白木香酸晶体结构的研究

白木香酸(C₁₅H₂₄O₃)的晶体属单斜晶系,空间群C2,晶胞参数为:a=12.150(3),b=10.827(4),c=11.344(4),B=111.78(2)°,Z=4,理论密度Dc=1.208 gcm^-3。在“RIGAKU”衍射仪上收集强度数据;用直接法(MULTAN 80)解结构;全矩阵最小二乘修正结构,对2052个衍射点,最终R=0.060;差值Fourier综合确定了氢原子位置。     

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。}     

利用主客体分子包结现象选择分离蛇床子有效成分的方法

利用1,1,6-四苯基-2,4-已二炔-1,6-二醇(I)的包结能力,可简单而迅速地从蛇床子中选择分离出有效成分欧前胡素(2)和花椒毒素(3),收率分别为0.054%(2)和0.002%(3)。本文用UV,IR,¹HNMR和¹³CNMR验证了2和3的化学结构,并用HPLC检验了2和3的纯度。X-射线衍射晶体结构分析表明主体分子I与组分2靠氢键形成包结物,它们的摩尔比为1:2,氢键长为2.8612A。包结物晶体属单斜晶系,空间群为已P₂₁/C,晶胞参数:a=15.468(5)A,b=8.595(3)A,c=18.663(7)A,β=93.64(5)°,Z=4和R=0.088。     

(S)-2-(Boc-氨基)-3-[(S)-2-氧代-3-吡咯烷基]丙酸甲酯单晶制备及其结构表征

目的 培养(S)-2-(Boc-氨基)-3-[(S)-2-氧代-3-吡咯烷基]丙酸甲酯单晶,并进行晶型表征和立体结构确证。方法 用醋酸乙酯-甲基叔丁基醚（1∶1）体系培养单晶,并采用热重法、差示扫描量热法、粉末X射线衍射和单晶X射线衍射分析。结果 制备得到无色块状晶体;样品熔点约为114 ℃;该晶胞属于正交晶系,空间群为P2₁2₁2₁,分子式为C₁₃H₂₂N₂O₅,相对分子质量为286.33,晶体密度为1.152 mg/mm³,绝对构型为S,S构型。结论 确定了(S)-2-(Boc-氨基)-3-[(S)-2-氧代-3-吡咯烷基]丙酸甲酯的立体构型,培养的晶体为非水合物和溶剂化物。     

抗心律失常药物作用的新靶点M3R/IKM3

目的研究心脏M₃受体/M₃受体介导的钾通道与心律失常的关系，寻找抗心律失常药物的新靶点。方法 分别以结扎大鼠左冠状动脉前降支所致急性心律失常模型和膜片钳技术为基础，观察M₃受体的干预作用及作用机制。结果M₃受体阻断剂4DAMP(4-diphenylacetoxy-n-methylpiperidine-methiodide)加重结扎大鼠冠状动脉前降支所致心律失常，而M₃受体激动剂胆碱能明显对抗其作用。其他亚型受体阻断剂，M₁受体阻断剂(prienzepine)、M₂受体阻断剂(methotramine)和M₄受体阻断剂(tropicamide)对结扎大鼠左冠状动脉前降支所致急性心律失常无影响。在膜片钳实验中发现，胆碱可激活一种延迟整流钾电流(IK_M3)，此电流可被M₃受体阻断剂4DAMP明显抑制。而M₁，M₂和M₄受体阻断剂对胆碱介导的电流无作用。结论胆碱通过激动心肌M₃受体诱发一外向钾电流(IK_M3)，并在维持心脏离子通道平衡中起重要作用。M₃受体/IK_M3可能是抗心律失常新靶点。     

6-(4-取代苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物的合成及其抑制血小板聚集的作用

为了寻找较理想的抗血栓药物,本文设计合成了6-(4-取代苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物16个。对ADP诱导的大鼠体外血小板聚集,均有不同程度的抑制作用。其中,化合物Ⅱ₂,Ⅱ3和Ⅱ₄的作用大于CCI-17810,又以Ⅱ₄的作用为最强。     

离子色谱法同时测定葡萄糖酸钙及其杂质(Cl-,SO42-)的含量

本文采用Waters ILC-1离子液相色谱仪,IC-PAK A50×4.6mm色谱柱,pH6.61×10^-3mol/L邻苯二甲酸溶液为流动相,430型电导检测器检测,由外标法和外标单点校正法同时测定了葡萄糖酸钙及其杂质(Cl^-,SO₄^2-)的含量。方法简便、快速,测定结果与中国药典法一致。外标法和外标单点校正法测定Cl^-,SO₄^2-的平均回收率为100.8%和100.2%,相关系数分别为0.9951(n=8)和0.9961(n=8)。     

白三烯C4（LTC4）放射受体结合方法的建立及二苯乙烯低聚体和LTC4受体结合特性

目的：建立LTC₄放射受体结合实验方法,并比较二苯乙烯低聚体（Gn-3）和LTC₄受体的结合特性。方法：以豚鼠肺膜为实验材料,采用³H-LTC₄为放射配体,以FPL₅₅₇₁₂作阳性对照药物,Gn-3为实验药物,进行药物竞争结合实验。采用离体器官生物检测法鉴定Gn-3对LTC₄受体的拮抗作用。结果：3H-LTC₄与其相应受体呈现单一结合位点,Gn-3可明显取代3H-LTC₄与其受体结合。生物学检定法证实Gn-3可抑制LTC₄引起的生物学效应。 结论：豚鼠肺膜LTC₄受体为单一结合位点受体,Gn-3为高活性的LTC₄受体拮抗剂。     

药物透过血脑屏障的3D-QSPR:H2受体拮抗剂的CoMFA和EVA分析

目的：药物透过血脑屏障是药代动力学的重要过程,H₂受体拮抗剂是作用于神经外周的抗溃疡药物,为避免该类药物透过血脑屏障损伤中枢神经,产生毒副作用,指导该类药物的设计与合成。方法和结果：选择了不依赖于实验参数的比较分子力场分析(CoMFA)方法和最近发展的本征值(EVA)方法,建立了有关的三维药代动力学性质(3D-QSPR)模型。CoMFA模型的统计参数为：交叉验证系数r²_cv=0.625,相关系数r2=0.893,F_3,17=47.270,标准偏差SE=0.254;EVA模型的统计参数为：交叉验证系数r²_cv=0.697,相关系数r²=0.922,F_3,17=67.766,标准偏差SE=0.203。结论：两种方法都能建立三维定量构效模型,EVA模型有更高的预测能力。     

Unusual intramolecular hydrogen bonding in cycloamanide A,cyclic (LPro-LVal-LPhe-LPhe-LAla-Gly)

The naturally occurring cyclic hexapeptide, cycloamanide A, has only one intramolecular hydrogen bond. It is a 4 ← 1 type that encompasses the LPhe-LAla sequence in which the experimentally determined ø, ← values are + 54d?, – 118d? and – 88d?, – 4d?, respectively. Even though the chirality is L, L, the ø, ← values are characteristic for a D, L β-bend, Type II°. The conformation of the molecule was established by a crystal structure determination using X-ray diffraction analysis. Cycloamanide A (C₃₃H₄₂N₆O₆←. 4H₂O) crystallizes in space group P2₁2₁2₁ with cell parameters a = 13.307(2) Å, b = 24.820(4) Å and c = 11.231(1) Å.     

Structure and conformation of linear peptides

The tripeptide, glycyl-glycyl-L-valine, crystallizes as a dihydrate in the monoclinic space group P₂1, with a = 5.786(1), b = 7.954(2), c = 14.420(3)A, β= 93.85(2)d?, Z = 2. The structure was solved by direct methods and refined to an R-value of 0.040 for 876 observed reflections. The molecule exists as a zwitterion in the crystal. The peptide planes show significant deviations from planarity. The chain conformation resembles a reverse turn if the orientation of the carboxyl group is also taken into account. An intramolecular water bridge links the amino and carboxyl ends of the molecule. The crystal packing involves spatial segregation of polar and nonpolar moieties.     

Photometric study on the reaction between 2,3,7,8,12,13,17,18-octabromo- 5,10,15,20-tetrakis-(4-methylpyridyl) porphine and various metal ions

The chelate forming reaction between 2,3,7,8,12,13,17,18-octabromo-5,10,15,20-tetrakis(4-methylpyridyl)porphine (OBTMPyP) and various metal ions, which belong mainly to 4th period and 7th-12th groups in the periodic table, was examined by the observing the absorption spectra. Because one chemical spicy, H-OBTMPyP, which is one protonated compound at an N atom of pyroll ring among 4 pyroll rings, was observed at pH 9.0, this pH was used to measure the changes of absorption spectra with metal ions. From these changes of absorption spectra of OBTMPyP with metal ions, OBTMPyP were seen to react easily with Cu2?, Zn2?, Mn2?, or Co2? ion without other additional reagent or heating within 1 min at over 25 °C. On the other hand, OBTMPyP reacted little with Ni2?, and was not all with Fe3? (or Fe2?) reduced by ascorbic acid from Fe3?) under the same conditions. 5,10,15,20-tetrakis(4-methylpyridyl)porphine (TMPyP) also did not reacted metal ions above these conditions. The λ(max) of each Soret band differed. The stability constants (Ka value) of Cu-, Zn-, Mn- and Co-OBTMPyP was calculated by the change in absorbance of each band, and was 2.6 × 10?, 3.6 × 10?, 2.7 × 10? and 2.9 × 10? (dm3/mol), respectively. It was revealed that OBTMPyP and metal ions reacted at molar ratio of 1:1, and octabromination of porphine rings improved the reactivity with these ions.     

Structure and conformation of peptides involving prolyl residue III. L-Prolyl-L-isoleucine monohydrate

The dipeptide, L-prolyl-L-isoleucine monohydrate (C₁₁ H₂₀N₂O₃· H₂O, molecular weight 246.3) crystallizes in the monoclinic space group P2₁, with a = 6.601(3)Å, b = 5.413(3) Å, c = 19.128(6) Å, β= 98.1(1)°, Z = 2, Do = 1.20g·cm^-3 and Dc = 1.208g·cm^-3. The structure was solved by MULTAN–80 and refined to a final R-factor of 0.081 for 594 reflections measured on a Enraf Nonius CAD-4 diffractometer. The peptide linkage exists in the trans conformation. The pyrrolidine ring is disordered with two alternate envelope conformations for the C^γ atom. The values of the sidechain torsion angles are: χ₁₁=– 63.6(17)°, χ₁₂= 171.1(16)° and χ₂=– 59.6(21)° for isoleucine (C-terminal). The crystal structure is stabilized by a three-dimensional network of N—H ? O, O—H ? O and C—H ? O hydrogen bonds. The dipeptide exists in the extended Conformation.     

Function of K⁺-Cl⁻ cotransporters in the acid secretory mechanism of gastric parietal cells

Gastric proton pump (H?, K?-ATPase) secretes H? of acid (HCl) via the luminal membrane of parietal cells. For the HCl secretion, Cl?- and K?-transporting proteins are required. Recent our studies have demonstrated that K?-Cl? cotransporters (KCC3a and KCC4) are expressed in gastric parietal cells. KCC3a is associated with Na?, K?-ATPase in the basolateral membrane, and KCC4 is associated with H?, K?-ATPase in the apical canalicular membrane. This paper summarizes the functional association between KCCs and P-type ATPases and the contribution of these complexes to acid secretion in gastric parietal cells.     

Structural elucidation of a new flavone from Sarcopyramis nepalensis

A novel flavone, named 4′-methoxy-3′,5,7-trihydroxy-8-(1″-(3?,4?,5?-trihydroxyphenyl)ethyl)flavone (1), was isolated from Sarcopyramis nepalensis, along with two known compounds syringaresinol (2) and aralidioside (3). Their structures were established by the spectroscopic analysis, especially by 2D NMR. All of the three compounds were isolated from the plant for the first time.     

Crystal structure and surface properties of an investigational drug--a case study

In this study we investigate the correlations between the single crystal structure, the crystal habitat and morphology, and surface energetics of an investigational pharmaceutical compound. Crystal structure of this investigational pharmaceutical solid has been solved from single crystal X-ray analysis. Crystallographic data are as follows: triclinic, P1 (no. 1), a = 6.1511 (8) Å, b = 13.5004 (18) Å, c = 17.417 (2) Å, = 68.259 (2)°, β = 80.188 (2)°, γ = 82.472 (2)°, V = 1320.2 (3) ų, Z = 2. The external morphology of this crystalline solid was predicted by molecular modelling using attachment energies to be thin-plate like with a dominant face (0 0 1). The predicted morphology was confirmed by scanning electron micrographs (SEM) and the Miller Index of the dominant face was complemented by X-ray powder diffraction (XRPD) method. The microscopic layering structures of crystals and surface stability of the dominant faces were investigated using atomic force microscopy (AFM). Contact angle measurement showed that the surface of the dominant face is hydrophilic as predicted from crystal structure.     

软珊瑚共附生真菌Schizophyllum sp. CGF9-1-2次生代谢产物研究

目的 首次对软珊瑚来源共附生裂褶菌属真菌Schizophyllum sp. CGF9-1-2次生代谢产物的化学成分进行研究,以期获得结构新颖、生理活性好的次生代谢产物。方法 以PDA及真4培养基发酵软珊瑚共附生真菌Schizophyllum CGF9-1-2;采用硅胶、凝胶、ODS等柱层析、高效液相色谱法（HPLC）等方法对其菌丝体的乙酸乙酯部位进行分离纯化;采用核磁共振（NMR）、（高分辨）质谱（（HR）MS）和旋光（ORD）等现代波谱解析手段,并与文献数据对照方法确定化合物结构。结果 从其乙酸乙酯部位共分离鉴定10个化合物,依次为7, 8-二甲基四氧嘧啶（1）、杂色曲霉素（2）、Arugosin C（3）、酒酵母甾醇（4）、（22e,24r）-3β, 5α, 9α-三乙烯基麦角甾-7, 22-二乙烯-6酮（5）、1-亚油酸甘油酯（6）、10-十七烯酸甲酯（7）,2-辛烷烯酸甲酯（8）、十八烷酸（9）和十四烷酸（10）。结论 首次从裂褶菌属真菌CGF9-1-2中分离鉴定10个化合物,结构类型涉及吡嗪类、芳香酚酸类和长链脂肪酸及酯类。丰富了宿主软珊瑚中海洋微生物的种类,确定其次生代谢产物的多样性,为进一步药理活性实验奠定了基础。     

桥环黄皮酰胺差向异构体的结构研究

目的研究桥环黄皮酰胺差向异构体的结构。方法用单晶X-射线衍射分析法测定了从植物黄皮提取物中分离得到的化合物I和采用合成方法得到的化合物III的晶体结构,并用分子力学计算方法分别模建化合物II和IV的立体结构。结果化合物I和III的分子式均为C₁₈H₁₇O₂N,计算分子量为279.34,其中化合物I属单斜晶系,空间群为P2₁;化合物III属三斜晶系,空间群为P1。结论化合物I和III均为桥环黄皮酰胺,但在C₆位苯环的取向不同。桥环黄皮酰胺可形成4对差向异构体,而苯环取向对自由态分子能量影响不大。     

Isolation and characterization of a new iturinic lipopeptide, mojavensin A produced by a marine-derived bacterium Bacillus mojavensis B0621A

Three lipopeptides were isolated by bioactivity-guided fractionation from the fermentation broth of Bacillus mojavensis B0621A. A new iturinic lipopeptide, named mojavensin A, was tentatively characterized by 1D, 2D NMR and MS spectroscopy, Marfey's method containing a novel peptide backbone of L-Asn?, D-Tyr?, D-Asn?, L-Gln?, L-Pro?, D-Asn?, L-Asn? and an anteiso-type of the saturated β-fatty acid side chain. Compound 2 and 3 were tentatively identified as iso-C16 fengycin B and anteiso-C17 fengycin B, respectively. These lipopeptides displayed dose-dependent antifungal activity against a broad spectra of phytopathogens and were weakly antagonistic to Staphylococcus aureus. Moreover, they all revealed cytotoxic activities against the human leukemia (HL-60) cell line. Mojavensin A, iso-C16 fengycin B, and anteiso-C17 fengycin B inhibited the growth of HL-60 with IC?? of 100, 100 and 1.6?μM, respectively.