肉豆蔻酸单萜醇酯对布南色林经皮透过的影响

本文以环状单萜醇α-萜品醇、L-薄荷醇及链状单萜醇香叶醇、香茅醇为先导化合物,采用酰氯酯化法合成肉豆蔻酸α-萜品醇酯(TER-C14)、肉豆蔻酸-L-薄荷醇酯(MEN-C14)、肉豆蔻酸香叶醇酯(GER-C14)和肉豆蔻酸香茅醇酯(CIT-C14),并考察单萜醇及其肉豆蔻酯作为促透剂对布南色林(Blo)的促透效果。通过体外经皮渗透实验、体外释放实验和分子模拟技术初步探究单萜醇及其肉豆蔻酯的促透机制。结果显示,当GER-C14或CIT-C14为促透剂时,均有显著的促透效果(P<0.05),并且24h经皮累积透过量是空白组的4.84倍和4.45倍。促透机制为肉豆蔻酸单萜醇酯破坏药物与神经酰胺之间的氢键相互作用,增加脂质迁移率和药物的自由能,从而促进药物的渗透。肉豆蔻酸单萜醇酯有望作为新型促透剂在经皮给药系统中广泛应用。     

立体异构单萜醇油酸酯的制备及促透活性评价

本文以互为立体异构体的香叶醇(GER)、橙花醇(NER)为先导化合物,采用酰氯酯化法合成油酸香叶醇酯(GER-dC18)、油酸橙花醇酯(NER-dC18),并考察GER、NER、GER-dC18、NER-dC18作为促透剂对多奈哌齐(DNP)的促透活性差异。通过体外释放试验、红外光谱法和分子模拟技术初步探究其促透机制,结果发现,所选用促透剂不仅能够促进DNP从压敏胶中释放,而且能够作用于角质层脂质及角蛋白并促进水合作用来降低角质层的屏障功能,从而增加DNP的经皮透过。其中,(E)构型的GER-dC18对DNP具有最优的促透效果,有望为经皮制剂的开发提供关键的辅料。     

丙氨酸酯衍生物的合成及其对吲哚美辛的经皮促渗活性

以N,N-二乙基-l-丙氨酸为原料,N,N′-二环己基碳二亚胺为缩合剂,4-甲氨基吡啶为催化剂,合成了7个新型的2-(N,N′-二乙基氨基)丙酸酯（1a~1g）,其结构经¹H NMR, MS（ESI）和元素分析表征。研究了其对药物吲哚美辛的体外经皮促渗活性。结果表明：1g对吲哚美辛的经皮促渗活性最好（94.2%）。     

乌龙茶“铁观音”香气成分的气相色谱/质谱分析

以HP-20M（50m×0.2mm×0.2μm）毛细管柱为分离柱,GC/MSD分析中国乌龙茶“铁观音”的香气成分,结果表明,“铁观音”茶的香气主成分为沉香醇及其氧化物、苯甲醛、3-己烯醇己酸酯、3-甲基丁酸、α-萜品醇、水杨酸甲酯、己酸、牛儿醇、苯甲醇、苯乙醇、苯乙腈、顺-茉莉酮、4-甲基-3-乙基吡咯、β-紫罗酮、橙花叔醇、癸醇己酸酯、顺-法呢醇和吲哚等。     

4-(N-乙基-3-甲基苯胺基）丁酸甲酯的合成

以γ-丁内酯为起始原料,经开环氯化和醇解反应合成4-氯丁酸甲酯（2）; 2与N-乙基间甲苯胺经亲核取代反应合成了4-(N-乙基-3-甲基苯胺基）丁酸甲酯,纯度97.5%,总收率75.3%,其结构经¹H NMR确证。     

聚乙烯醇／壳聚糖共混膜优先透醇性能的研究

聚乙烯醇／壳聚糖共混膜优先透醇性能的研究王新平，沈之荃，张富尧，林荣轩（浙江大学高分子系，化学系，杭州，３１００２７）关键词渗透蒸发，聚乙烯醇／壳聚糖共混物膜，乙醇水溶液本文首次报道利用亲水性的聚乙烯醇和壳聚糖制得具有很高的乙醇优先透过选择性的透醇型...     

RP-HPLC法分离和测定荆花胃康原料药和胶丸中的对-异丙基甲苯和α-萜品烯

建立了分离和测定荆花胃康原料药和胶丸中的主要成分对-异丙基甲苯（ρ-cymene）和α-萜品烯（α-Terpinene）的反相高效液相色谱梯度洗脱的方法.采用Spherisorb ODS1分析柱;甲醇-水梯度洗脱：0～15 min（V（甲醇）：V（水）=75：25）,15～22 min（V（甲醇）：V（水）=85：15）,22～28 min（V（甲醇）：V（水）=75：25）;紫外检测波长220 nm.对-异丙基甲苯在2.0～6.0 mg/mL,α-萜品烯在4.0～12.0 mg/mL范围内,峰面积与其质量浓度呈良好的线性关系;平均加样回收率对-异丙基甲苯为99.6%（RSD=1.3%）,α-萜品烯为98.2%（RSD=1.1%）.该方法灵敏度高,重现性好,结果稳定,可用于同时测定荆花胃康原料药及胶丸中的对-异丙基甲苯和α-萜品烯.     

N,N-二取代甘氨酸酯的合成及其经皮促渗活性

合成了4个新的N,N-二取代甘氨酸酯,其结构经^1HNMR谱、IR谱、MS-ESI谱和元素分析确证。在改良的Franz扩散池上,用离体裸鼠皮作生物膜,扑热息痛或消炎痛作药物模型进行经皮促渗活性对比试验。结果显示：N,N-二甲基甘氨酸-（E）-3,7-二甲基-2,6-辛二烯酯（2a）具有出色的促透活性,含2．5％的2a促进扑热息痛、消炎痛经皮渗透的效果分别是Azone的2．1和2．6倍,且时滞缩短,超过DDAA的经皮促渗活性;而N,N-二甲基甘氨酸-6-戊氧基-1-己酯（2b）的经皮促渗活性接近Azone,且时滞更短。     

(R)-α-萜品醇的不对称合成

在催化量的手性催化剂存在下，利用１－苯磺酰基－３－丁烯－２－酮与异戊二烯的不对称催化Ｄｉｅｌｓ－Ａｌｄｅｒ反应，合成了（Ｒ）－α－萜品醇５，光学纯度值达到９２％．     

（R）—α—萜品醇的不对称合成

在催化量的手性催化剂存在下，利用１－苯磺酰基－３－丁烯－２－酮与异戊二烯的不对称催化Ｄｉｅｌｓ－Ａｌｄｅｒ反应，合成了（Ｒ）－α－萜品醇５，光学纯度值达到９２％。     

1-(2-Quinoxalyl)-, 1-[3,5-Di(trifluoromethyl)phenyl]-, 1-(2-Carboxyphenyl)-, and 1-Ethoxycarbonyl-4-oxo-4,5,6,7-tetrahydroindazoles

The corresponding 1-(2-quinoxalyl)-, 1-[3,5-di(trifluoromethyl)phenyl]-, and 1-ethoxycarbonyl-3-methyl-4-oxo-4,5,6,7-tetrahydroindazoles have been obtained from reactions of 2-acetyl-1,3-cyclohexanedione, its 5,5-dimethyl and 5-(2-furyl) derivatives, with 2-hydrazinoquinoxaline, 3,5-di(trifluoromethyl)phenylhydrazine, and ethoxycarbonylhydrazine. On interaction with ethoxycarbonylhydrazine the intermediate 2-[1-(-ethoxycarbonyl)hydrazino]ethylidene-1,3-cyclohexanediones were also isolated. From the potassium salt of 2-formyldimedone and 2-carboxyphenylhydrazine hydrochloride, 2-(2-carboxyphenyl)hydrazinomethylene-5,5-dimethyl-1,3-cyclohexanedione was obtained, the cyclization of which in ethanol in the presence of HCl led to 1-(2-carboxyphenyl)- and 1-(2-ethoxycarbonylphenyl)-6,6-dimethyl-4-oxo-4,5,6,7-tetrahydroindazole.     

Synthesis of 1-(alkylamino)- and 1-(dialkylamino)benzimidazoline-2-thiones

Unlike 1-aminobenzimidazoles, 1-alkylaminobenzimidazoles are thiolated on fusing with sulfur without elimination of theN-amino group, yielding the previously unknown 1-(alkylamino)benzimidazoline-2-thiones. These compounds can be more conveniently obtained on a preparative scale by thiolation of 1-alkylacetamidobenzimidazoles with subsequent hydrolytic elimination of the acetyl group. When 1-(dialkylamino)benzimidazoles are fused with sulfur, they are converted into 1-(dialkylamino)benzimidazoline-2-thiones. By alkylation of 1-(methylamino)- and 1-(diethylamino)benzimidazoline-2-thiones with methyl iodide in alkaline media the corresponding 2-(methylthio)benzimidazoles were prepared.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2231–2235, November, 1995.The authors are grateful to the Contest Center of Basic Natural Science at St. Petersburg University for financial support of this study.     

ON THE ANIONS OF DIPHENYL 1-(4-NITROPHENYLAMINO)-1-ARYLMETHANE PHOSPHONATES1

Abstract

By means of UV spectroscopy it is shown that the anions derived of diphenyl 1-(4-nitrophenylamino)-1-arylmethane phosphonates are carbanions and not nitranions. This spectroscopical finding is corroborated by alkylation of the anions to give almost quantitatively the C-alkylated products.     

COPPER-CATALYSED REARRANGEMENT OF 4-SUBSTITUTED-2,3-1H-BENZOXAZINE-1-THIONES

Abstract

4-Substituted-2,3-1H-benzoxazine-1-thiones were prepared by the treatment of the corresponding benzoxazine-1-ones with P₂S₅. The thermal rearrangement of 4-substituted-2.3-1H-benzoxazine-1-thiones, catalysed by metallic copper, yielded 4-substituted-2.3-1 H-benzthiazine-1-ones.     

(Z)-1-[2-(二苯基碘化锡基)乙烯基]-1-环己醇的合成、晶体结构和性质

报道了标题化合物的合成、晶体结构及性质。该晶体属于单斜晶系，空间群为P2~1，晶胞参数a=0.9255(3)nm，b=1.0504(3)nm，c=1.0217(3)nm，β=100.99(2)°，V=0.9750nm^3，Z=2，D~c=1.790g/cm^3，R=0.025，晶体结构由直接法解出。标题化合物分子中的锡原子被配体的三个碳、一个碘和一个氧原子配位；配位原子是畸变的三角双锥构型；标题化合物具有与卤素发生取代反应而不发生加成反应的性质。     

Metabolic study of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone to the enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in vitro in human bronchial epithelial cells using chiral capillary electrophoresis

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) with one chiral center at the carbinol is a major metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). As tobacco specific N-nitrosamines (TSNAs), NNK and NNAL are the most pulmonary carcinogens in tobacco products and smoke. In this paper, a chiral CE method modified with highly sulfated β-cyclodextrin (S-β-CD) was developed to investigate the stereoselective formation of NNAL from NNK in vitro in normal human bronchial epithelial (NHBE) cells. Combined with solid phase extraction (SPE) of the cell samples, NNK and NNAL enantiomers were baseline separated under the proposed CE conditions, with satisfactory recoveries (72.5-113% for NNK and (±)-NNAL) and low limits of detection (LOD, 2.5-3 μg/mL for NNK and (±)-NNAL). The cytotoxicity of NNK in NHBE cells was investigated through the cell counting kit (CCK) assay and proved to be highly dependent on the NNK's concentration. The metabolic results obtained from CE analysis demonstrated that NNK was preferentially metabolized to (+)-NNAL through carbonyl reduction. Meanwhile, the ratio of [(+)-NNAL]/[(-)-NNAL] was independent of NHBE cells' incubation time with NNK, but could be changed according to the original incubation concentration of NNK. This chiral CE method could be useful for the study on toxicology and metabolic transformations of related TSNAs.     

1-[2-(N,N-二甲氨)乙基]-5-巯基-1H-四氮唑的制备与表征

头孢菌素类药物是抗生素发展最为迅速的品种之一.在头孢菌素母体(7-ACA)的C3位修饰含氮化合物是开发长高效型头孢菌素的主要方向,1-[2-(N,N-二甲氨)乙基]-5-巯基-1H-四氮唑是制备新一代口服长效型药物头孢替安脂C3位的化学修饰物[1].     

(Z)-1-[2-(苯基溴氯化锡基)乙烯基]-1-环己醇的晶体结构和反应机理

有机锡化合物的抗癌活性与结构的关系是人们所关注的一个重要课题[1.2].自1989年以来,我们合成了几个系列的C-Sn直接相连并在分子中存在O→Sn内配位的有机锡化合物[3]．经过抗癌活性实验,发现其中有很多种具有较高的抗癌活性．本文所报道的标题化合物分子有两种构型,迄今为止未见类似的报道．标题化合物的抗癌活性正在测试中．1实验部分1．且仪器1106型元素分析仪;锡含量用重量法分析;NicoletR。M／E四圆衍射仪．1．2标题化合物的合成（Z）－l｛2－（二苯基演化锡基）乙烯基11一环己醇（I）按照文献［"方法合成．产率80％,m．卜14…     

2,2-二甲基-1-[5-二茂铁基-3-(三氟甲基)-1H-吡唑-1-基]丙-1-酮的合成及其电化学性质

以乙酰基二茂铁为原料,经3步反应合成了一个新型的二茂铁衍生物——2,2-二甲基-1-[5-二茂铁基-3-(三氟甲基)-1H-吡唑-1-基]丙-1-酮(4),其结构经1H NMR,ESI-MS,元素分析和X-射线单晶衍射表征。4属单斜晶系,P2(1)/c空间群,晶胞参数a=7.805 6(4),b=20.906 1(11),c=11.124 6(6),β=93.820(2)°,V=1 811.33(17)3,Z=4,Dc=1.482 g·cm-3,μ=0.872 mm-1,R1=0.034 8,wR2=0.089 2。采用循环伏安法研究了4的电化学性质。结果表明:4有一对可逆的氧化还原峰,Epa=0.640 V,Epc=0.482 V,ΔE=153 m V。     

Solvent Extraction of Alkaline Earths with 1-Phenyl -3-Methyl 4 Stearoylpyrazol - 5 - One and Topo

Abstract

The synergic extraction of Ca, Sr, and Ba ions from aqueous solutions into cyclohexane or benzene containing 1- pheny 1 - 3 - methyl - 4 - stearoylpyrazol - 5 - one (HPMSP) and TOPO has been studied. Quantitative extraction (log D>2) was attained at pH>5.4 for Ca, pH>6.5 for Sr, and pH>7.3 for Ba when cyclohexane containing 0.05 M HPMSP and 0.01 M TOPO was used, and the corresoponding values for benzene were 6.5, 7.8, and 8.4. Extracted species were M(PMSP)₂(TOPO)₃ (M=Ca, Sr, Ba) for cyclohexane and Ca(PMSP)₂(TOPO)₃ and Sr (or Ba) (PMSP)₂(TOPO)₂ for benzene.