几种豆甾醇皂苷的合成

Several stigamasterol saponins were concisely synthesized.Namely,four monosaccharide(glucopyranose,ga-lactopyranose,xylopyranose,2-acetamido-2-deoxy-a-D-glucopyranose),lactopyranose and chacotriose were cou-pled with 3-OH of stigmasterol.All the compounds were identified by NMR,IR and high resolusion MS.     

齐墩果酸衍生物的合成

通过酯化、醚化和酰胺化反应修饰齐墩果酸的3-OH或28-CO2H,合成了26个齐墩果酸衍生物,其中23个未见报道,其结构经1HNMR和MS表征。     

几种齐墩果酸糖缀合物的合成

报道了齐墩果酸与四种单糖和二糖（葡萄糖、半乳糖、乳糖及葡萄糖醛酸）进 行糖苷化制备糖缀合物的方法。在合成过程中首先将葡萄糖、半乳糖及乳糖转化成 相应的全苯甲酰三氯亚胺酯糖基供体（10a-10c），将葡萄糖醛酸转化成为1-溴代 乙酰葡萄糖醛酸甲酯糖基供体（10d）；在齐墩果酸的28-位羧基上进行酰胺化引入 ω-氨基羧酸甲酯得到其衍生物6。然后10a-10c在TMSOTf的催化下与化合物6的3-位 羟基进行β-糖苷化；10d在AgOTf的催化下与6进行β-糖苷化，最后脱掉保护基得 到相应的糖缀合物13a-13d，所有目的化合物均为新化合物，其结构经IR，^1H NMR，^13C NMR，2D-COSY，HMQC，DEPT及HRMS进行了确证。     

活性天然产物和结构多样性类天然产物的合成

天然产物骨架的复杂性和丰富的官能团化赋予了天然产物类化合物独有的生物学活性,因此天然产物作为药物研究的先导化合物有其无法替代的独特性质,比如紫杉醇、红霉素和利福霉素帮助科学家们理解重要的生物过程。以往化学家对天然产物独有情钟,但仅仅以合成天然产物本身为最终目的。今天,化学家们开始利用传统的合成方法来制备结构多样性的类天然产物化合物。这种利用合成手段制备的小分子化合物在生物学的基础研究和药物研究中将起到关键的作用。     

新型齐墩果酸衍生物的合成及其抗肿瘤活性

以齐墩果酸(1)为原料,经3-羟基乙酰化,17-位羧基甲酯化,11-位碳羰基化及光照反应,首次实现了1的10-位角甲基的活化,合成了新型的齐墩果酸衍生物———3β-乙酰氧基-11α-羟基-11,25-环-齐墩果-12-烯-28-酸甲酯(4),其结构经1H NMR,13C NMR,IR和MS表征。采用SRB法测试了1～4及1的衍生物7～9对N-04,Bre-04和Lu-04细胞株的体外抑制活性,结果表明,4,8和9具有明显的抑制肿瘤细胞生长的能力。     

Septemloside III： A Nonasaccharide Saponin from the Bark of Kalopanax septemlobus （Thunb.） Koidz.

A nonasaccharide saponin, new hederagenin saponin, had been isolated from the bark ofKalopanax septemlobus (Thunb.) Koidz., and its structure was elucidated by HRESI-MS, NMR experi-ments and chemical analyses as 3-O-β-D-xylopyranosyl-(1→4)-13-D-xylopyranosyl-(1→3)-α-L-rhamno-pyranosyl-(1→2)-α-L-arabinopyranosyl hederagenin 28-O-β-D-xylopyranosyl-(1→3)-β-D-xylopyra-nosyl-(1→2)-[α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→6)]-β-D-glucopyranoside.     

齐墩果酸乙酰氧基取代三烯的合成及氧化

以齐墩果酸(1)为原料,依次经过17-羧基的甲酯化、3-羟基的苯甲酰化、12-双键的臭氧化、Br2/HBr脱氢、羰基的烯醇乙酰化以及C环的光照开环,得到12-乙酰氧基取代的三烯化合物6。 采用不同的氧化剂,如O3、间氯过氧苯甲酸、H2O2、过氧叔丁醇以及Na2S2O8等对化合物6进行氧化,得到了十氢萘型的手性合成子以及环氧化或者环氧内酯化的齐墩果酸衍生物。     

齐墩果酸衍生物的合成及抗肿瘤活性研究

以天然产物齐墩果酸为先导化合物,经过氧化、酯化(酰化)、水解等反应合成了8个齐墩果酸衍生物,以MCF-7和A549细胞为靶细胞,紫杉醇和吉非替尼为阳性对照物,采用磺酰若丹明B(SRB)法进行初步的体外抗肿瘤活性筛选。结果表明,化合物5a对A549细胞的抑制作用与母体齐墩果酸相当,化合物5d对A549细胞的抑制活性明显高于母体齐墩果酸。因此,化合物5a和5d值得进一步研究。     

新型齐墩果酸糖苷化衍生物的合成及体外抗HCT8活性

为提高齐墩果酸的水溶性和稳定性,以齐墩果酸苷元为起始原料,对其28-COOH进行甲基化修饰后制得齐墩果酸-28-羧甲酯(1)。分别以D-半乳糖、D-葡萄糖、D-氨基葡萄糖为起始原料,通过对糖羟基的保护与去保护,得到一系列的二糖、四糖片段。通过三氯乙酰亚胺酸酯途径和对甲苯硫基途径,利用合成的糖片段对1的3-位羟基进行糖化学结构修饰,合成了4种新型的齐墩果酸糖苷化衍生物(2~5),其结构经1H NMR,13C NMR和MS(ESI)表征。采用MTT法测试了2~5对高表达人结肠癌细胞(HCT8)的体外抑制活性。结果表明:2~5对HCT8有一定的抑制作用,化合物5浓度为1×10^-3 mmol/L时,抑制率达到(98.96±0.10)%。     

Synthesis of an Ursolic Acid Saponin with N-Acetylglucosamine-containing Trisaccharide Residue

The focus of this work is the synthesis of an ursolic acid saponin with an N-acetylglucosamine-containingtrisaccharide residue.Therefore,ursolic acid 3-yl α-L-arabinopyranosyl-(1→2)-α-L-arabinopyranosyl-(1→6)-2-acetamido-2-deoxy-β-D-glucopyranoside(1)was concisely synthesized in convergent synthesis with 48.0% overallyield.The structure of saponin 1 was confirmed by ~1H NMR,~(13)C NMR and mass spectra.     

Synthesis and Tumor Cytotoxicity of Novel N-Substituted Glucosamine-bearing Oleanolic Acid Derivatives

Eleven novel triterpenoid saponins,N-substituted-β-D-glucosaminide derivatives of oleanolic acid,were designed and synthesized via a stepwise glycosylation strategy.These compounds were evaluated for in vitro cytotoxic activity against six different tumor cell lines.Most of the compounds inhibited the growth of,at least,one tumor cell line effectively at micromolar concentrations.Preliminary structure-activity relationships（SARs） indicate that acylation of the nitrogen of the glucosamine-bearing triterpenoid saponins affords the compounds that are highly cytotoxic towards specific tumor cell lines.     

熊果酸与齐墩果酸高效液相色谱分离条件优化

描述了熊果酸、齐墩果酸色谱保留行为与流动相pH和有机溶剂体积分数之间的函数关系,并求解了各自模型中的9个参数,得到在流动相中熊果酸的电离常数pKa=4.8145,齐墩果酸电离常数pKa=4.9317。文章还对模型外推过程中存在的误差进行了校正,并运用校正后的模型预测熊果酸的容量因子,实验值接近预测值,误差小于5%。最后采用熊果酸和齐墩果酸的容量因子与流动相pH和有机溶剂组成之间的函数关系,进行了两者在同一流动相中分离条件的优化,获得了最佳的分离条件:流动相中甲醇体积分数为85.2%,pH为6.50。     

Anti-Cancer Potential of Synthetic Oleanolic Acid Derivatives and Their Conjugates with NSAIDs

Naturally occurring pentacyclic triterpenoid oleanolic acid (OA) serves as a good scaffold for additional modifications to achieve synthetic derivatives. Therefore, a large number of triterpenoids have been synthetically modified in order to increase their bioactivity and their protective or therapeutic effects. Moreover, attempts were performed to conjugate synthetic triterpenoids with non-steroidal anti-inflammatory drugs (NSAIDs) or other functional groups. Among hundreds of synthesized triterpenoids, still the most promising is 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which reached clinical trials level of investigations. The new group of synthetic triterpenoids are OA oximes. The most active among them is 3-hydroxyiminoolean-12-en-28-oic acid morpholide, which additionally improves the anti-cancer activity of standard NSAIDs. While targeting the Nrf2 and NF-κB signaling pathways is the main mechanism of synthetic OA derivatives′ anti-inflammatory and anti-cancer activity, most of these compounds exhibit multifunctional activity, and affect cross-talk within the cellular signaling network. This short review updates the earlier data and describes the new OA derivatives and their conjugates in the context of modification of signaling pathways involved in inflammation and cell survival and subsequently in cancer development.     

新型熊果酸单糖苷的简便合成

以熊果酸为原料,经苄基化反应制得熊果酸苄酯(2); 2与三氯乙酰亚胺酯经糖苷化反应制得酯保护的熊果酸-3-糖苷（4a~4d）;4a~4d依次脱去苄基和苯甲酰基合成了4个熊果酸-3-糖苷(6a～6d,其中6c为新化合物),其结构经¹H NMR, ¹³C NMR和MS(ESI)表征。     

Synthesis of pennogenyl saponins using three methods

The synthesis of pennogenyl saponins using three important methods of glycosylation is reported in this article. Six correlative compounds (7–12) were first synthesized. As donors (1–6), glycosyl halide, trichloroimidate, and thioglycoside were chosen to study their reaction with the acceptor pennogenin. In these reactions the difference in steric hindrance between 3-OH and 17-OH of pennogenin was utilized skillfully and only the 3-hydroxyl group of pennogenin could be connected with each kind of donors selectively. There was no reaction at the 17-hydroxyl group, which had no protection. The characteristic above makes it convenient to synthesize compounds of pennogenyl saponins. Published in Khimiya Prirodnykh Soedinenii, No. 4, pp. 348–350, July–August, 2007.