Synthesis and Study of Medicinally Important Molecules

项目总结/摘要 我们研究计划的目标是创新有机合成和使用的策略和方法 这些创新解决了生物学和医学上的重要问题，并最终影响了人类 健康我们的计划侧重于天然和非天然分子的合成和研究， 用于治疗癌症、神经系统疾病和耐药性传染病。我们认为 完成化学合成作为更大和更深入的学术研究的开始。它将使 我们可以分析所选天然产物和合理设计的小分子的生物学特征， 作用机制，并优化先导化合物成为生物探针和新的治疗药物。的 选择的萜类化合物和生物碱天然产物代表了复杂化合物的最新挑战， 分子合成以及有前景的先导化合物用于新的治疗开发。它们的结构 复杂性、自然稀缺性和未知的作用机制极大地阻碍了它们的生物医学 发展我们的目标是填补这一空白，并推动这些分子在药物发现管道中向前发展， 以创新的化学合成为中心的多方面方法。本研究的预期结果 将提供（i）药物化学家和合成化学家工具箱中的新反应和策略， 制备功能分子，（ii）可靠地获得所选靶分子， 重要性，（iii）具有结构新奇、复杂性和 在学术机构和制药行业进行进一步和更大规模的生物学评价的多样性， 和（iv）新的抗癌、抗神经变性和抗微生物先导化合物，其具有潜在的新的 用于体内和临床评价的作用模式。

Project Summary/Abstract The goal of our research program is to innovate the strategy and methodology of organic synthesis and use these innovations to solve problems of biological and medicinal importance and ultimately impact human health. Our program focuses on the synthesis and study of both natural and unnatural molecules with potential for the treatment of cancer, neurological disorders, and drug resistant infectious diseases. We view the completion of a chemical synthesis as the beginning of a larger and deeper scholarly inquiry. It would enable us to profile the biology of the selected natural products and rationally designed small molecules, decipher their mechanism of actions, and optimize the lead compounds into biological probes and novel therapeutics. The selected terpenoid and alkaloid natural products represent both the state-of-the-art challenges for complex molecule synthesis as well as promising lead compounds for novel therapeutic development. Their structural complexity, natural scarcity, and unknown mechanism of actions have significantly hampered their biomedical development. We aim to fill this gap and move these molecules forward in the drug discovery pipeline with a multi-faceted approach centered on innovative chemical synthesis. The expected outcomes of this research will provide (i) new reactions and strategies in the toolbox of both medicinal chemists and synthetic chemists to prepare functional molecules, (ii) a reliable access to the selected target molecules with therapeutic importance, (iii) a collection of medicinally relevant molecules featuring structural novelty, complexity, and diversity for further and larger biological evaluations in academic institutions and pharmaceutical industries, and (iv) novel anticancer, anti-neurodegenerative and antimicrobial lead compounds with potentially novel mode of actions for in vivo and clinical evaluations.