2-氯甲基-3-甲基-4-[(3-甲氧基)丙氧基]-吡啶盐酸盐的合成

以2,3-二甲基吡啶为原料,经6步反应合成了雷贝拉唑的关键中间体--2-氯甲基-3-甲基-4-[(3-甲氧基)丙氧基]-吡啶盐酸盐,总收率14.1%.     

新型1-吡啶基-3,5-二甲基-1-氢吡唑类化合物的合成及晶体结构

以卤代吡啶为起始原料与水合肼反应合成肼基吡啶衍生物中间体,该中间体进一步与2,4-戊二酮关环合成了一类新型1-吡啶基-3,5-二甲基吡唑衍生物。对合成目标化合物进行了质谱、核磁表征。并且采用X射线单晶衍射分析方法进一步测定了目标化合物1-(3,5,6-三氯吡啶-2-基)-3,5-二甲基-1氢吡唑(3f)的晶体结构。     

3,3-二甲基-1-(吡啶-3-基)-丁-2-酮肟酯的合成及抑菌活性

以3-甲基吡啶、特戊酸乙酯、盐酸羟胺和取代苯甲酸等为原料,经加成、肟化和酯化反应,合成了12种新型的3,3-二甲基(吡啶-3-基)-丁-2-酮肟酯.该方法反应条件比较温和、收率高.化合物的结构通过IR、~1H NMR、~(13)C NMR和元素分析确证.采用菌丝生长速率法测试了目标化合物对两种病原菌的离体抑制活性,O-(4-溴苯甲酰基)-3,3-二甲基-1-(吡啶-3-基)-丁-2-酮肟(3h)和O-(4-氯苯甲酰基)-3,3-二甲基-1-(吡啶-3-基)-丁-2-酮肟(3j)对菌核菌有较强的抑制活性,EC50值分别为5.07和4.81μg/mL;3h、3j和O-(3,4-二氯苯甲酰基)-3,3-二甲基-1-(吡啶-3-基)-丁-2-酮肟(3l)对灰霉菌显示出较高的抑制活性,EC50值分别为4.98、5.44和6.34μg/mL.     

2,6-双(3′-溴甲基-1′-吡唑基)-4-溴吡啶的合成与表征

以2,6-双(3′-甲基-1′-吡唑基)-4-氨基吡啶为原料,经重氮化,溴化合成了新型时间分辨荧光免疫分析双功能螯合剂中间体2,6-双(3′-溴甲基-1′-吡唑基)-4-溴吡啶.结构通过IR,MS,1H NMR和元素分析进行了表征,对合成条件进行了探讨.     

达比加群酯中间体3-【【【2-{[(4-氰基苯基)氨基]甲基}-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯的合成

以对氨基苯腈为起始原料,经胺化反应制得N-(4-氰基苯基)甘氨酸(4);4与N-[3-氨基-4-(甲基氨基)苯甲酰基]-N-2-吡啶-β-丙氨酸乙酯(5)经酰胺化后经闭环反应,合成了达比加群酯的关键中间体——3-【【【2-{[(4-氰基苯基)氨基]甲基}-1-甲基-1H-苯并咪唑-5-基】羰基】(吡啶-2-基)氨基】丙酸乙酯,总收率79.6%,其结构经~1H NMR和ESI-MS确证。     

3-(2-氯-4-三氟甲基苯氧基)苯甲酸酯的合成、晶体结构及生物活性

以3-(2-氯-4-三氟甲基苯氧基)苯甲酸为起始原料,经氯化亚砜氯化后得中间体3-(2-氯-4-三氟甲基苯氧基)苯甲酰氯(1),再与不同取代的苯酚反应,合成了13个未见文献报道的3-(2-氯-4-三氟甲基苯氧基)苯甲酸酯(2).通过1H NMR,IR,EI-MS和元素分析对所合成的化合物进行了结构表征,3-甲基苯基3-(2-氯-4-三氟甲基苯氧)苯甲酸酯(2f)通过单晶X射线衍射进一步确证结构.初步的除草活性测试结果表明:大多数目标化合物在1.5 kg/ha剂量下对双子叶植物油菜和苋菜具有较高的抑制活性.     

N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类新化合物的合成及生物活性

以N-吡啶基吡唑甲酸和2-氨基-3-甲基苯甲酸为起始原料,经由亲核加成、环化和酰化等多步反应合成了一系列结构新颖的N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)酰胺类化合物.测试了所合成化合物的杀虫及抑菌活性,结果表明,新化合物大多化合物在200 mg·L^-1浓度下对东方粘虫(Mythimna separataWalker)具有一定的杀虫活性,尤其是N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)乙酰胺(8a)和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3-氯-2,2-二甲基丙酰胺(8e)致死率可达70%;部分化合物在50 mg·L^-1浓度下对油菜菌核病菌的抑菌活性相对较好(54.5%~63.6%),优于triadimefon和chlorantraniliprole;部分化合物如N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-3,3-二甲基丁酰胺80和N-(2-(5-(3-溴-1-(3-氯吡啶-2-基)-1H-吡唑-5-基)-1,3,4-噁二唑-2-基)-4-氯-6-甲基苯基)-4-氟苯甲酰胺(8h)对苹果轮纹病菌具有中等抑菌活性.值得注意的是,化合物8e的杀粘虫活性和对油菜菌核病菌的抑菌活性都较为突出,可用作新农药创制研究的新型参考结构.     

2-氨基-5-氰基-N,3-二甲基苯甲酰胺合成方法改进

从3-甲基氨茴酸出发,用氯化亚砜取代光气及其衍生物,通过2种不同的反应途径,高收率地合成了氰虫酰胺的关键中间体2-氨基-5-氰基-N,3-二甲基苯甲酰胺(1)。考察了不同形态的甲胺、反应温度、溶剂以及不同的吡啶衍生物对反应的影响。     

2,6-双(3-甲基-1H-吡唑基)-4-氨基吡啶的合成与表征

以2,6-二溴吡啶为起始原料,经过氧化、硝化、还原、亲核取代等四步合成了新型时间分辨荧光免疫分析双功能螯合剂中间体2,6-双(3-甲基-1H-吡唑基)-4-氨基吡啶.化合物结构通过DSC,IR,气质联用色谱(GC-MS),1H NMR和元素分析等确证,对合成条件进行了探讨.     

4-取代-1-(2-甲基-6-(吡啶-3-基)-烟酰)氨基脲类衍生物合成与生物活性研究（英文）

经分子杂交技术合成了一系列4-取代-1-(2-甲基-6-(吡啶-3-基)-烟酰)氨基脲类衍生物.采用噻唑蓝(MTT)比色法研究了目标化合物对人肝癌细胞(QGY-7703)、人肺癌细胞(NCl-H460)和乳腺癌细胞(MCF-7)的体外抗肿瘤活性.1-(2-甲基-6-(吡啶-3-基)烟酰基)-4-(2,4,6-三氯苯基)氨基脲(4n)显示了最优的活性,其半数抑制浓度(IC_(50))为8.89～11.45μmol/L.细胞体内的生物研究显示,4n药物处理能明显增加细胞体内PARP切割水平以及诱导QGY-7703肿瘤细胞的凋亡.     

Reactions of chloromethoxy-substituted 3-(2-acetoxyethyl)-1-hydroxytriaz-1-ene 2-oxides with 1-alkoxy-3-(2-hydroxyethyl)triaz-1-ene 2-oxide alkali salts

Reactions of 1-alkoxy-3-(2-hydroxyethyl)triaz-1-ene 2-oxides and 1-chloromethoxytriaz1-ene 2-oxides with chloromethoxy derivatives of 3-alkyl-3-(2-acetoxyethyl)- and 3,3-bis(2-acetoxyethyl)-1-hydroxytriaz-1-ene 2-oxides result in very complex product mixtures with the major product comprising the starting salt fragments linked by a methylene bridge. In these products, the central methylene group bridges either two oxygen atoms or two nitrogen atoms, or one oxygen and one nitrogen atom. The synthesized compounds contain from two to four 2-hydroxyethyl moieties.     

Synthesis and reactions of some 3-(2-haloacyl)indoles

The reaction between indole and N-(2-haloacyl)pyridinium salts has been studied. With dioxan as solvent 1-(2-haloacyl)indole (2) was generally the product at low temperatures and 3-(2-haloacyl)indole (1) at high temperatures, as illustrated by the following α-bromopropionylation: Product ratio (1c/2a), 20° (0·01), 40° (0·8) and 60° (8·5). The fact that the a-bromobutyrylation at 60° gave 3-{N-(2-bromobutyryl)-1,4-dihydro-4-pyridyl}indole (6) as the main product, and 3-(2-bromobutyryl)indole (1d) only as a minor product, shows that the 3-acylation is affected by steric hindrance.At high reaction temperature (> 60°) the yield of1 decreased, owing to the formation of 3-indacylpyridinium salts (4).     

Hydrolysis Reactions and Resolution of (±)-2-Acetamido-3-hydroxy-1-(4-nitrophenyl)-1-propanone

IntroductionChloramphenicol,which was isolated fromStreptomyces venezuelae in 1 947[1] ,is used as abroad- spectrum antibiotic possessing activityagainst many Gram- negative and Gram- positivemicroorganisms. (± ) - 2 - Acetamido- 3 - hydroxy- 1 -(4- nitrophenyl) - 1 - propanone[(± ) - 1 ]is one of theintermediates of producing chloramphenicol.Petrow et al.[2 ] reported some transformations of(± ) - 1 in hydrolysis reactions. However,thereaction products were complicated under multiplehydr…     

采用通透性处理的安大略假丝酵母全细胞高效合成(R)-2-氯-1-(3-氯苯基)乙醇(英文)

考察了利用安大略假丝酵母(Candida ontarioensis)静息细胞不对称催化2-氯-1-(3-氯苯基)乙酮合成(R)-2-氯-1-(3-氯苯基)乙醇的转化反应条件.结果表明,当底物浓度为10g/L时,在最适转化条件下反应72h,产物的ee值和产率分别达到99.9%和99.0%.采用4g/L十六烷基三甲基溴化铵对Candida ontarioensis细胞于4℃通透性处理20min后,全细胞的酶活提高2倍以上.当底物浓度提高为30g/L,转化24h后,产物的ee和产率分别达到99.9%和97.5%.该研究为高效制备(R)-2-氯-1-(3-氯苯基)乙醇提供了可行途径,并为生物催化合成芳基手性醇类手性中间体提供了理论指导。     

(2E,4S)-4-叔丁氧羰基氨基-5-[(3S)-2'-氧代-3'-吡咯烷基]-2-戊烯酸乙酯的立体选择性合成及绝对构型

在(2E,4S)-4-叔丁氧羰基氨基-5-[(3S)-2'-氧代-3'-吡咯烷基]-2-戊烯酸乙酯(1)已有立体选择性合成路线的基础上,对各步产物的光学纯度进行了严格的检验,研究了反应条件对这些产物光学纯度的影响,并利用单晶X射线衍射方法确定了该类化合物的绝对构型.     

Synthesis of 1-(2-ethyl-3-indolyl)-1-(3-pyridyl)ethylene and related ellipticine analogues

Indole, 2-methylindole, and 3-etliylindole have been condensed with acetyl- and propionylpyridine, respectively. When propionylpyridine was used as the reactant, the product always was a 1-(pyridyl)-1-indoly[propylene. Condensation of 2-substituted indoles with 3-acetylpyridine gave similar products, whereas a similar condensation with 4-acetylpyridine gave 1,2-bis(3-indolyl)-1-(4-pyridyl)ethanes (e.g. 7a ). Condensation of unsubstituted indole with 3-or 4-acetylpyridine respectively, gave 1,1-bis(3-indolyl)-1-(pyridyl)ethanes (e.g. 6c ).     

Synthesis and some transformations of 2-(2-thienyl)-1(3)H-imidazo[4,5-f] quinoline

2-(2-Thienyl)-1(3)H-imidazo{cm[4,5-f]}quinoline was synthesized by the Weidenhagen reaction of quinoline-5,6-diamine with thiophene-2-carbaldehyde. Its methylation in the system KOH-DMSO gave isomeric 1-methyl-2-(2-thienyl)-1H- and 3-methyl-2-(2-thienyl)-3H-imidazo{cm[4,5-f]}quinolines, the latter being the major product. The 3-methyl derivative was subjected to electrophilic substitution reactions (bromination, nitration, formylation, acylation, sulfonation). Depending on the conditions, electrophilic attack was directed at the thiophene or quinoline fragment or both these.     

Biotransformation of (1S)-2-carene and (1S)-3-carene by Picea abies suspension culture

Biotransformation of (1S)-2-carene and (1S)-3-carene by Picea abies suspension culture led to the formation of oxygenated products. (1S)-2-Carene was transformed slowly and the final product was identified as (1S)-2-caren-4-one. On the other hand, the transformation of (1S)-3-carene was rapid and finally led to the formation of (1S)-3-caren-5-one and (1S)-2-caren-4-one as equally abundant major products. The time-course of the reaction indicates that some products abundant at the beginning of the reaction (e.g. (1S, 3S, 4R)-3,4-epoxycarane and (1R)-p-mentha-1(7),2-dien-8-ol) were consumed by a subsequent transformations. Thus, a precise selection of the biotransformation time may be used for a production of specific compounds.     

Synthesis of 3-(2-thienyl)alanine

Summary 3-(2-Thienyl)alanine was prepared by condensing 2-thiophenecarboxaldehyde with 2,5-piperazinedione, reducing the condensation product, and finally hydrolyzing the reduction product.     

Synthesis and Bioactivity of Novel Aminomethyl-2-（1, 2,4-triazol）-4, 4-dimethyl-3-pentanone （ol）

3, 3-Dimethyl-1-(1,2,4-triazol)-2-butanone was treated with aqueous formaldehyde to give an additional product, and subsequent elimination by acetic anhydride yielded 4,4-dimethyl-2-(1,2,4-triazol)-1-penten-3-one. Further addition with substituted amines provideda series of (1,2,4-triazol)-4,4-dimethyl-3-pentanone, which were then reduced by KBH4 to obtaina series of (1,2,4-triazol)-4,4-dimethyl-3-pentanol. Their structures were confirmed by ^1HNMR and elemental analysis. The results of bioassay showed that the title products possess good fungicidal activities.