SYNTHESIS OF BIOLOGICALLY SIGNIFICANT INDOLES

我们建议将吲哚部分引入4-氧代-3- 喹啉羧酸，一类新型高效抗菌剂。 在所有可能的环位置上都有胺基取代的吲哚将 合成并用作潜在抗生素的前体。 这些氨基吲哚与β-二羰基加合物的缩合将 提供可环化成最终的4-喹诺酮结构的丙烯酰胺。 抗菌素敏感性测试将在以下机构的赞助下进行 子项目I。 我们还将完成选定的褪黑素的基本准备工作 前体和类似物，并提交给国家癌症研究所 测试为细胞有丝分裂抑制物。减少以前准备的 产物的吲哚乙腈和最终的乙酰化将产生 类比。我们还将继续评估这一反应的范围 含亚硫酸氢钠的吲哚类化合物对吲哚的潜在意义 和药物化学。 为了完成这项工作，我们打算让学生参与到以下各个方面 这些化合物的合成和表征将 利用至少15种不同类型的化学反应，其中一些可能 是在特定领域的首次应用。该项目确实提供了 对任何特定方面进行扩展和/或更详细检查的空间 可能证明这一点的研究的结论。

We propose to incorporate the indole moiety into 4-oxo-3- quinolinecarboxylic acids, a new class of potent antibiotic agents. Indoles having amine groups substituted in all possible ring positions will be synthesized and utilized as precursors of the potential antibiotics. Condensation of these aminoindoles with beta-dicarbonyl adducts will provide acryaltes which may be cyclized to the final 4-quinolone structure. Antimicrobial susceptibility testing will take place under the auspices of subproject I. We will also complete the basic preparation of selected melatonin precursors and analogs and submit them to the National Cancer Institute for testing as cell mitosis inhibitors. Reduction of the previously prepared indoleacetonitriles and final acetylation of the products will yield the analogs. We will also continue to evaluate the scope of the reaction of indoles with sodium bisulfite due to its potential significance to indole and medicinal chemistry. To accomplish this work, we intend to involve students in all aspects of the synthesis and characterization of these chemical compounds which will utilize at least 15 different types of chemical reactions some of which may be first-time applications in a specific area. The project does provide room for expansion and/or more detailed examination of any particular facet of the research which may prove to warrant such.