N-烷基-N-酰基磺酰胺聚苯乙烯基微球作为固相酰化剂的研究

一种可循环使用的固相试剂：N-烷基-N-酰基磺酰胺聚苯乙烯基微球(5), 通过对聚苯乙烯磺酰氯微球树脂进行两步功能基化的修饰反应来制备. 制备过程如下：聚苯磺酰氯树脂(1)与伯胺(2)反应得到聚苯乙烯基N-烷基磺酰胺树脂(3), 树脂3用酰氯(4)或酸酐酰化得到N-烷基-N-酰基磺酰胺聚苯乙烯基树脂(5). 酰化的树脂5作为酰基转移试剂与亲核试剂胺反应得到二级酰胺. 根据5上取代基对酰胺生成的程度的影响结果表明, 烷基R¹和酰基(R²CO)对酰基转移反应活性的大小依次分别为：苯基＞苄基＞甲基＞正丁基＞＞H和对硝基苯甲酰基(苯甲酰基＞乙酰基. 胺的亲核能力对酰胺的收率也有一定的影响. N-苯基-N-苯甲酰基磺酰胺树脂重复使用3次没有发现活性降低.     

含氨基酸席夫碱的5-氟尿嘧啶衍生物的合成及其抗肿瘤活性

以N 1-(2-四氢呋喃烷基)-5-氟尿嘧啶为原料, 与1,4-二溴丁烷反应, 得到N¹-(2-四氢呋喃烷基)-N³-(4-溴丁基)-5-氟尿嘧啶(2), 最后与氨基酸席夫碱的钾盐缩合, 得到13个新的目标化合物3. 其结构经IR, ¹H NMR, MS和元素分析确证. 初步的体外抗肿瘤试验结果表明, 目标化合物具有一定的抗肿瘤活性.     

二-吡啶氧基-轴向取代-四-α-(3-戊氧基)锡(IV)酞菁的合成与表征

以3-硝基邻苯二甲腈为起始原料, 与正戊醇反应合成3-戊氧基邻苯二甲腈(1), 然后在高温溶剂1-氯萘中经缩聚反应合成二氯-轴向取代-四-α-(3-戊氧基)锡酞菁(2), 2进一步与2-羟基吡啶在N,N-二甲基甲酰胺中合成二-吡啶氧基-轴向取代-四-α-(3-戊氧基)锡酞菁配合物3, 同时对相关化合物分别进行了元素分析, IR, ¹H NMR, UV/Vis, 荧光和质谱表征.     

穿心莲中两个黄酮苷的波谱学研究

研究了穿心莲中抗血栓的活性成分. 应用AB-8大孔吸附树脂、聚酰胺柱色谱及薄层色谱进行分离, 应用波谱学(¹H NMR, ¹³C NMR, DQFCOSY, TOCSY, HMQC, HMBC, NOESY等)方法进行结构鉴定. 分离得到两个黄酮苷类化合物, 确定了¹H NMR, ¹³C NMR信号的全归属. 化合物1鉴定为5,4'-二羟基-7-甲氧基黄酮-6-O-β-D-葡萄糖苷, 化合物2鉴定为5,4'-二羟基-7-甲氧基黄酮-8-O-β-D-葡萄糖苷, 化合物1为首次从该植物中分得, 首次对两个化合物的碳谱和氢谱进行了全归属.     

新型含环状α-羟基膦酸酯的N1-(四氢呋喃-2-基)-5-氟尿嘧啶衍生物的合成

通过N¹-(2-呋喃烷基)-N³-羟乙基-5-氟尿嘧啶的Moffatt氧化, 再与亚磷酸酯的加成反应合成得到8个新型含环状α-羟基膦酸酯的N¹-(四氢呋喃-2-基)-5-氟尿嘧啶衍生物, 采用IR, ¹H NMR, ³¹P NMR, MS和元素分析对其结构进行了表征.     

1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶的合成

报道了1,3-二(乙氧基甲基)-5-N,N-二甲氨基-6-甲基尿嘧啶方便、高产率的合成方法. 以6-甲基尿嘧啶(1)为起始物, 经硝化、嘧啶N¹,N ³-烷基化、还原及氨基甲基化, 首次高产率合成了1,3-二(乙氧基甲基)-5- N,N -二甲氨基-6-甲基尿嘧啶(5), 并对其化学结构进行了表征.     

槲树叶中的5种酚性成分

从槲树叶Quercus dentata Thunb中分离纯化得到五种酚性成分. 通过理化性质分析和光谱解析等手段确定其化学结构分别为: 2-新橙皮糖基-2,6-二羟基苯甲酸苯甲酯(1), 龙胆酸5-O-(6-O-没食子酰基)--D-吡喃葡萄糖苷(2), 3,5,7-三羟基色原酮-3-O--D-吡喃葡萄糖苷(3), 没食子酸(4), 儿茶素(5), 其中化合物1和3为新化合物.     

一步法合成N-1,3-二羟基丙烷-2-基烷基乙酰胺

以5-氨基烷基-2,2-二甲基-1,3-二噁烷为起始原料, 乙酸酐为酰化剂, 一步法选择性地合成氨基二醇类氨基乙酰化产物N-1,3-二羟基丙烷-2-基烷基乙酰胺. 该方法操作简便, 收率高. 所合成的4个新化合物的结构均经FTIR, ¹H NMR, ¹³C NMR及HRMS确证. N-3-(1,3-二羟基丙烷-2-基)丙基乙酰胺(1a)作为关键的中间体, 可以用于HIV-1 Tat/ PCAF BRD抑制剂4的合成.     

黄酮糖苷Parkinsonin B的全合成

天然黄酮碳糖苷化合物特有的稳定性和显著的生物活性, 使其化学合成成为当今糖化学领域的研究热点之一. 本工作立体专一性地全合成了天然黄酮碳苷Parkinsonin B. 通过控制物质的量比, 首先高选择性合成了2-羟基-4,6-二甲氧基苯乙酮(3), 并与糖给体O-(2,3,4,6-四-O-苄基-α-D-葡萄糖基)三氯乙酰亚胺酯(7)发生立体专一性糖基化反应得到碳糖苷化合物8, 化合物8经查耳酮路线进而合成黄酮碳苷Parkinsonin B (1). 经IR, MS, ¹H NMR及元素分析证实了产物及中间体的结构, 同时讨论了全合成反应的主要影响因素, 并对其¹H NMR解析进行了探讨.     

9-(β-D-2'-脱氧核糖基)-6-甲基嘌呤的合成

报道了9-(β-D-2'-脱氧核糖基)-6-甲基嘌呤合成的新方法. 以肌苷1为原料, 经酯化、氯化、氨解得6-氯嘌呤核苷(4), 再经过羟基保护、6-位甲基化反应及脱保护反应得到关键中间体6-甲基嘌呤核苷7, 用1,3-二氯-1,1,3,3-四异丙基二硅氧烷保护7核糖上的3,5-二羟基, 2-羟基与苯氧基硫代甲酰氯反应后得到9, 然后与氢化三正丁基锡[HSn(Bu-n)₃]还原脱氧, 最后脱保护得到目标化合物11. 产物结构经MS, ¹H NMR, 元素分析等鉴定.     

酰氨基硫脲及其相关杂环衍生物的研究III.1-(5-甲基异唑-3-甲酰基)-4-芳基氨基硫脲及其相关杂环衍生物

Eight 1-(5-methylisoxazol-3-ylcarbonyl)-4-substituted thiosemicarbazides (I), eight 3-(5-methylisoxazol-3-yl)-4-substituted-1,2,4-triazoline-5-thiones (II), seven 2-arylamino-5-(5-methylisoxazol-3-yl)-1,3,4-thiadiazoles, and five 2-arylamino-5-(5-methylisoxazol-3-yl)-1,3,4-oxadiazoles were prepared from isoxazole III and aryl isocyanates. The derivatives I and II showed antitubercular activity and promoted the growth of plumule of wheat in preliminary experiments     

Two new benzopyran derivatives from Gouania leptostachya DC. var. tonkinensis Pitard.

Two new benzopyran derivatives,1-[(rel 2S,3R)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]ethanone(1),and 1-[(rel 25,35)-3,5,7-trihydroxy-3,4-dihydro-2H-chromen-2-yl]ethanone(2),along with four known flavonoids,prodelphinidin C,prodelphinidin B3,(-)-epi-gallocatechin and(+)-gallocatechin,were isolated from the stems of Gouania leptostachya DC.var. tonkinensis Pitard.Their structures were determined on the basis of spectroscopic methods including HR-ESI-MS,1D and 2D NMR.Prodelphinidin C exhibited significant inhibitory activity forα-glucosidase.     

Synthesis and antioxidant evaluation of some new 2-benzoylamino-5-hetaryl-1,3,4-oxadiazoles

A series of new functionalized 2-benzoylamino-5-hetaryl-1,3,4-oxadiazoles were efficiently synthesized via the reaction of the versatile key intermediates, 2-benzoylamino-5-cyanomethyl-1,3,4-oxadiazole (1) and N-(5-(5-amino-3-phenylamino)-1H-pyrazol-4-yl)-1,3,4-oxadiazol-2-yl)-benzamide (13), with some appropriate electrophilic reagents. The structures of the newly synthesized compounds were established on the basis of elemental analyses, spectral data, and by alternative synthesis wherever possible. The mechanisms of the studied reactions are discussed. Also, we evaluate the antioxidant activity of some representative examples of the newly prepared compounds. Among the synthesized compounds, 2-benzoylamino-5-cyanomethyl-1,3,4-oxadiazole (1) and N-(5-(7-methyl-5-oxo-2-(phenylamino)-4,5-dihydropyrazolo[1,5-a]pyrimidin-3-yl)-1,3,4-oxadiazol-2-yl)benzamide (17) showed excellent antioxidant activity and exhibited high protection against DNA damage induced by the Bleomycin iron complex.     

1,3,4-噁二唑键联二芳基乙烯化合物的合成及性质

将1,3,4-噁二唑基团引入二芳基乙烯分子中, 合成了2种新的二芳基乙烯类光致变色化合物1-氰基-2-(2H-5-苯基-1,3,4-噁二唑)-1,2-二(2,4,5-三甲基-3-噻吩)乙烯(3)和1,4-二{[1-氰基-2-(2H-5-苯基-1,3,4-噁二唑)-1,2-二(2,4,5-三甲基-3-噻吩)乙烯]-1,3,4-噁二唑}苯(4). 通过IR, NMR, MS和元素分析对化合物进行了结构表征, 并研究了其UV-Vis吸收、荧光发射、动力学特性和抗疲劳性质. 实验结果表明, 化合物[STHZ]3[STBZ]和[STHZ]4[STBZ]具有良好的光致变色性质, 光致变色闭环反应为零级反应, 开环反应为一级反应.     

The use of umbelliferone in the synthesis of new heterocyclic compounds

New coumarin derivatives, namely 7-[(5-amino-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one, 5-[(2-oxo-2H-chromen-7-yloxy)methyl]-1,3,4-thiadiazol-2(3H)-one, 2-[2-(2-oxo-2H-chromen-7-yloxy)acetyl]-N-phenylhydrazinecarbothioamide, 7-[(5-(phenylamino)-1,3,4-thiadiazol-2-yl)methoxy]-2H-chromen-2-one and 7-[(5-mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)methoxy]-2H-chromen-2-one were prepared starting from the natural compound umbelliferone. The newly synthesized compounds were characterized by elemental analysis and spectral studies (IR, 1H-NMR and 13C-NMR).     

Syntheses of substituted 1-methyl-2-(1,3,4-thiadiazol-2-yl)-4-nitropyrroles and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-4-nitropyrroles

Starting from readily available ethyl-4-nitropyrrole-2-carboxylate ( 1 ), substituted 1-methyl-2-(1,3,4-thiadiazol-2-yl)-4-nitropyrroles and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-4-nitropyrroles were prepared. The reaction of 1 with diazomethane gave ethyl 1-methyl-4-nitropyrrole-2-carboxylate ( 2 ). Reaction of compound 2 with hydrazine hydrate afforded the corresponding hydrazide 3 . The reaction of 3 with formic acid yielded 1-(1-methyl-4-nitropyrrole-2-carboxyl)-2-(formyl)hydrazine ( 7 ). Refluxing of the latter with phosphorus pentasulfide in xylene yielded compound 6 in 40% yield. Reaction of compound 7 with phosphorus pentoxide afforded compound 9 . Reaction of compound 3 with 1,1′-carboxyldiimidazole in the presence of triethylamine yielded 2-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-oxadiazoline-4(H)-5-one ( 11 ). Refluxing compound 3 with cyanogen bromide in methanol gave compound 12 . Compound 13 could be obtained through the reaction of compound 3 with carbon disulfide in basic medium. Alkylation of compound 13 afforded the correspanding alkylthio derivative 14 . Reaction of 1-methyl-4-nitropyrrole-2-carboxylic acid ( 15 ) with thiosemicarbazide and phosphorus oxychloride gave 2-amino-5-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazole ( 16 ). Sandmeyer reaction of compound 16 yielded 2-chloro-5-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazole ( 17 ). Refluxing of the latter with thiourea afforded 2-(1-methyl-4-nitro-2-pyrrolyl)-1,3,4-thiadiazoline-4(H)-5-thione ( 18 ). Alkylation of compound 18 gave the corresponding alkylthio derivative 19 . Oxidation of the latter with hydrogen peroxide in acetic acid yielded 2-(1-methyl-4-nitro-2-pyrrolyl)-5-methylsulfonyl-1,3,4-thiadiazole ( 20 ).     

Nitroimidazoles. VI. Syntheses of 1-methyl-2-(1,3,4-thiadiazol-2-yl)-5-nitroimidazole and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-5-nitroimidazole

Starting from readily available 1-methyl-5-nitroimidazole-2-carboxylic acid hydrazide (1), 1-methyl-2-(1,3,4-thiadiazol-2-yl)-5-nitroimidazole (4) and 1-methyl-2-(1,3,4-oxadiazol-2-yl)-5-nitroimidazole (10) were prepared. The reaction of 1 with formic acid gave 1-(1-methyl-5-nitroimidazole-2-carboxyl)-2-(formyl)hydrazine ( 8 ) in high yield. Refluxing of the latter with phosphorus pentasulfide in xylene yielded compound 4 in 50% yield. Reaction of compound 8 with phosphorus pentoxide afforded compound 10 in 60% yield.     

1,3,4-噁二唑和1,3,4-噻二唑衍生物的设计、合成和生物活性研究

为了寻求新型抗肿瘤药物,设计并合成了一系列新型1,3,4-噁二唑和1,3,4-噻二唑衍生物,对这些化合物在人类四种癌细胞:B-16(皮肤黑色素瘤细胞)、PC-3(人前列腺癌细胞)、U87(人原发性胶质母细胞瘤细胞)和A549(人非小细胞肺癌细胞)进行抗肿瘤活性评价.结果显示部分化合物具有较好的抗肿瘤活性,尤其是5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(2-甲氧基苯基)酰胺(8b)]和5-{6-[4-(2-羟基乙基)哌嗪-1-基]-2-甲基嘧啶-4-基氨基}-[1,3,4-噻二唑-2-羧酸(4-甲氧基苯基)酰胺(8c)],对四种癌细胞都显示出较高的抗肿瘤活性,其抑制活性均优于阳性对照达沙替尼,随后对这类化合物抑制肿瘤的可能靶点开展了进一步研究.     

新型含哌嗪1,3,4-噻二唑酰胺衍生物的合成及其生物活性

以氨基硫脲和二硫化碳为起始原料,合成了15个新型的1,3,4-噻二唑衍生物(6a~6o),其结构经¹H NMR,¹³C NMR,IR,ESI-MS和元素分析表征。生物活性测试结果表明：大部分化合物对水稻白叶枯细菌有良好的抑制活性,其中,N-［5-(2,4-二氯苄基)硫醚］-1,3,4-噻二唑-2-(2-N-甲基哌嗪)-乙酰胺(6b)和N-［5-(4-三氟甲氧基苄基)硫醚］-1,3,4-噻二唑-2-(2-N-甲基哌嗪)-乙酰胺(6e)的EC₅₀分别为17.5 μg·mL^-1和19.8 μg·mL^-1; N-[5-(3-甲基苄基)硫醚)-1,3,4-噻二唑-2-(2-哌嗪)-乙酰胺(6k)在浓度为500 μg·mL^-1时,对烟草花叶病毒有一定的抑制活性。     

Reactions with Hydrazonoyl Halides 611: Synthesis of 2,3-Dihydro-1,3,4-Thiadiazoles

2-[1,2-Diaza-3-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))prop-2-enylidene]-3-phenyl-5-substituted 1,3,4-thiadiazolines and 2-{[4-(2,3-dimethyl-5-oxo-1-phenyl(3-pyrazolin-4-yl))(1,3-thiazol-2-yl)]cyanomethylene}-3-phenyl-5-substitu- ted 1,3,4-thiadiazolines were synthesized from hydrazonoyl halides and 4-{-2-aza-2-[(methylthiothioxomethyl)amino]vinyl}-2,3-dimethyl-1-phenyl-3-pyrazoin-5-one and 2-[4-(2,3-dimethyl-5-oxo-1-phenyl-3-pyrazolin-4-yl)-1,3-thiazol-2-yl]ethane-nitrile, respectively. All synthesize compounds were elucidated by elemental analysis, spectra, and alternative synthesis routes, whenever possible.