中华大蟾蜍皮化学成分研究

从中华大蟾蜍 (BufobufogargarizansCantor)皮水溶性部分应用制备型反相HPLC分离得到 5个化合物 ,根据光谱分析、氨基酸分析及化学性质 ,确定为蟾蜍灵 3 丁二酰精氨酸酯 (Ⅰ )、华蟾毒精 3 丁二酰精氨酸酯 (Ⅱ )、脂蟾毒配基 3 丁二酰精氨酸酯 (Ⅲ )、蟾蜍噻咛 (Ⅳ )、光色素(Ⅴ ) ;其中Ⅳ、Ⅴ为首次从该属动物中得到 ;并提出了蟾蜍毒素和蟾毒配基在13 C NMR谱中C 16位取代情况的化学位移特征     

美洲蟾蜍皮中一种新类型蟾蜍毒的分离和鉴定

本文报道应用硅胶柱层析、高压液相层析和Sephadex LH-20凝胶层析,从美洲蟾蜍(Bufo americanus)皮中分离得二个新的蟾蜍毒,并经降解和合成研究确定了它们的结构为3-辛二酰-L-谷酰胺海蟾蜍精酯(Ⅳ)和3-辛二酰-L-谷酰胺远华蟾蜍精酯(Ⅸ),这是第一次报道所含的氨基酸为谷酰胺而非精氨酸的天然蟾蜍。     

中药大血藤的酚性化合物

目的对中药大血藤干燥藤茎的化学成分进行研究。方法采用现代色谱技术分离化合物，运用现代波谱技术(IR，MS，¹H NMR，¹³C NMR，²DNMR)对所得化合物的结构进行鉴定。结果从大血藤的藤茎中分得10个酚类化合物，分别鉴定为1-O-(香草酸)-6-(3″,5″-二-O-甲基-没食子酰基)-β-D-葡糖苷(I)、(-)-表儿茶素(II)、阿魏酸-对羟基苯乙醇酯(III)、3-O-咖啡酰奎宁酸(IV)、3-O-咖啡酰奎宁酸甲酯(V)、罗布麻宁(VI)、香草酸(VII)、原儿茶酸(VIII)、3,4-二羟基-苯乙醇(IX)、4-羟基-苯乙醇(X)。结论化合物I为新化合物，化合物III～VI和VIII～X为首次从该植物中分得。     

毒性中药蟾酥质量检测方法研究

目的:建立蟾蜍中多种药效及毒性成分蟾蜍毒素的定性定量检测方法。方法:采用液相色谱-质谱/质谱联用方法检测蟾酥中多种蟾蜍毒素成分。结果:建立了华蟾毒它灵、蟾蜍灵、华蟾毒配基及脂蟾毒配基的LC-MS/MS检测方法。比较了蟾酥样本的液相色谱-质谱/质谱联用分析数据。对4个不同来源中华大蟾蜍及黑眶蟾蜍的蟾酥样本进行检测,检出华蟾毒它灵、蟾蜍灵、华蟾毒配基及脂蟾毒配基的含量范围为0.05%~5.12%(w/w)。结论:液相色谱-质谱/质谱联用方法可用于蟾酥定性定量检测,并为质量评价提供参考。     

海南冬青中的一个新三萜甙

从冬青科植物海南冬青(Ilex hainanensis Merr.)的叶中分离得一新的△¹²-齐墩果叶-烷型的三萜酯甙,甙元的结构为齐墩果叶12-烯23α,28β-二酸3β,16α-二羟基(olean-12-23α,28β-dioic acid 3β,16α-dihydroxyl,Ⅱ),甙的结构为Ⅱ的β-D-葡萄糖(1′→28)酯(β-D-glucopyranosyl(1′→28)ester of Ⅱ),命名为海南冬青甙(hainanenside,Ⅰ)。     

栾树的化学成分

目的：分离鉴定栾树(Koelreuteria paniculata Laxm)叶的化学成分。方法：95%工业EtOH浸提,硅胶柱色谱分离,IR,MS,UV,1HNMR,¹³CNMR等方法确定结构。结果：分得14个化合物,分别为对-二没食子酰乙酯(ethyl-p-digallate)(1),间二没食子酰乙酯(ethyl-m-digallate)(2),对-二没食子酸(p-digalloyl acid)(3),间-二没食子酸(m-digalloyl acid)(4),2″-没食子酰基槲皮素苷(quercitrin-2″-gallate)(5),没食子酸(galloyl acid)(6),没食子酸乙酯(ethyl galloyl acid)(7),鞣花酸(ellagic acid)(8),槲皮苷(quercitrin)(9),金丝桃苷(hyperin)(10),山奈酚-3-O-鼠李糖苷(kaempferol-3-O-rhamnoside)(11),2″-没食子酰金丝桃苷(hyperin-2″-gallate)(12),β-谷甾醇(β-sitosterol)(13),β-谷甾醇-3-O-葡糖苷(β-sitosterol 3-O-gluceroside)(14)。结论：对-二没食子酰乙酯(ethyl-p-digallate)(1),间二没食子酰乙酯(ethyl-m-digallate)(2),对-二没食子酸(p-digalloyl acid)(3)为新化合物,化合物4,5,8～12和14系首次从该植物中分得。并首次系统归属其波谱信号。     

一种新的蟾蜍毒素:海蟾蜍精-3-辛二酰-L-谷酰胺酯

蟾蜍毒素通常是甾体配基的3-位羟基与辛二酰基精氨酸酯侧链结合。近来发现几种带有新侧链的毒素,如代替辛二酰基的有丁二酰基,己二酞基和庚二酰基等。这几种酰基通常又与精氨酸结合。本文报道另一种新型的毒素,其侧链是辛二酰基-L-谷酰胺,而不是精氨酸,这种带有L-谷酰胺基的蟾蜍毒素,在自然界还是首次发现。分离方法:10只美洲蟾蜍(Bufo americanus)以干冰冷冻后剥皮,并立即用乙醇提取,顺次经硅胶柱层,制备薄层和萄萄糖凝胶LH-20分离纯化,得到5毫克新蟾蜍毒素(Ⅱ),熔点166～170°(分解),[α]_D~(20)+15.1°,无     

几种国产药用紫草中萘醌色素的分析

从新疆软紫草石油醚提取物中分离出六个化合物。根据其理化常数、光谱数据(MS,IR,¹HNMR)鉴定为去氧紫草素(deoxyshikonin),β,β-二甲基丙烯酰阿卡宁(β,β-dimethylacryalkannin),乙酰紫草素(acetylshikonin),β-乙酰氧基异戊酰阿卡宁(β-acetoxyisovalerylalkannin),紫草素(shikonin),β-羟基异戊酰阿卡宁(β-hydroxyisovalerylalkannin)。用高效薄层层析扫描方法,分析了我国不同种类、不同产地的紫草根,均含萘醌类色素,但种间含量差异甚大。     

异叶梁王茶甙Ⅲ和Ⅳ的结构

继前报后,又从异叶梁王茶[Nothopanax davidii(France)Harms]树皮中分离得到两种五环三萜皂甙。经化学和波谱(IR,¹HNMR,~(13)CHMR,¹H-¹HCOSY,¹³C-¹H COSY,MS)分析,分别鉴定为3-O-α-(2’,4’-O-二乙酰基)-L-吡喃阿拉伯糖-3β-羟基齐墩果-12-烯-28,29-双羧酸-28-O-[α-L-吡喃鼠李糖(1-4)-β-D-吡喃葡萄糖(1—6)-β-D-吡喃葡萄糖]酯甙(Ⅲ),命名为异叶梁王茶甙Ⅲ和3-O-β-(2-O-乙酰基)-D-吡喃木糖-3β-羟齐墩果-12-烯-28,29-双羧酸甙(Ⅳ),命名为异叶梁王茶甙Ⅳ。这两种皂甙均系首次从植物中分出的新化合物。     

蟾酥缓释微丸的质量标准

目的 研究并制定蟾酥缓释微丸的质量标准。方法 采用TLC鉴别制剂中各成分;采用HPLC分别测定华蟾酥毒基及酯蟾毒配基的含量;采用紫外分光光度计测定制剂中吲哚生物碱类成分。结果 3批制剂均出现与对照品相对应的斑点,阴性制剂无干扰;华蟾酥毒基在0.018 4~0.570 4 μg内呈良好线性关系(r=0.999 8,n=6),平均加样回收率为100.46%,RSD为3.08%(n=9);酯蟾毒配基在0.007 8~0.241 8 μg内呈良好线性关系(r=0.999 8,n=6),平均加样回收率为98.28%,RSD为2.22%(n=9)。初步确定3批样品中华蟾素毒基与酯蟾毒配基的总量不得<0.006 g·g^-1,吲哚生物碱类含量不得<0.007 g·g^-1。结论 本法专属性强、简便可行,可作为蟾酥缓释微丸的质量标准。     

云南甘草中新三萜皂甙元的结构鉴定

从云南甘草(Glycyrrhiza yunnanensis)根中分离出10个化合物。本文报道其中二个新三萜皂甙元,云南甘草皂甙元A和B(glyyunnansapogenin A and B),以及已知化合物β-谷甾醇的鉴定。云南甘草皂甙元A和B的结构经衍生物制备,红外,核磁共振氢谱、碳谱和质谱等光谱测定和解析、分别推定为3β,24-dihydroxy-16-oxo-olean-12-en-29-oic acid和3β,21α,24-trihydroxy-olean-12-en-30-oic acid。     

无纹紫背苔化学成分的研究

目的　研究苔纲植物无纹紫背苔（Plagiochasm intermedium L.）的化学成分。方法　用95%的EtOH回流提取,所得浸膏分部萃取后经硅胶柱及Sephadex LH-20柱色谱反复分离纯化,并用1DNMR,2DNMR及X-ray单晶衍射等技术对化合物的结构进行鉴定。 结果　从无纹紫背苔中分离到6个化合物,分别鉴定为：双联苄类化合物Pakyonol（I）, 24-乙基胆甾-5,22-二烯-3β-软脂酸脂（24-ethylcholesta-5,22-dien-3β-ol-palmitic acid ester,II）, 22-羟基何伯烷（22-hopanol,III）, β-谷甾醇（β-sitosterol, IV）,胡萝卜苷（daucosterol,V）,甘露醇（mannitol,VI）。 结论　II为新化合物, 其余化合物为首次从该属植物中分离得到。     

藏药独一味根环烯醚萜甙的研究

继前报从藏药独一味(Lamiophlomis rotata Kudo)根的正丁醇提取物中首次分离得到4个环烯醚萜甙。根据光谱分析和化学方法鉴定为:8-O-乙酰山栀甙甲酯(I),6-O-乙酰山栀甙甲酯(I),Penstemoside(II)和7,8-dehydropenstemoside(IV),后者为一新化合物。     

马缨丹根的化学成分研究

从马缨丹(Lantana camara L.)根的乙醇提取物中分离鉴定出六个寡糖(Ⅰ～Ⅵ)和六个环稀醚萜葡萄糖甙(Ⅶ～Ⅻ),即水苏糖(Ⅰ),毛蕊花糖(Ⅱ),筋骨草糖(Ⅲ),毛蕊花四糖(Ⅳ),α-D-半乳糖-(1[→6-)α-D-半乳糖-(1]₃→6-)D-葡萄糖(Ⅴ),α-D-半乳糖-(1[→6-)α-D-半乳糖-(1]₄→6-)D-葡萄糖(Ⅵ),黄夹子苦甙(Ⅶ),8-表马钱素(Ⅷ),山栀子甙甲酯(Ⅸ),黄夹苦甙(Ⅹ),lamiridoside(Ⅺ)和京尼平甙(Ⅻ)。Ⅴ和Ⅵ是新化合物,分别命名为马缨丹糖A(lantanose A)和马缨丹糖B(lantanose B),其余均首次从该植物中分离得到。     

野木瓜甙YM10和YM12的结构

从野木瓜(Stauntonia chinensis DC.)中分离得到二个去甲五环三萜皂甙化合物,经化学和光谱分析,分别鉴定为3-O-α-L-吡喃鼠李糖-(1→2)-α-L-吡喃阿拉伯糖-30去甲齐墩果-12,20(29)-二烯-28-羧酸-28-O-α-L-呲喃鼠李糖-(1→4-β-D-吡喃葡萄糖-(1→6)-β-D-吡喃葡萄糖酯,命名为野术瓜甙YM10(Ⅰ)和3-O-α-L-呲喃鼠李糖-(1→2)-α-L-吡喃阿拉伯糖-30-去甲齐墩果-12,20(29)-二烯-28-羧酸-28-O-β-D-吡喃葡萄糖-(1→6)-β-D-吡喃葡萄糖酯,命名为野木瓜甙YM₁₂(Ⅱ)。Ⅰ和Ⅱ均系首次从植物中得到的新化合物。     

异叶梁王茶化学成分的研究

从异叶梁王茶[Nothopanax davidii(Franch)Harms]树皮中分离得到两种五环三萜皂甙,经化学和光谱(IR,¹HNMR,¹³CNMR,¹H-¹H COSY,¹H-¹³C COSY,NOESY,MS)分析,分别鉴定为3-O-α-(3′,4′-O-二乙酰基)-L-吡喃阿拉伯糖-β-羟齐墩果-12-烯-28,29-双羧酸-28-O-[α-L-吡喃鼠李糖(1→6)-β-D-吡喃葡萄糖(1→4)-β-D-吡喃葡萄糖]酯甙(Ⅱ)和3-O-α-(3′-O-乙酰基)-L-吡喃阿拉伯糖-3β-羟齐墩果-12-烯-28,29-双羧酸甙(Ⅱ),前者命名为异叶梁王茶甙Ⅰ,后者命名为异叶梁王茶甙Ⅱ。这两个皂甙均系新化合物。     

Small molecule inhibitors of dynamin I GTPase activity: development of dimeric tyrphostins

Dynamin I is a GTPase enzyme required for endocytosis and is an excellent target for the design of potential endocytosis inhibitors. Screening of a library of tyrphostins, in our laboratory, against the GTPase activity of dynamin I gave rise to a microM potent lead, 2-cyano-3-(3,4-dihydroxyphenyl)thioacrylamide (1, IC50 70 microM). Our initial investigations suggested that only the dimeric form of 1 displayed dynamin I GTPase inhibitory activity. Subsequent synthetic iterations were based on dimeric analogues and afforded a number of small molecules, low microM potent, inhibitors of dynamin I GTPase, in particular, symmetrical analogues with a minimum of two free phenolic -OHs: catechol-acrylamide (9) (IC50= 5.1 +/- 0.6 microM), its 3,4,5-trihydroxy congener (10) (IC50= 1.7 +/- 0.2 microM), and the corresponding 3-methyl ether (11) (IC50= 9 +/- 3 microM). Increasing the length of the central alkyl spacer from ethyl to propyl (22-24) afforded essentially identical activity with IC50's of 1.7 +/- 0.2, 1.7 +/- 0.2, and 5 +/- 1 microM, respectively. No decrease in activity was noted until the introduction of a hexyl spacer. Our studies highlight the requirement for two free amido NHs with neither the mono-N-methyl (86) nor the bis-N-methyl (87) analogues inhibiting dynamin I GTPase. A similar effect was noted for the removal of the nitrile moieties. However, modest potency was observed with the corresponding ester analogues of 9-11: ethyl ester (90), propyl ester (91), and butyl ester (92), with IC50's of 42 +/- 3, 38 +/- 2, and 61 +/- 2 microM, respectively. Our studies reveal the most potent and promising dynamin I GTPase inhibitor in this series as (22), which is also known as BisT.     

刺楸根皮中皂甙的化学成分研究

从刺楸Kalopanox septemlobus(Thunb.)Koidz.根皮中,分离到两个皂甙单体。经光谱(IR,NMR,FAB-MS)分析和化学方法鉴定为刺楸皂甙A(kalopanax saponin A,Ⅰ)和一新的三萜皂甙,结构为3-O-(a-L-吡喃鼠李糖(1→2)-α-L-吡喃阿拉伯糖)-常春藤皂甙元-28-O-[α-L-吡喃鼠李糖(1→2)-β-D-吡喃葡萄糖(1→6)-β-D-葡萄糖]酯甙,命名为刺楸皂甙C(kalopanax saponin C,Ⅱ)。     

Synthesis of 3-hydroxy-3-cyclohexylbutyric acid derivatives. 1. Cyclic homologues of 3-hydroxy-3-methylglutaric acid

Z and E isomers of 3-methyl-3-(carboxymethyl)hexahydro-1 (3H)-isobenzofuranones (I), lactones of 3-hydroxy-3-(2-carboxycyclohexyl) butyric acids (II), were prepared and tested on cholesterol biosynthesis in vitro. Compound I of the Z series was prepared through its ethyl ester by hydrogenation, over Rh/Al2O3 catalyst, of the phenyl ring of 3-methyl-3-[(ethoxycarbonyl)methyl]-1(3H)-isobenzofuranone. Compound I of the E series was prepared, through its ethyl ester, by Reformatsky reaction from ethyl (E)-2-acetylcyclohexanecarboxylate. 3-Methyl-3-(carboxymethyl)-5,6,7,8-tetrahydro-1(3H)-isobenzofuranone, 3-methyl-3-ethyl-5,6,7,8-tetrahydro-1(3H)-isobenzofuranone, and 3-methyl-3-(carboxymethyl)-1(3H)-isobenzofuranone were also prepared and tested. The above compounds inhibited acetate incorporation in cholesterol and fatty acids in rat liver slices at 5 X 10(-3) M but lack specific inhibitory activity on HMG-CoA reductase.     

THE SYNTHESIS OF N-BENZYLOXYCARBONYL-L-PROLYL-DEHYDROPHENYLALANYL-L-HISTIDYL-L-LEUCINE

The direct oxidation of a dipeptide azlactone (1) by DDQ affords an optically active unsaturated dipeptide azlactone (2). It was shown that the double bond had the Z-configuration and that no racemization of the proline moiety occurred during the oxidation. The dehydrotripeptide, Z-Pro-ΔPhe-Phe ˙ OH (9b) was prepared by direct coupling of azlactone (2) with phenylalanine tetramethyl-guanidinium salt and was shown to be stable to chymotrypsin. The tetrapeptide, Z-Pro-ΔPhe-His-Leu ˙ OH (11), was prepared directly from the azlactone (2) and by saponification of the tetrapeptide ester (10) prepared by mixed anhydride coupling of Z-Pro-ΔPhe ˙ OH (7) with the dipeptide ester. The dehydropeptide (11) inhibits angiotensin I converting enzyme (IC₅₀, 1 × 10^-4 M).