新型含2,4-咪唑啉二酮的4-甲基-3-苯基-2-酰亚胺噻唑啉的合成及生物活性

通过酰氯制备异硫氰酸酯,与5-(4-氨基苄基)-2,4-咪唑啉二酮反应合成了含2,4-咪唑啉二酮的N-苯甲酰基-N'-苯基硫脲,然后在三乙胺存在下再与溴丙酮发生碱催化缩合反应以中等以上收率合成了新型含2,4-咪唑啉二酮的4-甲基-3-苯基-2-酰亚胺噻唑啉,它们的化学结构经1H NMR,IR,HR-ESI-MS和化合物3g和4g的X-ray单晶衍射表征,硫脲与溴丙酮的反应机理通过化合物3g和4g的晶体结构得到进一步确证.初步生物活性测定结果表明:部分目标化合物对供试昆虫及菌种显现出良好的抑制活性,如在200 mg/L浓度下化合物3i和4q对小菜蛾的死亡率分别为86%和100%,在50 mg/L浓度下化合物4n对油菜菌核菌的抑制率为82.6%,而它们对油菜和稗草显示出微弱但并不特征的除草活性.     

(S)-(4-溴-2-甲苯)(3-甲基吗啉)甲酮的合成

以(S)-2-氨基丙醇和氯乙酰氯为起始原料,经酰化和环合反应制得(S)-5-甲基吗啉-3-酮（4）; 4经还原制得(S)-3-甲基吗啉(5); 5与4-溴-2-甲基苯甲酸酰化缩合合成了(S)-(4-溴2-甲基苯基)(3-甲基吗啉)-甲酮,总收率57%,其结构经¹H NMR 和 ¹³C NMR确证。     

2-烷硫基-5-苯基亚甲基-4H-咪唑啉-4-酮的合成与表征

用2-硫代-3-正丁基-5-苯基亚甲基4-咪唑啉二酮的-S-烷基化反应合成了2-烷硫基-3-正丁基-5-苯基亚甲基-4H-咪唑啉-4-酮衍生物。探讨了S-烷基化反应的反应条件和所合成化合物的波谱性质。目标产物均为新的化合物，其结构经元素分析，IR，1H NMR和MS确正。     

2-硫代-3-烷基-5-苯基亚甲基-4-咪唑啉二酮衍生物的有效合成新方法

应用烯基膦亚胺与二硫化碳、一级脂肪胺的串联aza-Wittig反应合成了2-硫代-3-烷基-5-苯基亚甲基-4-咪唑啉二酮衍生物。提出了可能的环化反应机理，探讨了所合成化合物的成环反应条件和波谱性质。经元素分析、IR,1H NMR和MS确证产物均为新化合物。     

5-(4-羟基苯基)-2,4-咪唑啉二酮酯类化合物的合成及其生物活性

在模拟AdSS酶天然抑制剂结构合成5-(4-羟基苄基)-2,4-咪唑啉二酮酯系列化合物的基础上,为优化其结构,以5-(4-羟基苯基)-2,4-咪唑啉二酮为中间体,合成了28个未见文献报道的5-(4-羟基苯基)-2,4-咪唑啉二酮羧酸酯类化合物,它们的结构均经IR,1HNMR和元素分析表征.初步生物活性测试表明目标化合物5-(4-羟基苯基)-2,4-咪唑啉二酮对叔丁基苯甲酸酯(2i)和2-噻吩酸酯(3b)在浓度200μg/mL时对拟南芥生长抑制率达70%..     

1,3-二甲基-2-咪唑啉酮的纯度测定

建立了一种简便、准确的测定1,3-二甲基-2-咪唑啉酮纯度的气相色谱分析方法,通过对反应过程中产物的跟踪测试,指导合成,使其产品纯度达到99.9%以上.     

2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4- 噻唑啉酮的合成

以2-氨基-5-取代苯氧甲基-1,3,4-噻二唑(1)为起始原料, 合成了中间体2-氯乙酰氨基-5-取代苯氧甲基-1,3,4-噻二唑)-2-乙酰亚胺(2)和2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-4-噻唑啉酮(3), 化合物3进一步与取代苯甲醛发生类Knoevenagle缩合反应, 得到了一系列2-(5-取代苯氧甲基-1,3,4-噻二唑-2-亚胺基)-5-(取代苯基亚甲基)-4-噻唑啉酮类化合物4a～4p. 目标化合物4a～4p的结构经IR, ¹H NMR和元素分析确证.     

2-(4-甲硫基苯氧基)－4H－咪唑啉-4-酮衍生物的合成及生物活性

咪唑啉酮;2-(4-甲硫基苯氧基)－4H－咪唑啉-4-酮衍生物的合成及生物活性     

2-苯基-4,5-二(4′-氨基苯基)咪唑的合成

以安息香为原料,经过乙酸酐酯化、乙酸铵噁唑环化、混酸硝化、液溴氧化开环合成了4,4′-二硝基苯偶酰(4);4在乙酸铵/冰乙酸体系中环化生成2-苯基-4,5-二(4′-硝基苯基)咪唑酰(5);5在三氯化铁存在下经水合肼还原制得2-苯基-4,5-二(4′-氨基苯基)咪唑,总收率63.2%,其结构经NMR,IR和元素分析表征。     

5-对甲氧基苯亚甲基咪唑啉-2,4-二酮的微波合成和晶体结构

标题化合物C11H10N2O3是由咪唑啉-2,4-二酮、对甲氧基苯甲醛在微波辐射下反应而得, 反应在5分钟内完成。结构通过单晶X-射线衍射法测定,其晶体属三斜晶系,空间群P, Mr = 218.21, a = 5.346(1), b = 10.212(2), c = 10.368(2) ? ?= 72.34(2), ?= 75.35(2), ?= 78.09(2), V = 516.6(2) ?, Z = 2, Dc = 1.403 g/cm3, = 0.104 mm-1, F(000) = 228, R = 0.0442, wR = 0.1152。咪唑环与苯环之间的两面角为5.45, 分子之间存在氢键, 形成了网状结构。     

High-performance liquid chromatographic determination of L-3-(3,4-dihydroxyphenyl)-2-methylalanine (alpha-methyldopa) in human urine and plasma

A procedure is described for the determination of alpha-methyldopa (MD) [L-3-(3,4-dihydroxyphenyl)-2-methylalanine], its metabolite and catecholamines in the urine and plasma of patients undergoing MD therapy, by high-performance liquid chromatography with dual working electrode coulometric detection. An efficient sample preparation procedure is presented for the isolation of endogenous MD, its metabolite and catecholamines from plasma or urine. After deproteinization of a plasma sample with methanol containing 2% of 0.5 M perchloric acid and dilution of a urine sample (1:200), MD, dihydroxyphenylacetic acid (DOPAC), 3-O-methylmethyldopa (3-OMMD) and homovanillic acid (HVA) were separated with a Supelcosil LC-18 column. Catecholamines were extracted from the supernatant of deproteinized plasma or from urine by ion exchange on a Sephadex CM-25 column and subsequent adsorption on alumina. The use of the same mobile phase for the concurrent assay of MD, its metabolite and catecholamines increased considerably the efficiency of sample separation. Recoveries were close to 100% for MD, DOPAC, 3-OMMD and HVA and 70% for catecholamines. The effects of various experimental parameters related to mobile phase composition on chromatographic performance are reported. The purity of the eluted compounds was tested by recording both the first detector response (oxidation current) and the second detector response (reduction current). The ratio of the detector responses yielded a chemical reversibility ratio for the detected compound. A number of applications such as monitoring data from patients under MD therapy are presented.     

Improved Preparation of (R) and (S)-3-Aminoquinuclidine Dihydrochloride

An improved procedure for the synthesis of either (R) or (S)-3-aminoquinuclidine was developed. Key intermediate imine 2 was made in a one pot process using lithium oxide as the base and molecular sieves.     

Synthesis,Configuration Judgment and Potentiation Activity of (2S,3S,E)-4-(3,4-Dihydroxybenzylidene)-3-(3,4-dihydroxyphenyl)-5-oxotetrahydrofuran-2-carboxylic Acid

The title compound(2S,3S,E)-4-(3,4-dihydroxybenzylidene)-3-(3,4-dihydroxyphenyl)-5-oxotetrahydrofuran-2-carboxylic acid was synthesized and the 2D structure was characterized by ~1H-NMR ~(13)C-NMR and LCMS. The absolute configuration was determined by single-crystal X-ray diffraction of the key intermediate(2S,3S,E)-ethyl 4-(3,4-dimethoxybenzylidene)-3-(3,4-dimethoxyphenyl)-5-oxotetrahydrofuran-2-carboxylate. The crystal belongs to tetragonal system, space group P4_1 with a = 13.0665(2), b = 13.0665(2), c = 13.4735(2) ?, V = 2300.4(6) ?~3, Z = 4, D_c = 1.278 g/cm~3, μ(CuKα) = 0.801 mm~(-1), F(000) = 936, S = 1.050, R = 0.0364 and wR(I 2σ(I)) = 0.1071. X-ray diffraction results showed that the molecular structure is stabilized totally by Van der Waals force. The antibacterial activity tests showed that the title compound possesses slight synergistic effect against MRSA and Acinetobacter baumanii.     

An Economical Large Scale Preparation of (2S,3S)-4,5-Dimethyl-2-Phenyl-L,3-Dioxolan

An economical 5-step synthesis of (2s,5s)-4,5-dimethyl-2-phenyl-l,3-dioxolan from (2R,3R)-tartaric acid is described.     

(2S,3S,4R)-2-正戊基-3,4-二叠氮基四氢噻吩的合成

以（＋）－4，10－二氧杂三环[5.2.1.O^2,6]－癸－8－烯－3－醇为原料。经8步反应，对映选择性地合成出去氧维生素H的重要中间体：（2S，3S，4R）－2－正戊基－3，4－二叠氮基四氢噻吩。为对映选择性合成手性四氢噻吩类化合物提供了新的方法。     

Stereoselective synthesis of (2R,3S,4S,5R)-trans-3,4-dihydroxy-5-(4-fluorophenoxymethyl)-2-(1-N-hydroxyureidyl-3-butyn-4-yl)tetrahydrofuran and (2R,3S,4S,5R)-trans-5-ethynyl-2-(4-fluorophenoxymethyl)-3,4-O-isopropylidene tetrahydrofuran from mannose diacetonide

Stereoselective synthesis of pharmaceutically interesting chiral tetrahydrofurans starting from mannose diacetonide is reported. A 1,4-diol system derived from mannose diacetonide, through a Mitsunobu reaction was stereospecifically cyclized to give chiral tetrahydrofurans. Both the C-1 and C-4 centers of d-mannose are successfully exploited to install the requisite side chains.     

Synthesis of N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine: An application of lanthanide-catalyzed transamidation

N-Fmoc-(2S,3S,4R)-3,4-dimethylglutamine (6) was synthesized from tert-butyl N-Boc-(2S,3S,4R)-dimethylpyroglutamate (13). This synthesis involved selective deprotection of a Boc group from a lactam nitrogen in the presence of a tert-butyl ester, Fmoc protection of the lactam, and a lanthanide-catalyzed transamidation reaction of the Fmoc-protected lactam, using ammonia and dimethylaluminum chloride. The scope of Lewis acid-catalyzed transamidation of acylated lactams was explored through the variation of lanthanide, lactam, acyl group, amine, and aluminum reagent. The reactivity of various metal triflates was found to vary in the following qualitative order: Yb approximately Sc > Er approximately Eu approximately Sm > Ce approximately Ag(I) > Cu(II) approximately Zn. Intriguingly, catalysis was only observed when ammonia was the nitrogen nucleophile; addition of other amidoaluminum complexes to acyl lactams was found to be insensitive to the addition of lanthanides.     

Preparation of dimethyl (R)- and (S)-2-(2-aminophenyl)-2-hydroxyethylphosphonate from anthranilic acid

An efficient synthesis of both enantiomers of dimethyl δ-amino-β-hydroxyethylphosphonate 6 has been achieved starting from anthranilic acid, through the resolution of dimethyl (±)-2-(2-N,N-dibenzylaminophenyl)-2-hydroxyethylphosphonate 9 with (S)-O-methylmandelic acid. The absolute configuration of the enantiomers 9 was assigned by the Dale and Mosher approach using the extended Newman projections and molecular mechanics.     

Synthesis of (2R, 3S, 4R)-2-Hydroxymethyl-3,4-Dihydroxypyrrolidine Hydrochloride from D-Glucose

(2R, 3S, 4R)-2-Hydroxymethyl-3,4-dihydroxypyrrolidine hydrochlo-ride was synthesized from diacetone-D-glucose.     

Improved Preparation of (E)-3-Trimethylsilyl-2-Buten-1-OL

An improved preparation of (E)-3-trimethylsilyl-2-buten-1-ol is described. The two-step process entails stereo-selective addition of (TMS)₂ CuLi-LiCN to ethyl tetrolate followed by reduction with diisobutylaluminum hydride and proceeds in 90% overall yield.