胍基取代环戊烷衍生物的合成与抗病毒活性研究

目的合成不含羧基的胍基取代环戊烷衍生物并考察羧基的存在与否对化合物抗病毒活性的影响。方法以不含羧基的氨基取代环戊烷为起始原料合成得到目标化合物，并以流感病毒株粤防72．243感染的狗肾细胞为模型对其抗病毒活性进行筛选。结果在测定浓度下所合成的化合物均未显示抗病毒活性。结论不含羧基的氨基取代环戊烷衍生物的胺基被胍基替代后失去抗病毒活性。     

1980年湖北省药剂士晋升药师考核复习提纲辅导材料

1.常用皮质激素类药物化学结构的特点及其与效能的关系。肾上腺皮质激素类药物属类固醇[甾体,Stcroid]化合物,有一共同的基本结构环戊烷多氢菲,其作用与化学结构有密切关系。糖,盐皮质激素具有生理活性的结构特点为固     

含 2-取代-1,3-二硫杂环戊烷席夫碱大环化合物的合成及其抑菌活性研究

目的 开发新型抗菌药物。方法 以不同的β-二酮、二硫化碳、1,2-二溴乙烷等为原料合成含2-取代-1,3-二硫杂环戊烷大环席夫碱化合物,并进行初步抑菌活性研究。结果 合成得到的中间体(Ⅰa~Ⅰc)及目标席夫碱大环化合物(Ⅱa~Ⅱc)经元素分析、红外光谱、1H-NMR、MS等手段进行了结构表征。合成的席夫碱大环化合物抑菌能力优越。结论 本试验合成了含2-取代-1,3-二硫杂环戊烷大环席夫碱化合物,其具有更加优越的抑菌能力。     

氰基环氧化物分子内的环合反应

报道了氰基环氧化物分子内的环合反应及相关环戊烷衍生物的制备，这些化合物可以被用于具有抗肿瘤活性的前列腺素Ｊ２（ＰＧＪ２）和具有抗真菌，抗病毒及其他许多生物活性的（＋）－布雷菲德菌素Ａ（ＢＦＡ）的合成。     

甾类药物的构造、构型和构象

甾类药物系指甾类激素及其类似物,主要包括性激素和肾上腺皮质激素及其衍生物,它们具有较强的生理活性,是临床常用的一类药物。从甾类药物的化学结构入手,探讨甾类药物的性质、反应和活性是研究甾类药物的基本方法。因此,有必要了解和掌握甾类药物的构造、构型和构象。甾类药物的构造甾类药物的基本构造为环戊烷并多氢菲,一般C_(10)和C_(13)各有一个甲基,称为角甲基;C_(17)常有一个含氧的功能基或一个碳     

前列地尔的剂型及研究进展

前列地尔，又名前列腺素E1，是天然前列腺素（Prostaglandinum，PG）类物质中的一种。前列腺素存在于大多数哺乳动物组织内，基本结构为含有1个环戊烷及2个脂肪侧链的20碳脂肪酸。根据环戊烷上双键位置和取代基的不同可以分为几种类型，其中主要有E、F、A、B等4类。每一类有不同的亚型，具有广泛的生物学效应。     

环维黄杨星D的结构修饰及耐缺氧活性的研究

目的 以环维黄杨星D为先导化合物进行结构修饰,以寻求更好的耐缺氧活性的衍生物.方法 将能改变药物活性和水溶性的含氮杂环化合物用于环维黄杨星D的结构修饰,合成目标化合物Ⅱa～Ⅱg.结果 合成了7个未见报道的环维黄杨星D衍生物,其结构经1 HNMR、”CNMR、MS和IR表征;同时进行了小鼠耐缺氧活性的研究.结论 合成的新化合物具有一定的生物活性,其中,含吗啉基、咪唑基、哌嗪基取代的衍生物具有较好的生物活性.     

汞配合物的合成及表征

顺氯氨铂(cis-platin,CD-DP)抗肿瘤活性的发现,为金属配合物在药学方面的应用开辟了崭新的研究领域。本文仿照1,1-环丁烷二羧酸二氨合铂的合成方法展开了一系列的实验研究,合成了三个新的汞(Ⅱ)的配合物:丙二酸一氨合汞(Ⅱ)、1,1环丁烷二羧酸一氨合汞(Ⅱ)和1,1-环戊烷二羧酸一氨合汞(Ⅱ),并对其进行了表征。     

六氢铁屎米酮盐酸盐的合成

以常用试剂代替价格昂贵且需进口的色胺为原料,经多步反应合成了有生理活性的六氢铁屎米酮盐酸盐。我们认为用此法合成它的一些衍生物也是可能的。循此路线,还可得到具有九元环的模型化合物,为一些有九元环特殊结构的吲哚碱的合成提供了一条不用色胺为原料的路线。     

核糖霉素的选择性环氨基甲酸酯保护

目的发展一种新的选择性环氨基甲酸酯保护策略，用以合成具有环氨基甲酸酯结构的新型核糖霉素衍生物。方法全苄氨羰基保护的核糖霉素在氢化钠作用下环合，通过控制反应条件选择性在不同位点引入环状氨基甲酸酯保护基。将苄氧羰基催化氢化脱除可得含有环氨基甲酸酯结构的核糖霉素衍生物。结果通过反应条件的控制成功地实现了核糖霉素的选择性环氨基甲酸酯保护。脱保护得到了的核糖霉素衍生物，但并没有预期的抗菌活性。结论含有环氨基甲酸酯的核糖霉素衍生物的合成表明选择性环氨基甲酸酯保护策略是方便可行的。具有环氨基甲酸酯结构的核糖霉素衍生物可能并不具有抗菌活性。     

Synthesis of rocaglamide hydroxamates and related compounds as eukaryotic translation inhibitors: synthetic and biological studies

The rocaglates/rocaglamides are a class of natural products known to display potent anticancer activity. One such derivative, silvestrol, has shown activity comparable to taxol in certain settings. Here, we report the synthesis of various rocaglamide analogues and identification of a hydroxamate derivative (-)-9 having activity similar to silvestrol in vitro and ex vivo for inhibition of protein synthesis. We also show that (-)-9 synergizes with doxorubicin in vivo to reduce Eμ-Myc driven lymphomas.     

Potential of cyclopenta[b]benzofurans from Aglaia species in cancer chemotherapy

During the past few years, a group of cyclopenta[b]benzofurans from the plant genus Aglaia has received broad scientific attention as interesting natural product lead compounds with potential anticancer and insecticidal activities. Since the first cyclopenta[b]benzofuran derivative, rocaglamide, from Aglaia elliptifolia, was found to exhibit antileukemic activity in a murine in vivo model, the genus Aglaia has been subjected to further investigation. Over 40 cyclopenta[b]benzofurans have been tested against different human cancer cell lines, and the cumulative results provide some important clues as to how to improve their activity through modification of their chemical structures. The semisynthesis and total synthesis of the cyclopenta[b]benzofurans have been conducted. Although the ultimate molecular target(s) responsible for their antiproliferative activity has not yet been identified, studies on their cellular mechanism of action have demonstrated that some of these compounds inhibit TNF-alpha or PMA-induced NF-kappaB activity in T-lymphocytes and induce apoptosis in different human cancer cell lines. Based on the published data thus far, cyclopenta[b]benzofurans offer excellent potential as therapeutic agent candidates in cancer chemotherapy, even if much work still remains to be done for their further development.     

Changes in isoprenoid lipid synthesis by gemfibrozil and clofibric acid in rat hepatocytes

We studied whether gemfibrozil and clofibric acid alter isoprenoid lipid synthesis in rat hepatocytes. After incubation of the cells with the agent for 74 hr, [(14)C]acetate or [(3)H]mevalonate was added, and the cells were further incubated for 4 hr. Gemfibrozil and clofibric acid increased ubiquinone synthesis from [(14)C]acetate and [(3)H]mevalonate. The effect of gemfibrozil was greater than that of clofibric acid. Also, gemfibrozil decreased dolichol synthesis from [(14)C]acetate and [(3)H]mevalonate. However, clofibric acid increased dolichol synthesis from [(3)H]mevalonate. Gemfibrozil decreased cholesterol synthesis from [(14)C]acetate and [(3)H]mevalonate. Clofibric acid decreased cholesterol synthesis from [(14)C]acetate, but did not affect synthesis from [(3)H]mevalonate. These results suggest that both agents, at different rates, activate the synthetic pathway of ubiquinone, at least from mevalonate. Gemfibrozil may inhibit the synthetic pathway of dolichol, at least from mevalonate. Contrary to gemfibrozil, clofibric acid may activate the synthetic pathway of dolichol from mevalonate. Gemfibrozil may inhibit the synthetic pathway of cholesterol from mevalonate in addition to the pathway from acetate to mevalonate inhibited by both agents.     

阿托伐他汀钙的合成研究进展

目的介绍了阿托伐他汀钙的研究背景,作用机制以及合成的研究进展。方法综合国内外报道的文献,阐述阿托伐他汀钙的合成方法。结果重点列出了3条阿托伐他汀钙的合成路线,重点分析了Paal-Knorr合成法。结论 Paal-Knorr合成法中,2种重要中间体的各种合成路线为阿托伐他汀钙的高效合成提供了新的思路。     

Enantioselective synthesis of substituted oxindoles and spirooxindoles with applications in drug discovery

This review describes recent methods for the enantioselective synthesis of oxindoles and spirooxindoles, with a particular focus on scaffolds with applications in drug discovery. The synthetic challenge of the spiro-motif and the important biological activity of spirooxindoles continue to encourage the development of creative methods to access these important structures. Unique spirocycles often result from creative synthetic methods that would not typically be identified using classical synthetic disconnections. To establish the importance of asymmetric synthesis in the context of oxindole structures, recent examples are highlighted in which stereospecific binding and differential biological activity have been demonstrated based on the configuration at the 3-position. This review is organized by type of catalyst and synthetic strategy in order to compare traditional organometallic and Lewis acid methods with more recent organocatalytic methods. A section describing multicomponent and cascade reaction strategies is also included.     

5α-还原酶抑制剂爱普列特的合成研究

目的 改善5α-还原酶抑制剂爱普列特的合成方法。方法 通过引入一种溴化物关键性中间体，以3β-羟基-5-烯-孕甾-20-酮为原料，经6步反应合成了爱普列特，总产率为45％。结果 通过本路线已合成高纯度公斤级产品。结论 该法可应用于工业规模生产。     

Effect of antioxidants on the synthesis of prostaglandins, prostacyclin and thromboxane in different layers of the kidneys of old rats

The effects of L-tocopherol and synthetic antioxidants on synthesis of prostaglandins, thromboxane B2 and prostacyclin in different layers of the kidney against the background of chronic administration of polyene antibiotics (amphotericin B, levorin, nystatin) were studied in the experiments on aged rats. It was concluded that synthetic antioxidants regulate synthesis of these biologically active substances and also are able to protect the organ from the damaging effect of polyene antibiotics.     

Neolamellarin A 及其相关吡咯类海洋生物碱合成和结构改造研究进展

Lamellarins 是一类从海洋无脊椎动物中分离的具有生物活性的吡咯生物碱, Neolamellarins,Lukianols, Storniamides, Ningalins 等结构新颖的生物碱都属于该家族。Lamellarins 吡咯类生物碱合成的关键是1,3,4-三取代吡咯环的构建,主要策略有分步构建与一锅法构建吡咯环两类,从中涌现了多种极富创新性与可行性的合成方法,既从结构多样性合成的角度丰富了化合物库,同时又以生物活性为导向提高了该类化合物的生物活性。本文对其结构特点、合成、生物活性进行了综述。     

盐酸坦索罗辛的合成

目的研究盐酸坦索罗辛的合成方法。方法以4-甲氧基苯丙酮和(R)-1-苯乙胺为起始原料,先进行不对称合成制备2-[(R)-1-(4-甲氧基苯基)]丙基-N-[(R)-1-苯乙基]胺盐酸盐,再经过氯磺化、胺解、烃化、氢解和成盐合成盐酸坦索罗辛。结果该合成工艺盐酸坦索罗辛的总收率为26%。结论该合成方法步骤短,易于操作。     

Fmoc 策略固相合成磷酰化肽研究进展

蛋白质的磷酰化和去磷酰化对多种生命活动的调节起着关键的作用,磷酰化肽是研究这些生命调节过程中一类非常重要的物质。自 20 世纪 40 年代人类首次成功地合成出磷酰化肽以来,磷酰化肽的研究就引起了化学家和生物学家的广泛关注。由于Fmoc 固相合成策略在多肽的合成中被普遍应用,因此,Fmoc 固相合成策略也已经成为目前磷酰化肽最主要的合成手段。该文对近年来采用 Fmoc 固相合成策略进行磷酰化肽合成的方法（包括整体磷酰化法和磷酰化单体合成法）进行了总结,并对各种合成方法的优缺点进行了讨论。