SYNTHESIS OF BIOLOGICALLY SIGNIFICANT INDOLES

具有生物学意义的吲哚的合成

• 批准号: 3856157
• 负责人: H F RUSSELL
• 金额: --
• 依托单位: JOHNSON C. SMITH UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3856157
• 关键词: acetylation; autoradiography; drug design /synthesis /production; histochemistry /cytochemistry; indoleamine; indoles; ion exchange chromatography; phosphomonoesterases; quinolinate

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.

我们建议将吲哚部分并入4-氧代-3-甲基吲哚中。 喹啉羧酸，一类新的有效抗生素。 在所有可能的环位置上具有取代的胺基的吲哚将 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 提供可环化为最终4-喹诺酮结构的丙烯酸酯。 抗菌药物敏感性测试将在以下机构的主持下进行： 次级项目一 我们还将完成选定褪黑激素的基本准备工作 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剂。 减少以前编制的 吲哚乙腈和最终的乙酰化产物将产生 类似物 我们还将继续评估 由于亚硫酸氢钠对吲哚的潜在重要性， 和药物化学。 为了完成这项工作，我们打算让学生参与各个方面的工作， 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，其中一些可以 第一次应用于特定领域。 该项目提供 任何特定方面的扩展和/或更详细检查的空间 可能证明有必要的研究。