commercial strobilurin fungicide azoxystrobin.     

N-{4-{N-甲基-N-[2-羟基-3-(2,4-二氧代-1,2,3,4-四氢嘧啶-5-基)氨基]丙基}氨基-3-溴}苯甲酰基-L-谷氨酸二乙酯及其衍生物的合成

报道了N-{4-{N-甲基-N-[2-羟基-3-(2,4-二氧代-1,2,3,4-四氢嘧啶-5-基)氨基]丙基}氨基-3-溴}苯甲酰基-L-谷氨酸二乙酯及其衍生物的简便合成方法. 分别以4-氨基苯甲酸乙酯和4-氨基苯甲酰基-L-谷氨酸二乙酯为起始物, 经甲基化、烯丙基化、溴羟基化、环氧化、开环、脱保护等反应首次合成了6个新型5-取代氨基嘧啶类化合物, 并通过¹H NMR, ¹³C NMR 和MS对其化学结构进行了表征. 初步生物活性结果表明, 苯环侧链的L-谷氨酸酯部分是此类化合物抑制人重组二氢叶酸还原酶的必需结构.     

Practical synthesis of bicyclic pyrazol-5-one derivatives

This communication describes a convenient synthesis of fused bicyclic pyrazolones in a one-pot reaction procedure. Modified protocols are also developed to access 5,5-bicyclic and bulky pyrazolones in good yields. The method reported herein represents a practical approach to structurally diversified bicyclic pyrazolones.     

Coupling Reaction of 4-Chloro-7-H-Pyrrolo[2,3-d]Pyrimidine with 2,3,5-Tri-O-Acetyl-β-D-Ribofuranosyl Chloride

Tubercidin (4-amino-7--D-riobofuranosyl-7-H-pyrrolo[2,3-d]pyrimidine) 1, an antibio-tic substance produced in the culture broth of Streptomyces tubericidus1, is an adenosine analog in which N-7 is replaced by a carbon atom. It has attracted much attention due to the biological activities for the growth inhibition of certain tumors, and many derivatives of tubercidin have been synthesized2-5.For the synthesis of tubercidin analogs, 4-chloro-7-H-pyrrolo[2,3-d]pyrimidine-2,3,5-tri-O-acetyl--D-r…     

Multi-component reactions between 2-aminopyrimidine, aldehydes and isonitriles: the use of a nonpolar solvent suppresses formation of multiple products

A reliable and convenient protocol for MCRs between 2-aminopyrimidine, aldehydes and isonitriles is described. Toluene was chosen as the reaction solvent based on mechanistic reasoning. The product mixtures were found to contain a single imidazo[1,2-a]pyrimidine product in each case, which were isolated and purified by precipitation and crystallization. Chromatographic recovery from filtrates raised the total yields to 49-66%. The procedure provides a practical alternative to hitherto reported methods in which formation of multiple products was observed.     

Synthesis of Hindered Phenolic Esters over Ion-Exchange Resins

The esterification of 3,5-di-tert-butyl-4-hydroxybenzoic acid with 1-hexadecanol over a series of ion-exchange resins was investigated, in which resin D072 exhibited excellent catalytic performance. The influence of water on the reaction was also investigated, and it was found that water could improve the selectivity and increase the yield of the target product. Treatment of resins with aqueous sodium hydroxide could improve the selectivity of the target product but remarkably decreased the conversion of 3,5-di-tert-butyl-4-hydroxybenzoic acid. This result indicated that strong Brønsted acid sites played an important role in the reaction. Furthermore, D072 was efficiently recycled four runs by simple treatment with mineral acid. Finally, a series of hindered phenolic esters were successfully synthesized under the optimal reaction conditions. Therefore, a simple and versatile method for the synthesis of hindered phenolic esters has been established over ion-exchange resins and the target products were obtained in good yields.     

2-(2-羟基苯亚甲基胺)-4,6-二羟基-嘧啶的质子转移异构化反应

为了探索2-(2-羟基苯亚甲基胺)-4,6-二羟基-嘧啶(M1)分子醇式和酮式结构互变异构化的反应机理,利用密度泛函理论(DFT)方法,在B3LYP/6-311+G(d,p)基组水平上,对M1化合物异构化反应的势能面进行了研究,在探讨各种可能的反应途径中,发现单体至少有8种异构体和10种过渡态.结果表明:2-(2-羟基苯亚甲基胺)-6-羟基-4(3H)嘧啶酮(M6)不论是单体、与水形成的配合物,还是二聚体,比其相对应的异构体能量低,表明在通常情况下是以M6形式稳定存在的;在考察的可能反应途径中,直接进行的分子内质子转移过程需要的活化自由能为143.8 kJ· mol-1,水助催化时,反应的活化自由能为38.9 kJ· mol-1,二聚体双质子转移的活化自由能为0.6 kJ·mol-1,二聚体双质子转移所需活化自由能最低,在室温下就可以进行,由此可见氢键在降低反应活化能方面起着重要的作用.     

Microwave-assisted synthesis of some novel fluorinated pyrazolo[3,4-d]pyrimidine derivatives containing 1,3,4-thiadiazole as potential antitumor agents

A facile microwave-assisted procedure for synthesis of novel fluorinated pyrazolo[3, 4-d]pyrimidine derivatives containing 1, 3, 4-thiadiazole is described. This protocol presented such advantages as short reaction time, high yields, simple purification and environmentally benign procedures. Their antitumor activities were evaluated against HL-60 by an MTT assay. The preliminary results indicated that some title compounds exhibit more potent antitumor inhibitory activity than doxorubicin (DOX).     

Computational Insights into Different Mechanisms for Ag-, Cu-, and Pd-Catalyzed Cyclopropanation of Alkenes and Sulfonyl Hydrazones

The [2+1] cycloaddition reaction of a metal carbene with an alkene can produce important cyclopropane products for synthetic intermediates, materials, and pharmaceutical applications. However, this reaction is often accompanied by side reactions, such as coupling and self-coupling, so that the yield of the cyclopropanation product of non-silver transition-metal carbenes and hindered alkenes is generally lower than 50 %. To solve this problem, the addition of a low concentration of diazo compound (decomposition of sulfonyl hydrazones) to alkenes catalyzed by either CuOAc or PdCl₂ was studied, but side reactions could still not be avoided. Interestingly, however, the yield of cyclopropanation products for such hindered alkenes were as high as 99 % with AgOTf as a catalyst. To explain this unexpected phenomenon, reaction pathways have been computed for four different catalysts by using DFT. By combining the results of these calculations with those obtained experimentally, it can be concluded that the efficiency of the silver catalyst is due to the barrierless concerted cycloaddition step and the kinetic inhibition of side reactions by a high concentration of alkene.     

萘基薁并[2,1-d]嘧啶-4-胺类衍生物的合成

研究了萘基薁并[2,1-d]嘧啶-4-胺类衍生物的合成方法.以托酚酮、萘乙酸乙酯、N,N-二甲基甲酰胺二甲缩醛(DMF-DMA)及芳香胺为原料,依次经过氯代、缩合、环加成、环化反应得到目标产物.该反应操作简单、条件温和、收率良好.产物的结构经1H NMR,IR及元素分析等得以证实.