白屈菜红碱的全合成

以2,3-二甲氧基-6-溴苄醇(1)为起始原料,经过6步反应合成关键中间体2,3-二甲氧基-6-碘苯甲酸甲酯(7),通过金属钯催化下与中间体(8)的串联反应策略一步构筑了白屈菜红碱的B/C环,并以10步60.9%的总收率完成了白屈菜红碱的全合成,同时对关键的金属钯催化串联反应机理进行了初步探讨,为高效合成苯并[c]菲啶类生物碱提供了一条简便路线.     

一种去掉白屈菜中白屈菜碱的分离方法

白屈菜草药分别用甲醇和丙酮做提取液,于索氏提取器中提取。提取物经GC/MS分析,结果显示,甲醇提取物中鉴定出的生物碱有原阿片碱、人血草碱、二氢血根碱、白屈菜赤碱和血根碱,没有白屈菜碱。丙酮提取物中鉴定出的生物碱只检测到了白屈菜碱,没有检测到其它生物碱。本文为提取或去掉白屈菜中白屈菜碱,提供了一种分离方法。     

小果博落回对照物质及其核磁共振氢谱指纹图的创建

采用规范化的程序获取6个不同来源小果博落回样品的对照物质(CSPD)及其^1H NMR图谱;从小果博落回CSPD中分得6个单体成分,其结构分别被鉴定为二氢血根碱(1)、二氢白屈菜红碱(2)、6-甲氧基二氢血根碱(3)、6-甲氧基二氢白屈菜红碱(4)、齐墩果酸(5)和原阿片碱(6)。通过各单体化合物的^1H NMR图谱与CSPD的^1H NMR图谱的对比研究,实现了小果博落回的^1H NMR指纹图的解析。研究结果表明：6个不同来源的小果博落回样品,其^1H NMR指纹图有很好的重现性和高度的特征性,并主要显示以上生物碱类成分的特征共振信号,可做为其基源鉴定的参考。     

延胡索素乙有关化合物的合成 Ⅰ.四氢非洲防己碱去甲基化合物的酯化和烷基化及小蘖碱去亚甲基化合物的烷基化和氢化

用三氯化铝、氢溴酸和氢碘酸三种方法将四氢非洲防己碱上的四个甲基去除,得到2,3,9,10-四羟基-5,6,13,13a-四氢-8-二苯骈[a,g]喹诺里嗪氢卤酸盐.后者在吡啶存在下与丙酰氯、丁酰氯、苯甲酰氯、对硝基苯甲酰氯、肉桂酰氯和3,4,5-三甲氧基苯甲酰氯作用,得到相应的酯;与重氮丁烷作用得到2,3,9,10-四丁氧基-5,6,13,13a-四氢-8-二苯骈[a,g]喹诺里嗪氢溴酸盐.小蘖碱盐酸盐与三氯化铝作用时只有亚甲基断裂,然后与硫酸二乙酯作用,得到2,3-二乙氧基-9,10-二甲氧基-8-二苯骈[a,g]喹诺里嗪重硫酸盐.此物用接触氢化法还原时得二氢化合物,用锌和硫酸还原时得四氢化合物.     

环境污染物质活性与电子结构——芳烃致癌湾区历程的CNDO/2计算研究

为了探讨“湾区原程”,本文采用CNDO/2分子轨道方法计算了苯并[c]菲,1.2—二氢苯并[c]菲等。计算结果表明,代谢物的湾区碳原子净电荷与其致癌活性有关。代谢物的致癌活性随着湾区碳原子的正电荷增加而变大。     

氯化两面针碱合成方法的改进

以6-溴-3,4-二甲氧基苯甲醛和6,7-亚甲二氧基-1-萘胺为起始原料,经还原胺化、分子内Heck偶联、氧化芳构化、甲基化以及离子交换等五步反应,完成了氯化两面针碱的合成,并对关键步骤分子内Heck偶联反应条件进行了探索,结果表明该偶联反应在醋酸钯、三(邻甲苯基)膦和N,N'-二甲基甲酰胺体系中反应效果最佳,收率显著提高.该优化条件为结构类似苯并[c]菲啶类生物碱母核结构的构建提供了借鉴.     

5-取代氨基-12-取代苯并[c]菲啶衍生物的合成、晶体结构及生物活性

为了寻找新的高活性农药, 利用2-甲基苯甲腈与不同的醛反应, 再通过2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ)脱氢或NaH和CH3I氮甲基化, 合成了3个系列共18个5-取代氨基-12-取代苯并[c]菲啶衍生物, 其中15个是未见文献报道的化合物. 它们的结构均经1H NMR, 13C NMR, IR和高分辨质谱表征; 用X射线衍射测定了化合物5-氨基-12-(4-二乙氨基苯基)-11,12-2H-苯并[c]菲啶盐酸盐(3c)的晶体结构. 初步的生物活性测试结果表明, 部分化合物具有一定的杀菌活性和促进黄瓜子叶生根活性.     

两面针抗肿瘤有效成分的研究

自两面针根中共分离出七种生物碱,其中六种生物碱经鉴定分别为氯化两面针碱(1)、氧化两面针碱(2)、二氢两面针碱(3)、6-甲氧基-5,6-二氢白屈菜红碱(4)、α-别隐品碱(5)和茵芋碱(6),7的结构尚待进一步研究。动物试验结果表明,1和4能延长小鼠艾氏腹水癌的生命;2、3、5和6则无明显活性。1已在临床试用,初步观察,对慢性粒细胞型白血病有近期疗效。     

毛细管电泳-电化学发光同时测定博落回果实中血根碱和白屈菜红碱的含量

建立了同时检测博落回果实中血根碱和白屈菜红碱含量的毛细管电泳电致化学发光新方法.该方法应用于博落回果实中血根碱和白屈菜红碱的测定,加标回收率为91%~100.3%.     

钯催化[2+2+2]环化反应制备5,6-二氢苯并菲啶衍生物

菲啶骨架化合物是一类重要的有机分子并广泛存在于天然产物中,也是一类重要的抗菌抗癌的生物活性分子.通过钯催化二炔和芳卤经[2+2+2]环化加成反应,发展了一种高效实用的制备二氢菲啶衍生物的Domino方法.所合成目标产物的结构经IR、1H NMR、13C NMR和HRMS表征确证,其中7,12-二苯基-5-对甲苯磺酰基-5,6-二氢苯并[j]菲啶-10-乙酮(3b)的结构还通过X射线单晶衍射分析确认.     

Capillary electrophoretic determination of sanguinarine and chelerythrine in plant extracts and pharmaceutical preparations

Capillary electrophoresis was employed to determine the principal quaternary benzo[c]phenanthridine alkaloids, sanguinarine and chelerythrine, in two plant extracts and one oral hygiene product. Phosphate-Tris buffer of pH 2.5 was used as a background electrolyte, limits of detection were 3 micromol/l(-1) (sanguinarine) and 2.4 micromol,l(-1) (chelerythrine) using UV detection at 270 nm. The method, which correlated well with HPLC, is suitable for serial determination of sanguinarine and chelerythrine in plant products and pharmaceuticals.     

Analysis of alkaloids in Macleaya cordata (Willd.) R. Br. using high-performance liquid chromatography with diode array detection and electrospray ionization mass spectrometry

A method for the analysis of alkaloids in Macleaya cordata (Willd.) R. Br. using high-performance liquid chromatography with diode array detection and electrospray ionization mass spectrometry (HPLC-DAD-ESI/MS) was developed. Using protopine (PRO), allocryptopine (ALL), sanguinarine (SA), and chelerythrine (CHE) as the model components, different columns for the separation and different mobile phases for the signal intensities of alkaloids in ESI/MS were investigated, respectively. The results showed that good separation and high signal intensities can be obtained on a high carbon loading (17%) reversed-phase C(18) column with 30 mM formic acid in mobile phase for the analysis of alkaloids. Under the optimal separation condition and UV detection (284 nm), linearity of the six alkaloids was obtained over concentration range from 0.05 to 100.00 microg/ml. The limit of detection (LOD) was 1.62, 1.87, 1.79, 1.76, 1.10, and 0.94 ng/ml for SA, CHE, PRO, ALL, dihydrosanguinarine (DHSA), and dihydrochelerythrine (DHCHE), respectively. The LODs with ESI/MS detection were lower three orders of magnitude than those obtained with UV detection. The proposed method could be used to control quality of the raw materials of the herb more comprehensively.     

Palladium-catalyzed tandem reaction to construct benzo[c]phenanthridine: application to the total synthesis of benzo[c]phenanthridine alkaloids

A concise and efficient synthesis of benzo[c]phenanthridines was accomplished by the palladium-catalyzed ring-opening coupling of azabicyclic alkene with o-iodobenzoates, followed by tandem cyclization. The strategy was successfully applied in the total synthesis of benzo[c]phenanthridine alkaloids such as sanguinarine, chelerythrine, nitidine and avicine.     

Seasonal variation in alkaloid composition and antiproliferative activity of <Emphasis Type="Italic">Stylophorum lasiocarpum</Emphasis> (Oliv.) Fedde

Stylophorum lasiocarpum (Oliv.) Fedde (Papaveraceae) belongs to traditional Chinese medicine herbs but there was minimal information on the content of alkaloids in this plant. Extracts from the aerial part and roots were examined by liquid chromatography with UV and mass spectrometric detection, with nineteen alkaloids identified. Changes in alkaloid content over the entire vegetation period of a one- and two-year old plant were studied. The protoberberine alkaloids, coptisine and stylopine, were found to be the main substances in extracts of the aerial part irrespective of the plant’s age and time of harvest. Variable amounts of protopine, sanguinarine, chelerythrine, chelirubine, macarpine, chelilutine and berberine were also recorded in the aerial part. The roots contained significantly larger quantities of all alkaloids than the aerial part with the levels of most alkaloids varying from May to October, peaking in the middle of the vegetation period. Coptisine was the dominant alkaloid in all samples. The antiproliferative activities of the root extract and of seven individual alkaloids were tested on A375 human malignant melanoma cells. The significant dose-dependent toxicity of the root extract was attributed largely to the quaternary benzo[c]phenanthridine alkaloids, macarpine and sanguinarine.     

Effects of the limited analyte solubility on its mobility and zone shape: electrophoretic behavior of sanguinarine and chelerythrine around pH 7

Electrophoretic mobilities and shapes of zones of sanguinarine and chelerythrine in aqueous media around pH 7 are affected by limited solubility of their uncharged forms and by the pH-dependent chemical equilibrium between cationic and uncharged forms of these alkaloids. The sanguinarine solubility in sodium MOPS of pH 7.4 was estimated at 50 micromol x L(-1). Sanguinarine zones in this buffer have the shape of tailed peak with concentration-independent mobility if the injected sanguinarine concentration exceeds this solubility limit only slightly. The chelerythrine solubility is higher because of lower dissociation constants of its cations. Precipitation of sanguinarine and chelerythrine with the phosphate anions decelerates their electrophoretic transport in phosphate buffer. Sanguinarine solubility is 5 micromol x L(-1) at the most in 13 mmol x L(-1) sodium phosphate buffer of pH 7.4. Acidifying of the sample up to pH 3 decreases the tailing of the peaks of sanguinarine and chelerythrine and contributes to the rise of sharp maxima of their migrating zones. Any capillary coating deteriorates the peak shape.     

Capillary zone electrophoretic studies of interactions of some quaternary isoquinoline alkaloids with DNA constituents and DNA

Capillary zone electrophoresis was applied for the investigation of interactions of some quaternary isoquinoline alkaloids, namely sanguinarine, chelerythrine, berberine, and jatrorrhizine, with DNA constituents and with DNA. None of these alkaloids attach covalently to nucleotides or to the whole DNA under physiological conditions. The interaction with DNA constituents is a noncovalent complexation based on weak intermolecular forces. Electrostatic attraction participates in the interaction but other types of intermolecular forces are involved as well. Cations were identified as the most probable interacting forms of the alkaloids. The interaction with compounds derived from purine was always stronger than those derived from pyrimidine. All alkaloids behaved analogously and similarly to ethidium bromide, the classic DNA intercalator. Stability constants K (in l.mol(-1)) for sanguinarine and chelerythrine in phosphate buffer of pH 7.4 (I(S) = 30 mM) ranged from tens to hundreds.     

Site-specific binding of chelerythrine and sanguinarine to single pyrimidine bulges in hairpin DNA

Spectrofluorometric titration, electrospray ionization time-of-flight mass spectrometric and UV melting methods were employed to study the binding of chelerythrine and sanguinarine to bulged DNA. The results showed that both alkaloids bind specifically to single pyrimidine (C, T) bulge sites. The ability of sanguinarine to bind to both regular and bulged hairpins was found to be stronger than that of chelerythrine, but the binding selectivity of chelerythrine toward single-base bulges was much larger than that of sanguinarine. Figure Association constants for chelerythrine and sanguinarine toward regular and single-base bulged hairpins obtained from fluorometric analysis     

Alkaloids induce programmed cell death in bloodstream forms of trypanosomes (Trypanosoma b. brucei)

The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine) induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC(50) below 10 microM) was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation.     

Alkaloids from Papaver coreanum

The alkaloid pattern of the endemic plant Papaver coreanum Nakai (Papaveraceae) was determined for the first time. Eight alkaloids could be identified by LC/ESI-MS/MS and high-resolution mass spectrometry. Among them, protopine and allocryptopine represent the main components. Besides norsanguinarine, sanguinarine, dihydrosanguinarine, oxysanguinarine, lincangenine, and cryptopine, some other trace alkaloids were found whose structures remain unknown.     

Inhibitory activity of dihydrosanguinarine and dihydrochelerythrine against phytopathogenic fungi

The antifungal activities of dihydrosanguinarine and dihydrochelerythrine, isolated from the leaves of Macleaya microcarpa, were evaluated on 12 plant pathogenic fungi; the two compounds exhibited the highest antifungal activity against Botrytis cinerea Pers. Among the 11 tested plant pathogenic fungi in vitro, the two compounds showed the highest antifungal activity against B. cinerea Pers, with 95.16% and 98.32% mycelial growth inhibition at 50 μg mL?1, respectively. In addition, the two compounds inhibited spore germination in vitro in a concentration-dependent manner. They also showed potent protective and curative effects against Erysiphe graminis and B. cinerea in vivo. This is the first report on the antifungal activity of dihydrosanguinarine and dihydrochelerythrine against pathogenic plant fungi.