1-取代胺甲基-7,8-二去氢-4-羟基-3,7-二甲氧基-17-甲基-9α,13α,14α-吗啡烷-6-酮的合成

超声波辐射下, 以盐酸青藤碱为原料, 在其A环1-位碳上进行Mannich反应, 合成了2个新的取代胺甲基化合物 1a, 1b. 且由化合物1a与取代芳胺及吗啉通过胺交换反应合成了8个新的取代胺甲基化合物2a～2h. 所有新化合物的结构利用IR, MS, ¹H NMR及NOE差谱进行了表征.     

(E)-脱氢二聚白藜芦醇-11,11′,13,13′-四甲醚的全合成

以3,5-二甲氧基苯甲酸(1)为起始原料, 经过甲醇酯化、氢化铝锂还原、四溴化碳溴代和Wittig-Horner反应,高产率的合成了Wittig-Horner试剂(5). 化合物5与对羟基苯甲醛(6)的羟基保护产物(7)偶联得到化合物(8),后者经去甲氧基亚甲基保护和仿生氧化偶联反应成功地全合成了(E)-脱氢二聚白藜芦醇-11,11′,13,13′-四甲醚(10). 通过1H NMR、13C NMR、IR、HRMS等测试技术确定化合物10为二聚芪类化合物(E)-脱氢二聚白藜芦醇-11,11′,13,13′-四甲醚,总收率48.93%.     

伊马替尼衍生物的合成及细胞毒活性研究

以3-乙酰基嘧啶、2-甲基-5-硝基苯胺为起始原料,经加成、缩合、环化、还原得到中间体伊马替胺(6),再与异氰酸酯和芳酰基异硫氰酸酯胺解得到脲类(7a~7e)和芳酰基硫脲类(8a~8g)共12个化合物。目标化合物经过IR、1H NMR、13C NMR、HRMS等结构确证。采用四甲基偶氮唑盐(MTT)法考察目标化合物细胞毒活性,结果显示,目标化合物对所选肿瘤细胞的增殖活性具有一定抑制作用,其中化合物7d、7e、8d对人白血病细胞(K562)和人肝癌细胞(Hep G2)的抑制活性接近伊马替尼。     

青风藤有效化学成分与环氧合酶的对接研究

将青风藤中23个有效化学成分与COX-2酶对接,有四个化合物具有较低的结合自由能,其中以青藤碱为最低.进一步将这四个化合物与COX-1酶对接,发现这四个化合物与COX-1酶结合能力较弱,预示这四个化合物具有选择性抑制COX-2酶的能力.对青藤碱和COX-2以及COX-1酶的结合模式进行分析,发现青藤碱主要结合于COX-2酶的S′口袋,而COX-1酶的S′结合口袋中第523号残基由COX-2酶中的Val523变成了体积较大的Ile523,使得COX-1酶的S′结合口袋相对COX-2酶的结合口袋要小,从而导致青藤碱分子不能进入COX-1酶S′结合口袋.这成功解释了青藤碱选择性抑制COX-2酶的原因,与早期有关文献报道的实验结果相吻合,充分表明了对接模型的合理性,青藤碱等化合物可作为设计COX-2酶选择性抑制剂的先导化合物.     

水杨醛缩牛磺酸Schiff碱和还原Schiff碱的合成、晶体结构及其荧光性质

在甲醇溶液中,水杨醛和牛磺酸经缩合反应合成了水杨醛缩牛磺酸Schiff碱(1);1用硼氢化钠还原制得对应的其还原Schiff碱(2).1和2的结构经1H NMR,IR和元素分析表征.X-射线单晶衍射分析表明,2属单斜晶系,空间群P21/c,晶胞参数a=10.787 4(12)A,b=8.989 7(10)A,c=11....     

β-环糊精修饰碳糊电极测定盐酸青藤碱

研究盐酸青藤碱在β-环糊精(β-CD)修饰碳糊电极上的电化学行为,在此基础上建立了测定盐酸青藤碱的电化学新方法。盐酸青藤碱在β-CD修饰碳糊电极上是受吸附控制的电化学反应过程,在p H 6.6的柠檬酸–柠檬酸钠底液中,盐酸青藤碱在β-CD修饰碳糊电极上产生一对良好的氧化还原峰,峰电位分别为0.458 V和0.086 V。氧化峰电流与盐酸青藤碱的质量浓度在3.658 5~91.462 5 mg/L范围内呈良好线性关系,线性相关系数为0.995 4,检出限为1.229 3 mg/L。该方法应用于正清风痛宁片中盐酸青藤碱含量的测定,测定结果的相对标准偏差为5.82%(n=7),回收率在95.7%~107.4%之间。该方法简便、快速,结果准确,可用于盐酸青藤碱的测定。     

8-异戊烯基黄酮类天然产物的微波促进Claisen重排合成

8-异戊烯基黄酮是一类具有显著生物活性的天然产物.以2,4,6-三羟基苯乙酮和3,4-二羟基苯甲醛为原料,用氯甲基甲醚保护羟基,经羟醛缩合、碘催化环合、过氧丙酮(DMDO)氧化、O-异戊烯基化、微波促进的Claisen重排、脱甲氧甲基保护基、O-甲基化和异戊烯基侧链环合等反应步骤,完成了8-异戊烯基槲皮素-3-甲醚(1)、8-异戊烯基槲皮素-3,7,3',4'-四甲醚(2)和ArtochaminC(3)这3种8-异戊烯基黄酮类天然产物的合成.并对由微波促进的由5-O-异戊烯基黄酮类化合物合成8-C-异戊烯基黄酮类化合物的Claisen重排反应的关键步骤进行了探讨.所有合成的化合物经~1H NMR、~(13)C NMR和MS等结构确证.     

新型含杂环醚类手性配体的合成及其不对称催化性能

以L-酒石酸和二苯甲酮为原料,经酯化、缩酮、还原等反应合成了两个新型的含杂环醚类手性配体——(4S,5S)-5-甲基(2-甲氧基吡啶)-2,2-二苯基-1,3-二氧戊环-4-甲醇(7)和(4S,5S)-2,2-二苯基-1,3-二氧戊环-4,5-二甲基(2-甲氧基吡啶)(8),其结构经1H NMR,13C NMR和ESI-MS表征。以环己酮与对硝基苯甲醛的不对称aldol反应为探针反应,考察了7和8的不对称催化活性。实验结果表明,在最佳反应条件[8 0.015 mmol,在甲苯中于10℃反应96 h]下,8的催化效果较佳(ee值97.2%)。     

5-硝基-2H-四唑的合成、反应性及产物晶体结构的研究

5-氨基四唑(1)经过重氮化反应得到5-硝基四唑(5),5与甲醛反应得到2-羟甲基-5-硝基四唑(6),6与HCl或HBr反应分别得到5-5氯代四唑(7)和5-溴代四唑(8),采用MS,IR,1H NMR,13C NMR等技术对这些化合物进行了表征.用X射线单晶衍射法测定了化合物5-硝基四唑钠(4),5和6的晶体结构.化合物4属于三斜晶系,P-1空间群;化合物5和6均属于单斜晶系,P21空间群,化合物6的晶胞参数a=0.66131(18)nm,b=0.54905(15)nm,c=0.7566(2)nm,Z=2,V=0.27470(13)nm3,Dc=1.754g/cm3,F(000)=128,μ=0.160mm-1.     

4(3H)-喹唑啉酮类Schiff碱的合成与抗烟草花叶病毒活性

采用邻氨基苯甲酸经醋酐酰化闭环得2-甲基苯并噁嗪-4-酮, 水合肼回流合成2-甲基-3-氨基-4(3H)-喹唑啉酮, 在无水乙醇中与芳醛反应得4(3H)-喹唑啉酮类Schiff碱. 经元素分析, IR, 1H NMR, 13C NMR对所合成的化合物进行了结构确认和表征. 初步生物活性测试表明, 化合物3t具有较高的抗烟草花叶病毒活性.     

Synthetic protocols, molecular polarity, and 13C NMR correlations for 1-aryl- and 1-diarylmethylidene-1H-cyclopropa[b]naphthalenes

The Peterson olefination for alkylidenecycloproparene synthesis from a 1,1-disilylcycloproparene has been refined into five distinct protocols that have provided 43 new aryl- (5 and 6) and diaryl- (7 and 8), and aryl(phenyl)- (9 and 10) methylidene derivatives. The permanent dipole moments of these and other previously reported compounds have been measured and the direction of the dipole, to or from the cycloproparenyl moiety, established for each compound. The 13C NMR spectra are fully assigned and linear correlations of carbon chemical shift with the Hammett sigmap+ constants for each atom within the cycloproparene moiety are provided for the 8-11 compounds that comprise each substitution pattern present in 5-10.     

Reduction of inner sulfonium salts, thioethers, and sulfones derived from closo-[B12H12]2- by lithium in methylamine: a new route to mercaptododecaborates

Anions [Me2SB12H11]- (2) and [MeSB12H11]2- (3) can be reduced by excess lithium in methylamine at -15 degrees C to yield [HSB12H11]2- (1) after workup. Such behavior toward this reducing system is similar to that of alkyl aryl sulfides. The sulfone [MeSO2B12H11]2- (12) also yields 1 as a major boron product upon reduction, while alkyl aryl sulfones produce the corresponding arenes under the same conditions. Similarly, isomers of (Me2S)2B12H10 (4-6) are reduced by lithium in methylamine yielding dithiols [(HS)2B12H10]2- (7-9). The tetrabutylammonium salts of 1 and 7-9 are obtained in 80-90% yields and characterized by multinuclear NMR and mass spectrometry, the latter three compounds being isolated and characterized for the first time. The reduction reaction provides access to dithiols 7-9 for biological evaluation and use in synthesis. Thus, 2 and 4-6 can be easily converted to [R2SB12H11]- and (R2S)2B12H10 in a two-step reduction-alkylation procedure. 1,2-(Bn2S)2B12H10 (13) obtained by alkylation of the reduction product of 4 by benzyl chloride was characterized by single-crystal X-ray diffraction analysis. Crystal data for 1,2-(Bn2S)2B12H10.CD3CN: C2/c (No. 15), a = 13.666(1) A, b = 16.978(1) A, c = 14.667(1) A, beta = 91.08(1) degrees, Z = 4.     

Complete assignments of 1H and 13C NMR spectral data for three sesquiterpenoids from Inula helenium

The complete assignments of all the (1)H and (13)C NMR signals of three sesquiterpene lactones, 4-oxo-5(6),11-eudesmadiene-8,12-olide (1), 4-oxo-11-eudesmaene-8,12-olide (2) and (1(10)E)-5beta-Hydroxygermacra-1(10),4(15),11-trien-8, 12-olide (3), were carried out by various 2D NMR experiments. Compounds 1-3 were isolated from the roots of Inula helenium for the first time. Among them, 1 was identified as a new nor-sesquiterpene lactone, and 2 was isolated from a natural source for the first time. The (13)C-NMR data of compound 3 was also reported for the first time.     

P(CH(3)NCH(2)CH(2))(3)N as a dehydrobromination reagent: synthesis of vitamin A derivatives revisited.

Although P(CH(3)NCH(2)CH(2))(3)N (1) was found to be less effective than 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in the removal of hydrogen bromide from vitamin A intermediates 13-cis-10-bromo-9,10-dihydroretinyl acetates (6) and 14-bromo-9,14-dihydroretinyl acetate (11) when the reaction was carried out in refluxing benzene, in acetonitrile at room temperature it was superior to DBN and DBU. A (31)P NMR study of this reaction suggests that the carbanion generated from acetonitrile-d(3) in the presence of 1 is the basic species that initiates the elimination step. Diastereoselectivity of the nucleophilic addition of (Z)-HC triple bond C(CH(3))=CHCH(2)OH to the carbonyl group of (E)-2-methyl-4-(2',6',6'-trimethyl-1'-cyclohexen-1'-yl)-3-butenal (2) was only moderate (20%), and (9R,10S)-13-cis-11,12-didehydro-9,10-dihydro-10-hydroxyretinol (3b) predominated. The LiAlH(4) reduction of the C triple bond C bond in the diastereoisomeric diols 3 afforded 13-cis-9,10-dihydro-10-hydroxyretinols 4a and 4b as major products together with 11-cis-13-cis-isomers and the deoxygenated compound (3EZ,5EZ,8E)-3,7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3,5,8-nonatetraene (9). Reaction of 15-acetates of the pure diastereoisomeric allylic alcohols 4a and 4b with PBr(3) occurred with significant but not identical retention of configuration, and with concomitant formation of the rearranged bromide 11.     

(E)-脱氢二聚白藜芦醇四甲醚的全合成

以3, 5-二甲氧基苯甲酸(1)和对羟基苯甲醛(6)为起始原料, 经过以仿生氧化偶联为关键步骤的八步反应,对化合物10进行了全合成。通过1H NMR, 13C NMR, IR, HRMS等方法确定化合物10的结构为7, 8 - trans-7', 8'-trans-二聚芪类化合物,即(E)-脱氢二聚白藜芦醇四甲醚,结果表明利用本文方法成功合成了目标化合物。     

Photolysis and Cycloaddition Reactivity of Diferrocenyl Substituted Cyclopentadienone

The photolysis results of new diferrocenyl substituted cyclopentadienone(3) show that sunlight and air play an important role in the decomposition of compound 3, and two new compounds, 2-cyclopentenone(4) and α-pyrone(5), were obtained via photolysis of compound 3. The photolysis process was investigated by ¹H NMR, and a plausible mechanism for the formation of compound 5 was deduced. The cycloaddition reactions of substituted cyclopentadienones(3, 7, 9) with maleimide gave substituted imides 8, 10, 11, 12 and an unprecedented diferrocenyl substituted 1H-pyrrol-3(2H)-one derivative 13, respectively. The structures of compounds 4, 5, 8, 10, 11, 12 and 13 were confirmed by X-ray single crystal diffraction analysis technique.     

Eine neue Synthese von 8-Hydroxy-2-methyl-1,2,3,4-tetrahydroisochinolin

A new Synthesis of 8-Hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline Vilsmeier formylation of N-[2-(3,5-dimethoxyphenyl)ethyl]-trifluoroacetamide ( 5 ) yielded the aldehyde 6 , which under mild basic conditions was hydrolyzed to 7 and cyclized to 6,8-dimethoxy-3,4-dihydroisoquinoline ( 3 ). Methylation of 3 and reduction of the double bond in 10 afforded 6,8-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline ( 11 ). The methoxyl group at C(6) was selectively demethylated and the free hydroxyl group in 12 was phosphorylated to give 13 . Reduction of the latter with potassium in liquid ammonia yielded 8-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline ( 2 ), which was demethylated to the title compound 1 .     

A cytotoxic and apoptosis-inducing sesquiterpenoid isolated from the aerial parts of Artemisia princeps PAMPANINI (Sajabalssuk)

Repeated silica gel and octadecyl silica gel (ODS) column chromatography of the aerial parts of Artemisia princeps PAMPANINI (Sajabalssuk) led to the isolation of a new sesquiterpenoid, 3-((S)-2-methylbutyryloxy)-costu-1(10),4(5)-dien-12,6 alpha-olide (2), along with two previously reported sesquiterpenoids: 8 alpha-angeloyloxy-3beta,4 beta-epoxy-6 beta H,7 alpha H,8 beta H-guaia-1(10),11(13)-dien-12,6 alpha-olide (1, carlaolide B) and 3beta,4 beta-epoxy-8 alpha-isobutyryloxy-6 beta H,7 alpha H,8 beta H-guaia-1(10),11(13)-dien-12,6 alpha-olide (3, carlaolide A). The structure of compound 2 was elucidated by spectroscopic data analysis, including one dimensional (1D) and two dimensional (2D) nuclear magnetic resonance (NMR) experiments. Of the isolates, compound 2 exhibited potent cytotoxicity against human cervix adenocarcinoma cells and induced apoptosis.     

四氟乙烯齐聚体的反应 四氟乙烯四、五聚体和芳香胺的反应

前已报道四氟乙烯四聚体(全氟-3,4-甲基己烯-3)(1)、五聚体(全氟-3,4-二甲基-4-乙基己烯-2)(2)和脂肪烷氧以及脂肪胺的亲核反应.本文报道化合物1,2和芳香胺如苯胺、β-萘胺的反应.由于烯烃1、2双键处于分子中间,因而当亲核试剂进攻时,双键容易发生重排,生成的末端基烯烃更具反应性,故导致一取代、二取代、三取代以及环化降解等复杂产物.