The Total Synthesis of Bioactive Molecules and the Development of the Methodological Underpinning

生物活性分子的全合成及其方法基础的发展

• 批准号: 155431-2012
• 负责人: Kerr, Michael
• 金额: $ 7.36万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569464
• 关键词: Total; Synthesis; Bioactive; Molecules; Development

This proposal describes the development of new and useful chemical transformations and the application of those transformations to the challenge of preparing, by chemical synthesis, target molecules of biological or medicinal significance. Our research group has the long term goals of: 1) Uncovering previously unknown reactivity of existing functional groups with the aim of developing new, useful synthetic methods, 2) developing the chemistry of donor-acceptor cyclopropanes, 3) exploring new Conia-ene chemistry, 4) developing new ways to prepare and functionalize heterocyclic motifs, and 5) applying the synthetic methods above to the expedient synthesis of natural and unnatural target molecules possessing important biological activity. In this proposal we will describe our plans to address the above long term objectives as well as describing, in detail, our plans to address the following more focused shorter term objectives: 1) The development of new reactions of donor acceptor cyclopropanes including the reactions with azirines, aziridines, and diazines, 2) the exploration of unconventional dipoles such as keteneamines in useful synthetic reactions, 3) the investigation of a very recently developed pyrrole synthesis, 4) the development of a tandem Conia-ene/Diels-Alder reaction and its application in synthesis, 5) the application our Diels-Alder/ Plieninger indolization strategy to the synthesis of the natural product and 6) we will apply the methods above to the synthesis of heterocylic natural products such as tronocarpine, callosine, halichlorine and actinophyllic acid The above chemistry is anticipated to add significantly to the arsenal of chemical methodology available to the synthetic chemist. These enabling technologies will allow the synthetic chemist greater access to complex molecules by chemical synthesis. The research described in our proposal will aid in the training of chemists skilled in the synthesis of complex molecules. This will prepare them for both academic and industrial careers, particularly as pharmaceutical chemists.

该提案描述了新的和有用的化学转化的发展以及这些转化在通过化学合成制备具有生物学或医学意义的靶分子的挑战中的应用。 我们的研究团队有以下长期目标：1）发现现有官能团的先前未知的反应性，目的是开发新的有用的合成方法，2）开发供体-受体环丙烷的化学，3）探索新的Conia-烯化学，4）开发制备和官能化杂环基序的新方法，以及5）将上述合成方法应用于具有重要生物活性的天然和非天然靶分子的便利合成。 在本提案中，我们将描述我们实现上述长期目标的计划，并详细描述我们实现以下更集中的短期目标的计划：1）给体受体环丙烷的新反应的开发，包括与氮杂环丙烷、氮杂环丙烷和二嗪的反应，2）在有用的合成反应中探索非常规偶极如烯酮胺，3）最近发展的吡咯合成的研究，4）串联Conia-烯/Diels-Alder反应的发展及其在合成中的应用，5）我们的Diels-Alder/ Plieninger吲哚化策略在天然产物合成中的应用，6）我们将把上述方法应用于杂环天然产物的合成，例如：盐氯和放线菌酸 预计上述化学方法将大大增加合成化学家可用的化学方法库。 这些使能技术将使合成化学家能够通过化学合成更好地获得复杂分子。 在我们的建议中描述的研究将有助于培养熟练的化学家在复杂分子的合成。 这将为他们的学术和工业生涯做好准备，特别是作为药物化学家。