Scalable Synthesis and New Bond Disconnections

可扩展的合成和新的键断裂

基本信息

批准号：
10580740
负责人：
PHIL S BARAN
金额：
$ 111.58万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10580740
关键词：
Acceleration Address Adoption Alkaloids Architecture Biochemical Pathway Biological Biomedical Research Breathing Chemicals Collaborations Complex Development Drug Industry Environment FDA approved Family Folk Medicine Human body Industrialization Knowledge Laboratories Literature Mediator Methodology Methods Modernization Natural Products Nature Organic Chemistry Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Procedures Property Reagent Research Scientist Source Synthesis Chemistry Terpenes Transcend commercialization cost drug discovery field study interest invention novel programs scaffold success

Acceleration Address Adoption Alkaloids Architecture Biochemical Pathway Biological Biomedical Research Breathing Chemicals Collaborations Complex Development Drug Industry Environment FDA approved Family Folk Medicine Human body Industrialization Knowledge Laboratories Literature Mediator Methodology Methods Modernization Natural Products Nature Organic Chemistry Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacologic Substance Procedures Property Reagent Research Scientist Source Synthesis Chemistry Terpenes Transcend commercialization cost drug discovery field study interest invention novel programs scaffold success

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项目摘要

PROJECT SUMMARY/ABSTRACT Natural products have long held societal value as folk medicines, and even in this modern era, many FDA-approved drugs are still being derived from terpenes and alkaloids found in nature. Biomedical research has also benefited from natural products, as previously unknown mechanisms of action have been discovered while studying the unique biochemical pathways that these compounds undergo in the human body. Furthermore, endeavors in the total synthesis of these architecturally diverse compounds have continuously provided chemists with challenges, which in turn have led to the establishment of research programs in both academic and industrial environments. Ever since its inception, our laboratory has been pursuing, and has succeeded in, the total synthesis of iconic natural products in both the terpene and alkaloid families. These syntheses have identified gaps in the chemical literature, which we have subsequently addressed. The products of this research program—new synthetic strategies, unprecedented transformations and novel reagents—have in turn enabled the synthesis of even more natural products and pharmaceutically relevant motifs, thus completing a catalytic cycle of discovery. We seek to replicate this success with the current proposal: the described projects will target complex natural products to identify shortcomings in chemical methodology, while simultaneously devising methods of widespread interest, followed by the assessment of their practicality in the synthesis of complex molecules. For the next five years our laboratory will generate chemical knowledge that transcends the original objective of natural product synthesis. We will focus on efficiently synthesize complex natural products aiming for ideality. We will also develop of useful methods for synthesis and medicinal chemistry. The resulting procedures will be utilized in the construction of complex pharmaceutical motifs, which will serve to expand chemical space and accelerate discovery in drug discovery. Notably, we have already established numerous collaborations to study the biological properties of the products that will be synthesized, to validate and field-test new methods, and to commercialize reagents for widespread adoption in both academic and industrial settings. Lastly, we will focus on strategic applications and development of synthetic organic electrochemical methods, wherein the development of oxidative mediators for C-H functionalization, desaturation of carbonyls, and reductive cross-couplings are presented.

项目摘要/摘要天然产品长期以来一直具有民间药物的社会价值，甚至在现代时代，许多由FDA批准的药物仍来自自然界中发现的萜烯和生物碱。生物医学研究也从天然产品中受益，如以前未知的在研究独特的生化途径时已经发现了作用机制这些化合物在人体中经历。此外，总合成的努力这些建筑上多样的化合物继续为化学家提供挑战，这反过来导致在学术和工业中建立了研究计划环境。自成立以来，我们的实验室一直在追求并成功，萜烯和生物碱家族中标志性天然产物的总合成。合成已经确定了我们随后解决的化学文献中的差距。该研究计划的产品 - 新合成策略，前所未有的转换和新颖的试剂 - 反过来又可以合成更多天然产品和药物相关的基序，从而完成了发现的催化循环。我们寻求通过当前的建议复制这一成功：所述项目将针对复杂的自然识别化学方法的缺点的产品，同时设计宽度兴趣的方法，然后在合成中评估其实践复杂分子。在接下来的五年中，我们的实验室将产生化学知识这超越了天然产物合成的原始目标。我们将有效地专注于合成旨在理想的复杂天然产品。我们还将开发有用的方法用于合成和医学化学。最终的程序将用于施工复杂的药物图案，该图案将用于扩大化学空间并加速在药物发现中发现。值得注意的是，我们已经建立了许多合作研究将合成的产品的生物学特性，以验证和现场测试新方法，并在学术和工业环境。最后，我们将专注于战略应用和合成的发展有机电化学方法，其中C-H的氧化介质的发展提出了功能化，羰基的去饱和度和交叉耦合减少。