SYNTHESIS OF BIOLOGICALLY ACTIVE ALKALOIDS

生物活性生物碱的合成

基本信息

批准号：
2832112
负责人：
DAVID J HART
金额：
$ 4.08万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1980
资助国家：
美国
起止时间：
1980-04-01 至 1999-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2832112
关键词：
acylation alkaloids alkenes alkylation amines antineoplastics chemical elimination cyclization drug design /synthesis /production epoxides indoles isoquinolines ketones lactams oxidation reduction reaction racemization stereochemistry stereoisomer

项目摘要

One long-range objective of this research program is the synthesis of biologically and structurally interesting alkaloids. A second objective is the development and evaluation of methodology for the synthesis of nitrogen-containing compounds. A third objective is the discovery of biological activities associated with new nitrogen-containing organic compounds. One specific goal of this project is to continue and complete syntheses of manzamine A (1) and ircinal A (2), alkaloids of marine origin reported to have potent antitumor activity. This is to be accomplished using either macrolactamization or olefin metathesis chemistry. As part of this project, a new route to perhydroisoquinolines will be examined, with the goal being the development of a convergent route to synthetic intermediates already in hand. Selected compounds prepared during this venture are to be submitted for evaluation in biological screens related to cancer, viral, cardiovascular, gastrointestinal and CNS disorders. Another specific goal of this project is to initiate and complete a synthesis of gelsedine (3), a major alkaloid component of the plant gelsemium elegans. The route is designed to examine the scope of oxindole chemistry developed during the course of a completed synthesis of gelsemine. Selected synthetic intermediates will again be submitted for evaluation in the aforementioned biological screens.

该研究计划的一个远程目标是合成生物学和结构上有趣的生物碱。第二个目标是合成方法的发展和评估含氮化合物。第三个目标是发现与新的含氮有机物相关的生物活性化合物。该项目的一个具体目标是继续并完整合成 Manzamine A（1）和Ircinal A（2），据报道的海洋生物碱具有有效的抗肿瘤活性。这是要使用任何一个大乳酸化或烯烃化学化学。作为其中的一部分项目，将检查一条新的通往perhydroisoquinolines的途径目标是开发合成的融合路线中间已经在手里。在此期间准备的选定化合物合资企业应在与生物筛查相关的生物筛选中进行评估患癌症，病毒，心血管，胃肠道和中枢神经系统疾病。该项目的另一个具体目标是启动并完成凝胶氨酸的合成（3），植物的主要生物碱成分凝胶秀丽隐杆线。该路线旨在检查氧吲哚的范围化学在完整的合成过程中开发凝胶。选定的合成中间体将再次提交在上述生物筛选中进行评估。