异维A酸席夫碱酯的合成

以二环己基碳酰亚胺为脱水剂,4-二甲氨基吡啶为催化剂,异维A酸与对羟基苯胺发生酯化反应,生成异维A酸酯(1);1与醛反应,合成了4个异维A酸席夫碱酯,其结构经1H NMR和IR表征.     

4-羰基异维A酸(4-N-茄尼基氨基苯酚)酯的合成

以异维A酸和茄尼醇为原料,经氧化、溴化、酯化等一系列反应合成了4-羰基异维A酸(4-N-茄尼基氨基苯酚)酯,其结构经1H NMR,IR和MS表征。     

异维A酸4-氨基安替比林席夫碱酯的合成

以二环己基碳酰亚胺为脱水剂,4-二甲氨基吡啶为催化剂,异维A酸与甲酰基酚发生酯化反应生成了异维A酸酯(1a~1d);1再与4-氨基安替比林反应,合成了4个异维A酸4-氨基安替比林席夫碱酯(2a~2d)。2的结构由1HNMR,IR和MS确证。     

8-5′新木脂素类化合物的合成方法研究

对羟基桂皮酸甲酯和阿魏酸甲酯分别在氧化银催化下发生自由基仿生氧化偶联反应,合成得苯并二氢呋喃环结构化合物1,1经甲基化反应得2．1和2分别在无水碳酸钾、10％氢氧化钠水溶液等不同的碱性条件下进行反应,获得了11个苯并二氢呋喃环开环产物,即8—5′新木脂素类化合物3a～9b,实现了由苯并二氢呋喃新木脂素向8—5′新木脂素的转变,也为合成芪类化合物提供了一种新方法．C-8位上的吸电子基团如酯基的影响使苯并二氢呋喃环易在碱性条件下开环形成8-5′新木脂素类化合物．所合成化合物的结构由MS,IR,^1H NMR和^13C NMR进行了表征．     

8-5’新木脂素类化合物的合成方法研究

对羟基桂皮酸甲酯和阿魏酸甲酯分别在氧化银催化下发生自由基仿生氧化偶联反应, 合成得苯并二氢呋喃环结构化合物1, 1经甲基化反应得2. 1a和1和2分别在无水碳酸钾、10%氢氧化钠水溶液等不同的碱性条件下进行反应, 获得了11个苯并二氢呋喃环开环产物, 即8-5’新木脂素类化合物3a～9b, 实现了由苯并二氢呋喃新木脂素向8-5’新木脂素的转变, 也为合成芪类化合物提供了一种新方法. C-8位上的吸电子基团如酯基的影响使苯并二氢呋喃环易在碱性条件下开环形成8-5’新木脂素类化合物．所合成化合物的结构由MS, IR, 1H NMR和13C NMR进行了表征.     

木脂素类化合物的全合成研究

综述了本研究小组近几年在木脂素全合成研究中取得的新进展。主要包括三部分：通过β-酮酸酯偶联反应来合成去甲二氢愈创木酸及多种其它类型木脂素;通过氧化银偶联和DDQ合环首次合成黄酮木脂素(±)-Sinaiticin;通过Sharpless不对称双羟化为关键步骤首次手性合成1,4-苯并二氧六环类新木脂素。     

4-羟基异维A酸(4-N-茄尼基氨基苯酚)酯的合成

以异维A酸和茄尼醇为原料合成了4-羟基异维A酸(4-N-茄尼基氨基苯酚)酯,其结构经1H NMR,13C NMR,IR和MS表征.     

13-cis-维A酰衍生物合成方法的改进

改进并建立了以4-二甲氨基吡啶(DMAP)-对甲苯磺酸盐为催化剂,二环己基碳酰亚胺(DCC)为缩合剂直接用13-cis-维A酸与醇、酚或胺合成13-cis-维A酰衍生物的方法。合成了8种新目标化合物,收率80%～95%,核磁共振氢谱和碳谱研究表明,13-cis-维A酰部分的构型均保持不变。合成方法彻底抑制了反应中N-异维A酰基脲的副反应,而且反应条件温和,对于极易异构化的13c-is-维A酸的酯化和酰胺化反应十分有利。     

异维A酸糖基衍生物的合成及其细胞毒活性研究

采用两种方法合成了2类新的异维A酸糖基衍生物(5a~5d, 6a, 10a~10c, 11a), 并进行了结构表征与确认. 采用MTT法测试了它们对肺癌细胞(A549)等的细胞毒活性. 结果显示, 含有糖苷结构的异维A酸衍生物明显比含有糖酯结构的异维A酸衍生物具有更好的细胞毒活性; 将糖环上的乙酰基脱去后, 相应的化合物活性有明显提高.     

新型含双键的胆固醇单体及其液晶聚合物的合成

胆固醇分别与丁二酸酐、邻苯二甲酸酐反应制得带羧基功能基团的胆固醇单酯———丁二酸单胆固醇酯(3a),邻苯二甲酸单胆固醇酯(3b);3与甲基丙烯酸羟乙酯在DCC/DMAP催化下完成酯化反应合成了新型含双键的胆固醇单体(4a和4b);4经抽真空-冷冻-通氮气循环三次后真空封管聚合制得液晶聚合物(5a和5b),其结构经1H NMR,IR表征;5的热性能及液晶形态用DSC,TGA和POM研究。     

4-氧代-3（4H）-喹唑啉-5-羧酸的合成

以2-氨基-6-甲基苯甲酸为起始原料,通过合环反应生成两种4-氧代-3(4H)-喹唑啉-5-羧酸衍生物(1a, 1b), 1a, 1b分别经高锰酸钾氧化合成了4-氧代-3(4H)-喹唑啉-5-羧酸（2a, 2b）,其结构经¹H NMR, ¹³C NMR和MS表征。研究了投料比｛r［n(高锰酸钾) :n(5-甲基-3(4H)-喹唑啉-4-酮)］｝和反应温度等对收率的影响。结果表明：在最佳反应条件（r=7:1,中性高锰酸钾氧化,于90 ℃反应）下合成2总收率可达66%。     

(6R,7R)-7-氨基-3-[2-(4-甲基-5-噻唑)乙烯基]-8-氧代-5-硫-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸的合成

以1-磺丁基-3-甲基咪唑硫酸氢盐离子液体(b)为反应介质,7-氨基头孢烷酸(7-ACA,2)为原料,与4-甲基-5-甲酰基噻唑经缩合反应制得(6R,7R)-7-氨基-3-[2-(4-甲基-5-噻唑)乙烯基]-8-氧代-5-硫-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸(7-ATCA,1),其结构经1H NMR,13C NMR和IR表征。考察了离子液体及其用量,原料摩尔比r[n(4-甲基-5-甲酰基噻唑)∶n(2)],反应温度和反应时间对1收率的影响。在最佳反应条件[b为反应介质,b用量为20 m L,r=1.3,于65℃反应5 h]下,1收率可达90%以上。     

An efficient synthesis and reactions of novel indolylpyridazinone derivatives with expected biological activity

Reaction of 4-anthracen-9-yl-4-oxo-but-2-enoic acid (1) with indole gave the corresponding butanoic acid 2. Cyclocondensation of 2 with hydrazine hydrate, phenyl hydrazine, semicarbazide and thiosemicarbazide gave the pyridazinone derivatives 3a-d. Reaction of 3a with POCl(3) for 30 min gave the chloropyridazine derivative 4a, which was used to prepare the corresponding carbohydrate hydrazone derivatives 5a-d. Reaction of chloropyridazine 4a with some aliphatic or aromatic amines and anthranilic acid gave 6a-f and 7, respectively. When the reaction of the pyridazinone derivative 3a with POCl(3) was carried out for 3 hr an unexpected product 4b was obtained. The structure of 4b was confirmed by its reaction with hydrazine hydrate to give hydrazopyridazine derivative 9, which reacted in turn with acetyl acetone to afford 10. Reaction of 4b with methylamine gave 11, which reacted with methyl iodide to give the trimethylammonium iodide derivative 12. The pyridazinone 3a also reacted with benzene- or 4-toluenesulphonyl chloride to give 13a-b and with aliphatic or aromatic aldehydes to give 14a-g. All proposed structures were supported by IR, (1)H-NMR, (13)C-NMR, and MS spectroscopic data. Some of the new products showed antibacterial activity.     

1-脱氢松香酰基-3-取代硫脲以及5-(脱羧脱氢松香-4-基)-3-芳氨基- 1H-1,2,4-三唑化合物的合成与生物活性

以广西的优势资源松香为原料, 脱氢松香酸与亚硫酰氯、硫氰化钾分别在回流条件下反应6 h和1.5 h, 得到脱氢松香酰异硫氰酸酯, 产率52%; 然后与胺在加热回流条件下反应1.5 h, 得到11种1-脱氢松香酰基-3-取代硫脲4, 产率63%～94%; 4a～4f 分别与水合肼在搅拌下回流反应3～6 h, 得到6种5-(脱羧脱氢松香-4-基)-3-芳氨基-1H-1,2,4-三唑化合物5, 产率70%～94%; 所有化合物的结构均经IR, 1H NMR, 13C NMR和元素分析确认. 初步生物活性测试表明, 4e, 4f, 4j, 5b对枯草杆菌抑菌率较高, 特别是4j在浓度为50 mg/L时就达到较好效果; 4b, 4h, 4i, 5e在100 mg/L时对大肠杆菌的抑菌效果较好.     

3-Aza-cope rearrangement of quaternary N-allyl enammonium salts. Stereospecific 1,3 allyl migration from nitrogen to carbon on a tricyclic template

N-Allyl enamines can undergo a [3,3] sigmatropic rearrangement known as a 3-aza-Cope (or amino-Claisen) reaction. We explored a 3-aza-Cope reaction involving 1,3 allylic migration from nitrogen to carbon in N-allyl enammonium quaternary salts, exemplified by benzo[a]quinolizine 8 and pyrrolo[2,1-a]isoquinoline 13, with an interest in stereochemistry and mechanism. Salts 8 and 13 were accessed, respectively, through stereospecific allylation of hydroxy amines 4 and 11a/11b to give 7 and 12a/12b, which were dehydrated with trifluoroacetic acid. Allylic migration in these tricyclic tetrahydroisoquinolines occurred with high stereospecificity, with the major products 9 (from 8) and 15a (from 13) apparently deriving from a concerted suprafacial [3,3] rearrangement. The rearrangement of 8 to 9 was facile at 23 degrees C (t(1/2) = ca. 5 h) and was >98% stereospecific, whereas the rearrangement of 13 to 15a/15b required heating between 50 and 100 degrees C, with ca. 90-95% stereospecificity (t(1/2) = ca. 0.3 h at 100 degrees C). A deuterium-labeling experiment with 21 ((2)H-13) confirmed that allylic inversion accompanies the 1,3 migration en route to major isomer 22a ((2)H-15a), supporting the predominance of a concerted [3, 3] sigmatropic mechanism. However, the 5-10% loss of stereospecificity in the rearrangements of the pyrroloisoquinolines 13 and 21, reflected by formation of minor isomers 15b and 22b, respectively, indicates a minor nonconcerted reaction pathway.     

新型双卤代吡啶酰腙的合成及生物活性研究

以2-氯吡啶-4-甲酸甲酯(1)和水合肼缩合生成2-氯吡啶-4-甲酰肼(2),2与卤代(F,Cl,Br)对苯甲醛反应得到3种新型双卤代吡啶酰腙[C13H9N3OFCl(3a),C13H9N3OCl2(3b)和C13H9N3OClBr(3c)],其结构经1H NMR,13C NMR,IR和元素分析表征。紫外光谱证实,3a^3c与小牛胸腺DNA(ct-DNA)均产生了插入作用。荧光光谱显示,3a^3c均与牛血清蛋白BSA通过静态猝灭形成了复合物。3a^3c与ct-DNA,BSA的结合常数Kb及KA的关系均为3b>3c>3a。抑菌测试结果表明:3种酰腙化合物对大肠杆菌、金黄色葡萄球菌、枯草芽孢杆菌及铜绿假单胞菌等4种细菌的抑菌圈均超过8 mm。其中,3a对4种细菌的最大抑菌圈达10.97 mm。     

新型苯并咪唑杂多酸盐离子液体的制备及其在催化合成己二酸中的应用

以1-丁基苯并咪唑为起始原料,合成了1-丁基-3-(4-磺酸基丁基)苯并咪唑內盐(1),1-丁基-3-羧甲基苯并咪唑氯盐(2)和1,3-二丁基苯并咪唑溴盐(3);1~3分别与硅钨酸、磷钨酸和磷钼酸在水或者乙醇中反应,合成了5种新型的杂多酸盐离子液体——1-丁基-3-(4-磺酸基丁基)苯并咪唑硅钨酸盐(4a),1-丁基-3-(4-磺酸基丁基)苯并咪唑磷钨酸盐(4b),1-丁基-3-(4-磺酸基丁基)苯并咪唑磷钼酸盐(4c),1-丁基-3-羧甲基苯并咪唑硅钨酸盐(5)和1,3-二丁基苯并咪唑硅钨酸盐(6),其结构经1H NMR,13C NMR和IR表征。并考察了4~6在30%H_2O_2催化氧化环己烯制备己二酸反应中的催化效果。实验结果表明:4b的催化效果最好。在最佳反应条件[环己烯20 mmol,4b 0.16 mmol,n(环己烯)∶n(H2O2)∶n(ILs)=1∶4.4∶0.008]下,己二酸产率71%。     

Synthesis under microwave irradiation of [1,2,4]triazolo[3,4-b] [1,3,4]thiadiazoles and other diazoles bearing indole moieties and their antimicrobial evaluation

Microwave-assisted synthesis of some novel compounds, namely, 3-(2-methyl-1H-indol-3-yl)-6-aryl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 5a,b was accomplished via bromination of 2-methyl-3-[4-(arylideneamino)-5-mercapto-4H-[1,2,4]triazol-3-yl]-1H-indoles 3a,b. Also, new [1,3,4]thiadiazoles 12a,b, [1,2,4]triazoles 15a,b and [1,3,4]oxadiazoles 19a,b, with indole moieties, were prepared by cyclization of 1-[(2-methyl-1H-indole)-3-carbonyl]thiosemicarbazides 8a,b under microwave irradiation using different reaction conditions. Moreover, reaction of acid hydrazide 7 with ethyl 2-(N-phenylhydrazono)-3-oxobutanoate (20) gave the respective phenylhydrazonopyrazole derivative 21 under the reaction conditions employed. The structures of the synthesized compounds were assigned based on elemental analyses and spectral data (IR, (1)H-NMR, (13)C-NMR, MS). The antifungal and antibacterial activities of the new products were also evaluated.     

Facile and convenient synthesis of 2,6-disubstituted 4H-1,3-oxazin-4-one derivatives

Facile and convenient methods for the preparation of a variety of 2,6-disubstituted 4H-1,3-oxazin-4-ones 3 by three complementary methods are described. Treatment of the branched aliphatic imidate 2c,d with diketene 1 in the presence of a catalytic amount of acetic acid affords 2-substituted 6-methyl-1,3-oxazin-4-ones 3c,d , whereas the unbranched imidate 2b,e gave oxazines 3b,e and pyrimidines 4b,e (Method A). The reaction of acyl Meldrum's acid 5 with imidate 2 afford 2,6-disubstituted oxazine 3, though the alkylimidate with acetyl Meldrum's acid yielded 3 and 5-acetyl-1,3-oxazine-4,6-dione 8 (Method B). The cylodehydration of acylacetylcarboxamide 13 with acid, such as 70% perchloric acid or fluorosulfonic acid, afforded 1,3-oxazines 3 (Method C).     

Synthesis of 1,2-five-ring-annellated barrelenes via the intramolecular Diels-Alder reaction of acetylenic derivatives

The intramolecular Diels-Alder reaction conducted with acetylenic acylureas, obtained from carbodiimides, and the acetylenic acid 5 and its derivatives 13 gave the 1,2-annellated barrelene 14 (from 13a ) and the benzobarrelenes 8 (from 5 ) and 15 (from 13b ); in the case of 3-butynoic acid ( 1 ),[1,3]-H shift were observed. The formation of the azabarrelenes 16 (from 13c ) as an intermediate is postulated which looses HCN to afford the indolinone 17 . The acylureas 6 and 9 underwent isocyanate cleavage instead of [4+2] cyclization.