CHARACTERIZATION OF HEART ATRIAL MUSCARINIC RECEPTOR

一种新的快速分离其他同系物的方法， 细胞毒性线性双四氢呋喃类乙酸配基罗力菌素和罗力酮 （Rollinia papilionella，R.）sericea，和R.小萼片将是 研究了 这些乙酸配基中的几种已显示出体内活性 对小鼠P388淋巴细胞白血病的抑制作用。 其他同系物将 使用Sephadex柱分离，并进行表征 使用核磁共振和质谱方法。 由于其作用机制 这些化合物是未知的，结构活性研究 将启动以确定需要哪些功能组 显示细胞毒活性。 乙酸配基，特别是 双四氢呋喃部分，对各种反应敏感 条件 因此，将合成模型化合物并用于 开发用于改性活性的反应条件， 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物的“拉链”反应合成。 的 三环氧化物将由相应的三烯制备， 通过一系列的维蒂希反应。 美登素临床样品的分解产物将是 通过NMR和质谱方法分离和鉴定。 的 对这些分解产物的鉴定可以提供一些见解 进入美登素的新陈代谢， 药 少量的美登木素生物碱将从美登木中分离得到。 senegalensis和M. putterlickoides。 这些美登素类化合物 通过与已知的美登木素生物碱的比较以及通过NMR和质谱鉴定 光谱数据 将筛选新的美登木素生物碱的细胞毒性， 通过从美登醇半合成以更大的量制备， 体内试验 改性的美登木素生物碱也将由以下制备： 美登醇，用于进一步评价构效关系 在这一系列的强效杀菌剂中。 侧面的修改 将制备链酯和醚衍生物。 阿拉塔提取物的活性导向分级 还将启动Gypsophilia paniculata。

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.