CHARACTERIZATION OF HEART ATRIAL MUSCARINIC RECEPTOR

一种快速分离新的同系物的新方法 线状四氢呋喃类细胞毒激素罗力宁和罗力农 从斜纹卷蛾(Rollinia Parilionella)、丝状卷蛾(R.sericea)和微小卷叶卷蛾(R.microsepala) 调查过了。其中几种乙酰生素已显示出体内活性。 抗小鼠P388淋巴细胞性白血病。其他同源物将 使用Sephadex柱层析分离，并将表征 使用核磁共振和质谱学方法。由于……的作用机制 这些抗肿瘤化合物是未知的，一项结构-活性研究 将启动以确定需要哪些功能组来 显示出细胞毒活性。乙酸根素，特别是 双四氢呋喃部分，对各种反应都很敏感 条件。因此，将合成模型化合物并将其用于 开发用于改性活性物质的反应条件 原则。模型化合物的双四氢呋喃部分将是 通过适当的三环氧化合物的拉链反应合成。这个 三环氧化物将由相应的三烯制备，该三烯将是 通过一系列的Wittig反应构建。 美坦辛临床样品的分解产物为 经核磁共振和质谱学方法分离鉴定。这个 识别这些分解产物可能会提供一些洞察力 美坦辛作为抗肿瘤药物时的新陈代谢 毒品。次要的美丹素类化合物将从美天奴M。 Senegalens和M.putterlickoids.这些梅坦辛诺类化合物将是 通过与已知的梅坦素类化合物的比较以及通过核磁共振和质谱学鉴定 光谱数据。新的美坦素类化合物将进行细胞毒性筛选，并可能 以美丹参酚为原料，经半合成，大批量制备 活体测试。经修饰的美赞臣类化合物也将从 用于进一步评价结构-活性关系的美坦辛醇 在这一系列有效的抗肿瘤药物中。侧边的修改 将制备链酯和醚衍生物。 活性导向分级法分离白花蛇舌草提取物的研究 满天星也将启动。

A new procedure for the rapid isolation of additional homologues of the cytotoxic linear bistetrahydrofuranoid acetogenins rollinicin and rollinone from Rollinia papilionella, R. sericea, and R. microsepala will be investigated. Several of these acetogenins have shown in vivo activity against the P388 lymphocytic leukemia in mice. Additional homologues will be isolated with the use of a Sephadex column and will be characterized using NMR and mass spectral methods. Since the mechanism of action of these antineoplastic compounds is not known, a structure-activity study will be initiated to determine which functional groups are required to demonstrate cytotoxic activity. The acetogenins, particularly the bistetrahydrofuran moiety, are sensitive to a variety of reaction conditions. Therefore, model compounds will be synthesized and used to develop the reaction conditions to be used to modify the active principles. The bistetrahydrofuran portion of the model compounds will be synthesized via a 'zipper' reaction of an appropriate triepoxide. The triepoxide will be prepared from the corresponding triene which will be constructed via a series of Wittig reactions. The decomposition products of clinical samples of maytansine will be isolated and identified by NMR and mass spectral methods. the identification of these decomposition products may provide some insight into the metabolism of maytansine when administered as an antineoplastic drug. Minor maytansinoids will be isolated from Maytenus rothiana, M. senegalensis, and M. putterlickoides. These maytansinoids will be identified by comparisons to known maytansinoids and by NMR and mass spectral data. New maytansinoids will be screened for cytotoxicity and may be prepared in larger quantities by semi-synthesis from maytansinol for in vivo testing. Modified maytansinoids will also be prepared from maytansinol for further evaluation of the structure-activity relationships in this series of potent antineoplastic agents. Modifications of the side chain ester and ether derivatives will be prepared. Activity-guided fractionation of extracts of Schrebera alata and Gypsophilia paniculata will also be initiated.