可变误差多面体法用于多种维生素的同时测定

本文基于对多元校正分析模型的简要讨论,探索了应用可变误差多面体法同时测定维生索B₁,B₂,B₆和烟酰胺的可行性。其结果准确度和精密度均较满意。维生素B₁,B₂,B₆及烟酰胺的回收率分别是99.8±0.9%(CV),100.1±0.8%(CV),100.2±2.1%,100.1±0.7%(CV)。结果表明,通过公式K_S=A_SC_S^T(C_SC_S^T)^-1计算校正系数矩阵K_S,并结合可变误差多面体法这一直接求解方法,能有效地提高分析结果的准确度,克服组分间的交互作用及病态,是多元校正分析的较佳策略之一。     

联苯双酯对大鼠黄曲霉毒素B1代谢及肝毒性的影响

目的研究抗肝炎药联苯双酯对大鼠黄曲霉毒素B₁代谢和肝毒性的影响。方法大鼠po联苯双酯300 mg·kg^-1·d^-1, 连服3 d后ip黄曲霉毒素B₁1.5 mg·kg^-1。给黄曲霉毒素B₁16 h后测定血清ALT和AST水平,观察联苯双酯对黄曲霉毒素B₁引起肝损伤的保护作用以及对体外代谢的影响。结果联苯双酯(300 mg·kg^-1·d^-1,连服3 d)可明显降低黄曲霉毒素B₁引起的大鼠血清转氨酶升高，增加低毒代谢产物AFM₁的生成。联苯双酯还可增加大鼠肝脏细胞色素P450总量和胞浆GSH含量，诱导P450 2B1介导的PROD和GST的活性。此外，联苯双酯对P450 3A介导的红霉素脱甲基酶和P450 1A介导的EROD也有一定的诱导作用。结论联苯双酯可通过增加大鼠肝脏对AFB₁代谢的解毒功能起到肝保护作用。     

1-(1-取代苯基)-2-(1H-1,2,4-三唑或苯并三唑基)-O-(取代苄基)乙酮肟醚类化合物的合成及抗真菌活性

报道了29个新的1-(1-取代苯基)-2-(1H-1,2,4-三唑或苯并三唑基)-O-(取代苄基)乙酮肟醚类化合物的合成与体外抗菌试验。结果表明,大多数化合物对大部分真菌有抑菌活性,化合物T₁,T₄,T₆,T₁₁,T₁₂,B₁,B₃,B₄和B₆对部分真菌抑菌活性优于或相当于奥昔康唑。     

仙鹤草根芽中新异香豆精甙的结构研究

从仙鹤草根芽的苯提取物和丙酮提取物中分得反式对羟基肉桂酸酯的同系物混合物(Ⅵ)和一个新的异香豆精甙(Ⅶ)。通过理化性质,波谱分析(UV,IR,¹HNMR,MS,CI-MS-MS)及化学降解,Ⅵ被确定为反式对羟基肉桂酸C₂₂,C_24～32,C₃₄直链一元饱和醇的酯,Ⅶ被确定为仙鹤草内酯-6-O-β-D-葡萄吡喃糖甙。其中Ⅶ和反式对羟基肉桂酸C_20～32,C₃₄直链一元饱和醇酯为新化合物。     

苯丙烯酸类衍生物和类似物的合成及其抗炎和抗癌活性研究(英文)

近年研究表明,炎症和癌症都与花生四烯酸的代谢产物环氧酶和5-脂氧酶密切相关。据此选择对环氧酶或5-脂氧酶具有抑制作用的苯丙烯酸类化合物作为抗炎、抗癌先导化合物,并对其酯类衍生物及其苯乙烯酮类类似物进行初步探讨。本文作者设计并合成上述类型化合物共十九个,其中十五个为未见文献报道的新化合物,并经红外光谱、¹H-核磁共振光谱及元素分析等证实其化学结构。对所合成的化合物进行了抗炎及抗癌药理活性初步筛选。体内抗炎实验表明,所合成的苯丙烯酸类化合物Ⅰ_A,Ⅰ_B,Ⅰ_C人及其酯类衍生物Ⅱ_2A,Ⅱ_2C,Ⅱ_5C和苯乙烯酮类似物Ⅲ_C对巴豆油诱发的小鼠耳廓肿胀均有不同程度和抑制作用。体外抗癌作用初步筛选结果表明,化合物Ⅰ_B,Ⅱ_5A,Ⅱ_5C,及Ⅲ_D对HL-60人癌细胞均有较好的抑制作用。值得注意的是,化合物Ⅰ_B和Ⅱ_5C不仅对体外HL-60人癌细胞具有明显的抑制作用,而且对巴豆油所致小鼠炎症亦有较强的活性。深入的药理实验还在进行中。     

3-苯基-4(1H)喹啉酮羟基衍生物的合成及其抗骨质疏松活性

目的设计并合成7-羟基-3-(取代)苯基-4(1H)喹啉酮化合物及其相应的5-羟基-3-(取代)苯基-4(1H)喹啉酮化合物并考察其抗骨质疏松活性。方法以间氨基酚为原料,选择改良的Gould-Jacobs反应路线同时合成7-羟基-3-(取代)苯基-4(1H)喹啉酮4个(A_1～4)及其相应的5-羟基-3-(取代)苯基-4(1H)喹啉酮4个(B_1～4),通过骨细胞筛选实验以及羟磷灰石吸附实验分别考察其促骨形成作用和趋骨性。结果共合成了新化合物8个(A_1～4,B_1～4),其结构经IR,MS,1HNMR和元素分析确证。骨细胞筛选实验结果表明,B₃有促骨形成作用,但作用弱于芒柄花黄素;羟磷灰石吸附实验结果表明,羟磷灰石对B₁,B₂和B₄有一定的吸附,其中对B₁和B₂的吸附作用强于四环素。结论 5-羟基-3-(取代)苯基-4(1H)喹啉酮化合物有促骨形成作用并具有一定的趋骨活性。     

应用薄层扫描研究大鼠一次口服硝硫苯酯的药代动力学

本文建立了血浆中硝硫苯酯TLC扫描定量法,并可同时测定血浆中代谢物硝硫氰胺浓度。该法专一、灵敏。大鼠单剂ig硝硫苯酯200mg/kg后,血浆硝硫苯酯C_max为0.510μg.ml^-1,t_max为6 h,药—时曲线符合二室模型。t1/2ka,t1/2a、t1/2β分别为1.503,2.829和17.769 h;k₁₀,k₂₁和k₁₂分别为0.068,0.141和0.075h^-1,∫₀^∞cdt为12.367μg·h·ml^-1。本文还证明硝硫苯酯在吸收后,有部分转变为硝硫氰胺,其C_max为0.283μg·ml^-1,t_max为6 h。硝硫苯酯和硝硫氰胺曲线下∫₀³⁶cdt分别为9.211和4.644μg·h·ml^-1,后者约为前者的50%。     

X-射线单晶衍射法研究双炔失碳醇α-差向异构体的构型

本文报道有抗生育作用和雌激素活性的双炔失碳醇α-差向异构体的构型研究。采用重结晶法、低压硅胶柱色谱与HPLC相结合的方法,制得单晶纯品。经HPLC,IR,MS,¹HNMR证实。经Ⅹ-射线单晶衍射法测定,晶体属正交晶系,空问群为P222₁,晶胞参数为a=6.777(2),b=12.125(4),c=25.292(8),V=2078.5(1.2)。晶体结构采用直接法和Fourier技术得到,经最小二乘法修正,最后的偏离因子R=0.039。结构表明:其相对构型中,C₂,C¹⁷之乙炔基为α-型,结合合成原料构型推定C₂为R型,C₁₇为R型。     

伊维菌素(Ivermectin)晶体结构的研究

用单晶X射线衍射法测定了伊维菌素Ivermectin(H₂B_1a)的结构。Ivermectin由大于80%的H₂B_1a和小于20%的H₂B_1b组成。H₂B_1a属单斜晶系,C2空间群,晶胞参数为a=40.763(6)A,b=9295(3)A,c=14.966(3)A,β=106.93(1)°,V=5425(2)A³,Z=4,Dc=1.156g·cm^{-3,μ(MoK_∞)=0.084mm-1,R=0.0658。H₂B_1a呈沿C轴排列的链状结构,同时通过2次轴对称,实际结构为由两条链状分子呈平行分布,相互间距离一定,但方向相反的双链,类似于生物大分子的链状结构。}     

国家食品药品监督管理局国家药品标准修订件-马来酸桂哌齐特

本品为(E)-1-[4-(3'',4'',5''-三甲氧基肉桂酰基)-1-哌嗪]乙酰吡咯啶顺丁烯二酸盐。按干燥品计算,含C₂₂H₃₁N₃O₅·C₄H₄O₄应为98.0%~102.0%。     

Synthesis and antiviral properties of (Z)-5-(2-bromovinyl)-2'-deoxyuridine

(Z)-5-(2-Bromovinyl)uracil was obtained by photoisomerization of the E. isomer. Similarly, (E)-5-(2-bromovinyl)-2'-deoxyuridine gave the required Z isomer. (Z)-5-(2-Bromovinyl)-2'-deoxyuridine is much less active against herpes simplex virus type 1 (HSV-1) and somewhat less active against herpes simplex virus type 2 than is the E isomer. Both isomers show similar activity against vaccinia virus. Therefore, the highly potent and selective activity of (E)-5-(2-bromovinyl)-2'-deoxyuridine against HSV-1 is due to its E configuration.     

Cerebrosides from longan arillus

From the pulp of Euphoria longana (Longan Arillus), three cerebroside molecular species have been isolated. Six known cerebrosides, soyacerebrosides I and II, 1-O-beta-D-glucopyranosyl-(2S,3R,4E,8E)-2-(2'-lignoceroylamino)-4,8-octadecadiene-1,3-diol (longan cerebroside I) and its 8Z isomer (longan cerebroside II), momor-cerebroside I, and phytolacca cerebroside, were identified as major components of these cerebroside molecular species. All the cerebrosides were shown to be a mixture of geometrical isomers (8E and 8Z) of sphingosine-type or phytosphingosine-type glucocerebrosides possessing 2-hydroxy fatty acids. The structures of these cerebrosides have been determined on the basis of chemical and spectroscopic evidence.     

Studies on tomaymycin. II. Total syntheses of the antitumor antibiotics, E-and Z-tomaymycins

The total syntheses of naturally occurring E-tomaymycin (1E) and its olefinic geometrical isomer, Z-tomaymycin (1Z) are described. The Z-isomer was found to have the same anti-bacterial activity as E-isomer (1E).     

异三尖杉酯碱的合成及其异构体的分离

本文报道对实验动物肿瘤有抑制作用的异三尖杉酯碱的合成。以天然的三尖杉碱为原料,经过三尖杉碱-5-甲基-2-氧己酸酯与α-苄氧溴乙酸酯和活化锌进行Reformatsky反应,产品为苄氧异三尖杉酯碱及其三个立体异构体的混合物(8),收率51%。所含四个异构体的量相近。经旋转薄层层析分离为(8 a)和(8 b)两部分。分别以10%钯炭氢解生成(9 a)和(9 b),氢解产物再分别分离为(9 a₁),(9 a₂)和(9 b₁),(9 b₂)。(9 b₁)的物理常数和各种光谱均与天然异三尖杉酯碱一致。根据核磁共振光谱推测了其它三个立体异构体的绝对构型。     

Conformational analogues of dopamine. Synthesis and pharmacological activity of (E)- and (Z)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides.

(E)- and (Z)-(+/-)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides were synthesized as part of a program to assess the importance of conformational isomerism with respect to the various peripheral biological actions of dopamine. Although neither of the compounds possessed dopaminergic activity in the canine renal blood-flow model, both agents were weak alpha-adrenergic agonists and exhibited cardiostimulatory properties similar to dopamine. The E isomer was apprxoximately 5 times more potent than the Z isomer in its alpha-adrenergic activity and approximately 15 times as potent in its cardiac effects. Possible reasons for the lack of renal dopaminergic activity exhibited by the E isomer are presented.     

2,3-Epoxy-10-aza-10,11-dihydrosqualene, a high-energy intermediate analogue inhibitor of 2,3-oxidosqualene cyclase.

2,3-Epoxy-10-aza-10,11-dihydrosqualene, a high-energy intermediate analogue inhibitor of 2,3-oxidosqualene (SO) cyclase was obtained by total synthesis. This involved the preparation of three main building blocks: (1) C17 squalenoid N-methylamine, (2) 3-(diphenylphosphinoyl)propanal, and (3) 5,6-epoxy-6-methylheptan-2-one. The final stages of the reconstruction of the 6E double bond were obtained by a Wittig-Horner reaction which was modified for poorly reactive systems. This compound was designed to mimic the C-8 carbonium ion formed during SO cyclization. Its inhibitory activity on various SO cyclases was evaluated and compared with the 6 Z isomer which has an unfavorable geometry. Only isomer 6 E, the carbocation analogue, was active on SO cyclases from rat liver, pig liver, S. cerevisiae, and C. albicans microsomes, with an I50 varying from 3 to 5 microM. Both E and Z isomers were inactive on squalene epoxidase at the higher concentrations tested.     

滇杨中三萜成分的研究

滇杨(Populus yunnanensis Dode)又名云南白杨,为杨柳科(Salieaceae)杨属植物,该属植物约有100多种,广泛分布于欧,亚、北美诸洲,我国约有62种,分成5组,滇杨属青杨组(Sect.Tacamahaca Spach)。杨属系速生树种,近年因绿化和改造自然而受重     

Preparation and evaluation of carborane analogues of tamoxifen

A stereoselective synthesis of closo carborane analogues of tamoxifen was developed where the products represent a new approach to developing metabolically robust SERMs. The A-ring found in the backbone of tamoxifen was replaced with an ortho carborane cluster; the product was determined to be the desired Z isomer, which showed superior chemical stability to tamoxifen both in solution and in the solid state. By use of microwave heating, it was possible to convert some of the Z carborane tamoxifen analogue to the corresponding E isomer. Cell growth assays using both isomers and a carborane that is known to target the ER were conducted using estrogen receptor (ER) positive and ER negative human breast cancer cells with and without the presence of estradiol (E2). The Z carborane isomer was able to inhibit cell proliferation better than tamoxifen in an E2 free environment, while the E isomer inhibited cell growth better than tamoxifen when E2 was present.     

毛茛甙全合成的研究

本文报道用天然D-甘露醇为原料,合成了天然(-)毛茛甙。用NaIO_4或Pb(OAc)_4氧化1,2;5,6-二缩丙酮甘露醇(3),得到所需的2,3-缩丙酮-D-甘油醛(4)。经Wittig反应得到以顺式异构体(7)为主的产物。考察了不同溶剂对该反应立体化学的影响。建立了测定及分离顺、反异构体的方法。7在酸催化下水解并环合得光活的毛茛甙元(8),8与溴代乙酰葡萄糖缩合,再经阳离子交换树脂催化水解除去乙酰保护基,完成了天然毛茛甙立体选择性合成。从原料甘露醇经各中间产物均按重结晶产品计算,总收率达15%。     

Antifungal Activity of the Essential Oils of Nine Zingiberaceae Species

The rhizome oils of nine Zingiberaceae species [Zingiber officinale Rosc., Z. cassumunar Roxb., Z. zerumbet Smith, Curcuma aeruginosa Roxb., C. mangga Valeton and van Zyp, C. xanthorrhiza Roxb., Kaempferia galanga Linn., Alpinia galanga Swartz and Boesenbergia pandurata (Roxb.) Schlecht] were investigated for their antifungal activities against five dermatophytes (Trichophyton mentagrophytes, T. rubrum, Microsporum canis, M. nanum and Epidermophyton floccosum), three filamentous fungi (Aspergillus niger, A. fumigatus and Mucor sp.) and five strains of yeast (Saccharomyces cerevisiae, Cryptococcus neoformans, Candida albicans, Ca. tropicalis and Torulopsis glabrata). The antifungal testing was carried out by using the broth microdilution and the disc gel diffusion methods. Amongst the essential oils studied, only the oil of B. pandurata was effective against all the fungi, exhibiting the lowest MIC values of 0.63µgµl -1 to Mucor sp., 1.25µgµl -1 to both A. niger and A. fumigatus, and 2.5µgµl -1 to both T. rubrum and E. floccosum, and the highest inhibition zone diameter of 20.6mm against S. cerevisiae. The essential oil of K. galanga showed selective toxicity against A. fumigatus with a MIC value of 0.63µgµl -1, while the essential oils of Z. officinale and Z. cassumunar exhibited high activity against the yeasts (11.7-15.7mm). The chemical composition of the active essential oils was investigated by GC and GC-MS.