Strategies and Methods for Complex Alkaloid Synthesis

复杂生物碱合成的策略和方法

基本信息

批准号：
7479167
负责人：
Erik J. Sorensen
金额：
$ 26.95万
依托单位：
PRINCETON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2009-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7479167
关键词：
2-aminoimidazole Alkaloids Alkenes Alkynes Amides Anions Antimitotic Agents Antineoplastic Agents Applications Grants Architecture Biological Biological Factors Carbon Cations Chemicals Chemistry Chlorine Claisen rearrangement Complex Constitution Cyclization DNA Sequence Rearrangement Denmark Development Diterpenes Electrons Elements Equilibrium Evolution Facility Construction Funding Category Foundations Goals Grant Human Imidazole Immunosuppressive Agents Indoles Investigation Kinesin Laboratories Lactams Maps Marines Mediating Memory Metals Methods Mitotic Molecular Motor Motor Activity Nature Nitrogen Numbers Object Attachment Organic Synthesis Palau Palau&apos amine Palladium Photochemistry Plant alkaloid Principal Investigator Process Property Proteins Rattus Reaction Research Research Personnel Route Scheme Sodium Staging Structure System T-Cell Proliferation Tyrosine acutumine chemical reaction chemical synthesis concept coping cytotoxic design indole inhibitor/antagonist innovation inorganic phosphate insight interest irradiation marine natural product novel oxidation programs terpendole E

项目摘要

DESCRIPTION (provided by applicant): The objective of this research program is to develop powerful strategies and reactions to transform simple, commercially available compounds into structurally complex, nitrogen-containing molecules with high efficiency and in a practical fashion. By undertaking syntheses of biologically active alkaloids having a high level of architectural and/or stereochemical complexity, our ultimate goal is to extend the capabilities of chemical synthesis through the development of innovative strategies and efficient bond-forming reactions. The methods section of the research plan is divided into 5 parts. The first part describes the evolution of our design for synthesizing acutumine, a unique, chlorine-containing plant alkaloid that enhances memory in rats and inhibits human T-cell proliferation with moderate potency. The development of a 5-step synthesis of the complex molecular framework of acutumine will provide the foundation for an eventual total synthesis of this alkaloid and related nitrogen-containing compounds. The second part describes our effort to develop a concise synthesis of terpendole E featuring a novel cation-olefin cascade cyclization process. Terpendole E, a complex indole diterpene, is the only known natural product inhibitor of the motor activity of the human mitotic kinesin Eg5 and is a potential anti-cancer agent. Parts 3 and 4 describe our plans for developing unconventional photochemical cyclizations in the context of syntheses of the scarce, architecturally remarkable marine alkaloids chartelline A and chartellamide A. The final part describes our ongoing effort to develop metal-catalyzed, cis-selective chloroaminations of alkenes for use in a total synthesis of the potent immunosuppressive and cytotoxic alkaloid palau'amine. The structurally novel, biologically active alkaloids described in this grant application are attractive objectives for chemical research because successful strategies for their synthesis do not yet exist. These molecules provide rich opportunities to invent powerful strategies and broadly useful methods for complex chemical synthesis.

描述（由申请人提供）：该研究计划的目的是开发强大的策略和反应，以高效和实用的方式将简单的，市售的化合物转化为结构复杂的含氮分子。通过实现具有高水平的建筑和/或立体化学复杂性的生物活性生物碱的合成，我们的最终目标是通过发展创新策略和有效的键形反应来扩展化学合成的能力。研究计划的方法部分分为5个部分。第一部分描述了我们设计用于合成的丙硫氨氨酸的设计，这是一种独特的，含氯的植物生物碱，可增强大鼠的记忆并抑制人类T细胞增殖，并具有适度的效力。阿申氨酸复杂分子框架的5步合成的发展将为最终的总合成这种生物碱和相关的含氮化合物提供基础。第二部分描述了我们为开发带有新型阳离子 - 烯烃级联环化过程的terpendole e的简洁合成的努力。 Terpendole E是一种复杂的吲哚二萜，是人类有丝分裂驱动蛋白EG5运动活性的唯一已知天然产物抑制剂，并且是潜在的抗癌剂。第3部分和第4部分描述了我们在稀缺的，建筑上鲜明的海洋生物碱Chartelline A和Chartellamide A的合成背景下制定非常规光化学环化的计划。最终部分描述了我们持续的努力，描述了我们持续的努力，以开发金属催化的，顺式催化的，顺式培养的，顺式促进的碱性，供碱性合成中的合成量，并构成谷物的含量。生物碱palau'amine。本赠款应用中描述的结构新颖的生物学活性生物碱是化学研究的有吸引力目标，因为尚不存在成功的合成策略。这些分子为发明强大的策略和广泛有用的化学合成方法提供了丰富的机会。