NOVEL ASYMMETRIC SYNTHESIS OF ANTI-AIDS COMPOUNDS

抗艾滋病化合物的新型不对称合成

• 批准号: 3304404
• 负责人: Joseph Paul Konopelski
• 金额: $ 13.04万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-06-05 至 1994-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3304404
• 关键词: alpha glucosidase; antiAIDS agent; antibiotics; antiviral agents; castanospermine; chemical reaction; chemical structure function; drug design /synthesis /production; enzyme inhibitors; human immunodeficiency virus; nucleic acid chemical synthesis; oxetane; reverse transcriptase inhibitors; stereochemistry

The principle objectives of the research program as set forth in this proposal are the development and execution of efficient asymmetric syntheses of the structural types found in the natural products castanospermine, deoxynojirimycin, and other glucosidase inhibitors, and oxetanocin, a novel oxetane-containing nucleosides with reverse transcriptase inhibitory activity. Members of these structurally distinct classes of compounds are being intensely scrutinized because of their anti- human immunodeficiency virus (HIV) activity. While we illustrate our strategy with syntheses of the natural compounds, our primary concern is with the definition of synthetic routes that are general enough so that the synthesis of analogs can be pursued directly, without the need to redesign the synthetic protocol for each new derivative. Thus, we expect that the generality of our synthetic approaches will allow for the facile production of new molecules structurally related to the target compounds (i.e., analogs), thereby enabling a better understanding of the relationship of chemical architecture and biological function. Certain analog syntheses are discussed in this proposal.

研究计划的主要目标，如本 建议是制定和执行有效的不对称 天然产物中发现的结构类型的合成 栗精胺、脱氧野尻霉素和其他葡糖苷酶抑制剂，以及 oxetanocin，一种新的含氧杂环丁烷的核苷， 转录酶抑制活性。 这些结构不同的成员 化合物的类别正在受到严格的审查，因为它们的反- 人类免疫缺陷病毒（HIV）活性。 当我们用天然化合物的合成来说明我们的策略时， 我们主要关心的是合成路线的定义， 足够普遍以致可以直接进行类似物的合成， 而不需要为每个新的合成方案重新设计合成方案， 衍生物 因此，我们希望我们的合成的一般性， 这种方法将允许新分子的简单生产， 结构上与目标化合物相关（即，类似物），从而 更好地理解化学物质之间的关系 结构和生物功能。 某些类似物合成是 在这个提案中讨论。