Scalable Synthesis and New Bond Disconnections
Scalable Synthesis and New Bond Disconnections
批准号:
9677411
负责人:
PHIL S BARAN
金额:
$9.62万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-04-01 至 2021-03-31
关键词:
AddressAdoptionAlkaloidsAlkenesArchitectureBiochemical PathwayBiologicalBiomedical ResearchBreathingCarbonChemicalsChemistryCollaborationsComplexDevelopmentDimerizationDrug IndustryElectrochemistryEnvironmentFDA approvedFamilyFluorineFolk MedicineGoalsHuman bodyHydrogen BondingIndustrializationKnowledgeLaboratoriesLiteratureMethodologyMethodsModernizationNatural ProductsNatureOrganic ChemistryPharmaceutical ChemistryPharmaceutical PreparationsPharmacologic SubstanceProceduresPropertyReagentResearchScientistSourceTerpenesTranscendcostfield studyinterestnoveloxidationprogramsscaffoldsuccess
中文摘要
菲尔·巴兰
项目概要/摘要
天然产品作为民间药物长期以来一直具有社会价值,即使在这个现代时代,
FDA批准的药物仍然来自自然界中发现的萜烯和生物碱。生物医学
研究也受益于天然产品,因为以前未知的作用机制已经被发现。
在研究这些化合物在人体内的独特生化途径时发现的
身体此外,在这些结构上不同的化合物的全合成方面的努力已经取得了进展。
不断为化学家提供挑战,这反过来又导致了研究的建立
在学术和工业环境中的计划。自成立以来,我们的实验室一直
追求,并已成功地,在萜烯和
生物碱家族这些合成已经确定了化学文献中的空白,
随后处理。这项研究计划的产物-新的合成策略,前所未有的
转化和新试剂-反过来又使得能够合成更多的天然产物,
药物相关的基序,从而完成发现的催化循环。我们试图复制这种
目前提案的成功:所述项目将针对复杂的天然产品,
化学方法的缺点,同时设计出广泛关注的方法,
然后评估它们在合成复杂分子中的实用性。
该提案分为三个部分,其总体目标是产生化学品,
超越天然产物合成的原始目标的知识。第一部分描述了
后期氧化高效合成复杂萜类和生物碱类天然产物的方案。的
该提案的第二部分认为,电化学可以是一种实用、廉价、无毒,
一个可扩展的解决方案,以各种化学问题,其中N-H键的二聚天然产物
合成,用于药物开发的杂芳烃取代,以及用于
功能化的term类型的框架。最后,第三部分说明了通用的
烯烃衍生的碳中心自由基形成C-C和C-N键的反应性
不切实际的或不可能创造的。由此产生的程序将用于建设复杂的
和空间阻碍的药物基序,这将有助于扩大化学空间,
加速药物化学的发现值得注意的是,我们已经建立了许多合作关系,
研究将要合成的产品的生物特性,验证和实地测试新的
方法,并将试剂商业化以在学术和工业环境中广泛采用。
英文摘要
BARAN, PHIL S.
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 establishement 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.
This proposal is organized into three parts with the overarching goal of generating chemical
knowledge that transcends the original objective of natural product synthesis. The first section delineates
plans for late-stage oxidation to efficiently synthesize complex terpene and alkaloid natural products. The
second portion of the proposal argues that electrochemistry can be a practical, inexpensive, non-toxic, and
scalable solution to a variety of chemistry problems, wherein dimerization of N–H bonds for natural product
synthesis, heteroarene fluorination for pharmaceutical development, and allylic oxidation for the
functionalization of terpene-type frameworks are presented. Lastly, the third section illustrates the versatile
reactivity of olefin-derived, carbon-centered radicals to forge C–C and C–N bonds that are otherwise
impractical or impossible to create. The resulting procedures will be utilized in the construction of complex
and sterically encumbered pharmaceutical motifs, which will serve to expand chemical space and
accelerate discovery in medicinal chemistry. 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.
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会议论文
Scalable Synthesis and New Bond Disconnections
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批准号:10373114
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Scalable Synthesis and New Bond Disconnections
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批准号:8996063
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资助金额:$51.73万
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批准号:8485337
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资助金额:$51.73万
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财政年份:2013
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负责人:PHIL S BARAN
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依托单位:
Synthesis of Complex Terpenes
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批准号:8636031
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项目类别:
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资助金额:$36.01万
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财政年份:2011
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负责人:PHIL S BARAN
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依托单位:
Synthesis of Complex Terpenes
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批准号:8242687
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项目类别:
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资助金额:$36.01万
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财政年份:2011
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负责人:PHIL S BARAN
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依托单位:
Synthesis of Complex Terpenes
-
批准号:8080703
-
项目类别:
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资助金额:$36.01万
-
财政年份:2011
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负责人:PHIL S BARAN
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依托单位:
Synthesis of Complex Terpenes
-
批准号:8446414
-
项目类别:
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资助金额:$34.74万
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财政年份:2011
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负责人:PHIL S BARAN
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依托单位:
Total Synthesis of Anti-Cancer Natural Products
-
批准号:7674771
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资助金额:$63.05万
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财政年份:2009
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依托单位:
Oxidative Coupling in Natural Product Synthesis
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资助金额:$35.42万
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Oxidative Coupling in Natural Product Synthesis
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批准号:7105690
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资助金额:$35.79万
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财政年份:2006
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依托单位:
Oxidative Coupling in Natural Product Synthesis
-
批准号:7225605
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资助金额:$34.75万
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财政年份:2006
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依托单位:
Oxidative Coupling in Natural Product Synthesis
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Synthesis of Pyrrole-Imidazole Alkaloids
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资助金额:$28.22万
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财政年份:2005
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负责人:PHIL S BARAN
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依托单位:
Synthesis of Pyrrole-Imidazole Alkaloids
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依托单位:
海外基金