含1,2,3-三氮唑结构的1,5-苯并硫氮杂?的合成及其抑真菌活性

设计合成了三类含1,2,3-三氮唑结构的1,5-苯并硫氮杂?化合物3-(1H-1,2,3-三氮唑)-4-芳基-2,5-二氢-1,5-苯并硫氮杂?(5a～5f)、3-(2H-1,2,3-三氮唑)-4-芳基-2,3-二氢-1,5-苯并硫氮杂?(6a～6f)和3-(1H-1,2,3-三氮唑)-4-芳基-2,3,4,5-四氢-1,5-苯并硫氮杂?(7a～7f).研究了中间体及目标产物的合成条件,分离出其中两个副产物并进行了结构确定.目标产物的抑真菌活性测试表明,化合物5a～5f对真菌具有良好的抑制作用,对新生隐球菌的抑制效果尤为突出.初步抑真菌构效关系研究表明, 1H-1,2,3-三氮唑环和C=C双键是化合物5a～5f抑真菌活性的关键官能团.     

C(3)-1,2,4-三氮唑取代的1,5-苯并硫氮杂■的合成及抑菌活性

设计合成了3类C(3)-1,2,4-三氮唑取代的1,5-苯并硫氮杂■化合物,2,3-二氢/2,5-二氢/2,3,4,5-四氢-3-(1,2,4-三氮唑)-4-芳基-1,5-苯并硫氮杂■.研究了中间体及目标产物的合成条件,确定了其中2个副产物的结构.目标产物的抑菌活性测试表明,2,3-二氢/2,5-二氢-3-(1,2,4-三氮唑)-4-芳基-1,5-苯并硫氮杂■对新生隐球菌和白色念珠菌表现出很高的抑制作用,在200μg/disc的浓度下,有4个化合物对新生隐球菌的抑制作用高于对照药物氟康唑,有3个化合物对白色念珠菌的抑制活性高于对照药物氟康唑.初步抑真菌构效关系研究表明,1,2,4-三氮唑环和C=N双键是2,3-二氢-3-(1,2,4-三氮唑)-4-芳基-1,5-苯并硫氮杂■抑真菌活性的关键药效团.     

1,5-苯并硫氮杂(艹卓)-α-苯基-β-内酰胺的合成、结构及谱学性质

苯并硫氮杂(艹卓)是一类具有多种生理活性的七元杂环化合物,近年来,其各类衍生物的合成及性质的研究受到人们的关注[1～5].我们曾用氯乙酰氯与1,5-苯并硫氮杂(艹卓)反应合成了具有两个活性结构单元的1,5-苯并硫氮杂(艹卓)-β-内酰胺衍生物,并发现其产物具有确定的构型[6].为了研究可能具有更好生理活性的α-烃基-β-内酰胺的杂(艹卓)衍生物,我们合成了4个新的苯基取代的杂(艹卓)衍生物(Ⅱa-Ⅱd),研究了它们的谱学特征和立体结构.     

新型含1,2,3-三唑基[1,2,4](噁)二唑并[4,5-a][1,5]苯并硫氮杂卓化合物的合成

将1,2,3-三唑环结构及1,2,4-噁二唑环等多个药效团结构叠加到同一个硫氮杂卓分子中,为药理及生理活性研究提供较好的先导化合物.反应在三乙胺存在下,用2,4-二芳基-2,3-二氢-1,5-苯并硫氮杂卓与α-氯代-2-苯基-1,2,3-三唑基-4-甲醛肟在室温进行1,3-偶极环加成反应,合成一系列的2-苯基-1,2,3-三唑基[1,2,4]噁二唑并[4,5-a][1,5]苯并硫氮杂卓化合物,并采用红外光谱、核磁共振、元素分析等测试技术对化合物进行了表征.     

C(2)-酰胺基-4-芳基-1,5-苯并硫氮杂的合成及抑菌活性的研究

设计合成了三类C(2)酰胺基取代的1,5-苯并硫氮杂衍生物:2-酰胺基(N-芳基)-4-芳基-1,5-苯并硫氮杂、2-酰胺基(N-烷基)-4-芳基-1,5-苯并硫氮杂和2-酰胺基(N,N-二烷基)-4-芳基-1,5-苯并硫氮杂,其结构用元素分析,IR,MS及1H NMR确证.测定了目标化合物的抑真菌活性,结果表明部分化合物对新生隐球菌具有中等强度的抑真菌活性.还研究了2-酰胺基-4-芳基-1,5-苯并硫氮杂的合成反应条件.     

新型含1,2,3-三唑基[1,2,4]噁二唑并[4,5-a][1,5]苯并硫氮杂卓化合物的合成

将1,2,3-三唑环结构及1,2,4-噁二唑环等多个药效团结构叠加到同一个硫氮杂卓分子中,为药理及生理活性研究提供较好的先导化合物。反应在三乙胺存在下,用2,4-二芳基－2,3－二氢－1,5-苯并硫氮杂卓与α-氯代-2－苯基－1,2,3-三唑基4－甲醛肟在室温进行1,3-偶极环加成反应,合成一系列的2－苯基－1,2,3-三唑基[1,2,4]噁二唑并[4,5－a][1,5]苯并硫氮杂卓化合物,并采用红外光谱、核磁共振、元素分析等测试技术对化合物进行了表征。     

2-烷氧羰基烷基/正丁基-4-芳基-1,5-苯并硫氮杂类化合物的合成及抑菌活性的研究

设计、合成了三类2位取代-1,5-苯并硫氮杂衍生物:2-烷氧羰基甲基-4-芳基-1,5-苯并硫氮杂、2-烷氧羰基乙基-4-芳基-1,5-苯并硫氮杂和2-正丙基-4-芳基-1,5-苯并硫氮杂.所有目标化合物结构经过元素分析,IR,MS,HRMS及1H NMR确证.研究了2-烷氧羰基烷基/正丁基-4-芳基-1,5-苯并硫氮杂的合成反应条件,测定了目标化合物的抑真菌活性.通过对该类化合物抑真菌活性的评价,进一步明确乙酯基在1,5-苯并硫氮杂1的生物活性中所起的作用.     

1,3-偶极环加成合成新型含2-苯基-1,2,3-三唑基-1,5-苯并硫氮杂(艹/卓)噁二唑并合衍生物

α,β-不饱和酮(1a～1e)与邻氨基苯硫酚反应, 得到含2-苯基-1,2,3-三唑基1,5-苯并硫氮杂(艹/卓)(2a～2e), 然后以此化合物为原料同1,3-偶极子氧化腈"现场"发生1,3-偶极环加成, 合成出一系列含2-苯基-1,2,3-三唑基的1,2,4-(口恶)二唑并合的1,5-苯并硫氮杂衍生物(3a～3j). 产物经元素分析、 IR、 1H NMR及MS加以确证.     

C(3)-酯基取代的1,5-苯并硫氮杂卓的合成、晶体结构及抑菌和构效关系的研究

设计、合成了三类C(3)酯基取代的1,5-苯并硫氮杂卓衍生物: 2,3/2,5-二氢和2,3,4,5-四氢-1,5-苯并硫氮杂卓-3-甲酸乙酯, 采用元素分析、IR、MS、1H NMR及X射线衍射法确定了标题化合物的分子结构．结构分析表明, 2,5-二氢-1,5-苯并硫氮杂卓-3-甲酸乙酯属单斜晶系, C2/c空间群, 晶胞参数为: a＝2.0319(4) nm, b＝1.4985(3) nm, c＝1.3659(3) nm, α＝90°, β＝120.49(3)°, γ＝90°, V＝3.5840(12) nm3, Z＝8, Dc＝1.397 g/cm3, μ＝0.351 mm－1, F(000)＝1560, R＝0.0478, Rw＝0.1304; 研究了2,3/2,5-二氢-1,5-苯并硫氮杂卓的合成反应条件, 发现该两种互变异构体分别是速度控制产物和平衡控制产物; 抑菌活性及抑真菌构效关系研究表明, 亚胺型的2,3-二氢-1,5-苯并硫氮杂卓具有明显的抑菌活性, 亚胺官能团是其抑真菌的药效团．     

微波作用下1,5-苯并硫氮杂(艹卓)-α-溴代-β-内酰胺衍生物的合成

1,5-苯并硫氮杂(艹卓)、溴乙酰氯在三乙胺的存在下,用微波辐射合成了5个新的1,5-苯并硫氮杂(艹卓)-α-溴代-β-内酰胺衍生物,并且还合成了已用常规方法合成出的9个1,5-苯并硫氮杂(艹卓)-β-内酰胺衍生物,对其结构进行了表征.文中研究了微波促进这类反应的最佳反应条件.     

Aminolysis of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>]1,3]thiazin-7-ones

We have established that the products of aminolysis of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo-[5,1-b][1,3]thiazin-7-ones in boiling ethanol are 3-R-3-(5-aryl-4H-1,2,4-triazol-3-ylsulfanyl)-propanamides, and at 180°C–210°C (depending on the structure of the substituent R): 3-phenyl-4,5-dihydro-1H-1,2,4-triazoline-5-thione and 3-arylacrylamides or 3-(3-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)propanamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1587–1592, October, 2005.     

Synthesis of 1H-1,2,3-triazole derivatives by the cyclization of aryl azides with 2-benzothiazolylacetonone, 1,3-benzo-thiazol-2-ylacetonitrile,and (4-aryl-1,3-thiazol-2-yl)acetonitriles

The cyclization of aryl azides with 2-benzothiazolylacetone, 1,3-benzothiazol-2-ylacetonitrile, and (4-aryl-1,3-thiazol-2-yl)acetonitriles in methanol in the presence of sodium methylate gives high yields of new products, 2-(5-methyl(amino)-1-aryl-1H-1,2,3-triazol-4-yl)-1,3-benzothiazoles and 1-aryl-(4-aryl-1,3-thiazol-2-yl)-1H-1,2,3-triazole-5-amines. 1,3-Benzothiazol-2-ylacetonitrile undergoes an anionic domino reaction with methyl 2-azidobenzoate or 2-azidobenzonitrile to give [1,2,3]triazolo[1,5-a]quinazoline derivatives. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 612–618, April, 2009.     

Reaction of 2,3-Dihydro-1,5-benzothiazepines and Phenylacetyl Chloride in the Presence of Triethylamine： A New Aspect on the Formation Mechanism of Dihydro-1,3-oxazin-4-one Derivatives

2a,4-Disubstituted 2,2a,3,4-tetrahydro-2-phenyl-1H-azeto[2,1-d][ 1,5]benzothiazepin-1-ones, as well as 2-substi-tuted 2,3-dihydro-3-phenylacetyl-2-styryl-benzothiazoles and 4a,6-disubstituted 3- .benzyl-4a,5-d/hydro-2-phenyl-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, were obtained from the reaction of 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepines with phenylacetyl chloride in the presence of triethylamine. The mechanism for the formation of 4a,5-dihydro-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, 2,3-dihydro-1,3-oxazin-4-one derivatives, was suggested.     

Synthesis and antimicrobial activity of 2,4-diaryl-2,3-dihydrobenzo[b][1,4]thiazepines

A new series of structurally diverse 2,3-dihydrobenzo[b][1,4]thiazepines (2,3-dihydro-1,5-benzothiazepines) with substituted phenyl groups at C(2) and C(4) have been synthesized by reaction of 3-(5-bromo-2-methoxyphenyl)-1-arylpropen-1-ones with 2-aminobenzenethiols. The structures of all the synthesized compounds were confirmed by their analytical and spectral data (IR, ¹H NMR, ¹³C NMR). All the synthesized compounds were evaluated for antibacterial and antifungal activity against a variety of bacterial and fungal strains and interesting results were obtained. Some of the compounds had antibacterial and antifungal activity comparable to that of ciprofloxacin and fluconazole.     

Azolyl-substituted 1,2,3-triazoles

Huisgen reaction of (E)-1,5-diarylpent-2-en-4-yn-1-ones and (E)-1,5-diarylpent-1-en-4-yn-3-ones afforded 1-aryl-3-(5-aryl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones and 3-aryl-1-(5-aryl-1H-1,2,3-triazol-4-yl)-prop-2-en-1-ones, respectively. (E)-1-Aryl-3-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-ones reacted with hydrazine hydrate and phenylhydrazine to give 72–93% of 4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles which underwent dehydrogenation on heating in boiling acetic acid with formation of the corresponding pyrazole derivatives. The molecular structures of (E)-3-phenyl-1-(5-phenyl-1H-1,2,3-triazol-4-yl)prop-2-en-1-one and 4-[3-(4-methylphenyl)-1-phenyl-4,5-dihydro-1H-pyrazol-5-yl]-5-phenyl-1H-1,2,3-triazole were studied by X-ray analysis. 4-(3-Aryl-4,5-dihydro-1H-pyrazol-5-yl)-5-phenyl-1H-1,2,3-triazoles showed toxicity against Daphnia magna.     

Chemistry of 2-methylene-2,3-dihydro-3-pyranones

5-Aryl-2-acylmethylene-2,3-dihydro-3-furanones are recyclized by the action of hydrazine hydrate with the formation of 3-substituted 6-aryl-1H-4-pyridazinones, 3-alkoxycarbonylacetyl-5-aryl-4-methylpyrazoles, or 5-aryl-3-(3-oxo-2,3-dihydro-1H-5-pyrazolyl) pyrazoles, depending on the structure of the starting materials and the ratio of the reactants. The last-named are also obtained by the hydrazinolysis of the known 2-alkoxycarbonylmethyl-2-hydroxy-1,5-diaryl-2,3-dihydro-3-pyrrolones.For Communication 6, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1031–1038, August, 1992.     

Exceptional isolation of both imine and enamine desmotropes of 4,1-benzothiazepines

The desmotropy of differently substituted (R∗)-3-ethoxycarbonyl-2-aryl-3,5-dihydro-4,1-benzothiazepines and 3-ethoxycarbonyl-2-aryl-1,5-dihydro-4,1-benzothiazepines was investigated. The target 4,1-benzothiazepines were obtained via the ring transformation of (2R∗,2aS∗)-2-chloro-2a-aryl-2,2a-dihydro-2H,4H-azeto[1,2-a][3,1]benzothiazin-1-ones with sodium ethoxide in ethanol. The β-amino ester intermediate of the ring-enlargement reaction was isolated. Surprisingly, the desmotropes obtained could be separated by column chromatography and proved to be unexpectedly stable in solution. Further comparative studies revealed the existence of only the enamine forms of regioisomeric 2-ethoxycarbonyl-3-aryl-4,5-dihydro-7,8-dimethoxy-1,4-benzothiazepine derivatives; in this case, no desmotropy occurred. The structures were proved by means of NMR and IR spectroscopy.     

Synthesis of 1-(1-aryl-1H-1,2,3-triazol-4-yl)-β-carboline derivatives

Reaction of 5-methyl-1-aryl-1H-1,2,3-triazole-4-carbocylic acid chlorides with tryptamine derivatives afforded substituted 1-aryl-N-[2-(1H-indol-3-yl)ethyl]-5-methyl-1H-1,2,3-triazole-4-carboxamides. At heating these compounds in toluene in the presence of POCl₃ and P₂O₅ Bischler-Napieralski cyclization occurs giving 1-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-4,9-dihydro-3H-β-carbolines that can be transformed into β-carboline and tetrahydro-β-carboline derivatives.