SYNTHETIC REACTIONS CATALYZED BY TRANSITION METALS

过渡金属催化的合成反应

基本信息

批准号：
7325763
负责人：
EI-ICHI NEGISHI
金额：
$ 34.6万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1986
资助国家：
美国
起止时间：
1986-07-01 至 2010-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7325763
关键词：
Academia Adopted Affect Aldehydes Alkenes Alkynes Amphotericin B Area Attention Biological Biological Factors Carbon Carotenoids Complement Complex Coupling Development Evaluation Funding Goals Grant Hydrogenation Investigation Marketing Metals Methodology Methods Modification Natural Product Drug Numbers Object Attachment Organic Synthesis Pharmaceutical Preparations Positioning Attribute Preclinical Drug Evaluation Preparation Procedures Production Property Protocols documentation Purpose Reaction Research Research Project Grants Screening procedure Support of Research Transition Elements United States National Institutes of Health apoptolidin callystatin A calyculin A catalyst comparative delactonmycin desire discodermolide hennoxazole A improved innovation interest literature survey milbemycin milbemycins mycolactone A nafuredin novel protocol development ratjadone two-dimensional zincophorin

项目摘要

The long-term goal of the ongoing and proposed research project is to fundamentally innovate organic synthesis such that a wide variety of organic compounds of biological and medicinal significance can be prepared in efficient, selective, practically useful, and economical manners. Critically needed is to keep improving substantially and continuously organic synthesis through introduction of new and superior synthetically useful reactions, protocols, and procedures. In the NIH-supported research project, this goal has been pursued primarily through active and judicious incorporation of fundamentally superior reactions employing transition metals and their complexes primarily as catalysts, such as the Pd-catalyzed cross-coupling and the Zr-catalyzed carboalumination of alkynes. During the current grant period, the Zr-catalyzed asymmetric carboalumination of alkenes (ZACA reaction hereafter) discovered by the PI has been developed into a general and potentially useful asymmetric carbon-carbon bond-formation reaction. Thus, the use of the ZACA reaction in target-guided development of protocols and procedures for the synthesis of chiral organic compounds, especially those alkenes, oligoenes, oligoenynes that contain one or more proximal asymmetric carbon centers is one of the main specific aims of the proposed research. It is fully intended to seek unprecedentedly high levels of efficiency and selectivity such that the preparation of the desired complex molecules would become genuinely practical for various purposes including medicinal screening and even industrial production. Some of the target compounds whose total syntheses will be attempted during the proposed grant period include mycolactones A and B, delactonmycin, ratjadone, lacrimin A, fluvirucinin A, as well as some (Z)-carotenoids and oligoynes. Equally important in the proposed research are syntheses of those fragments of compounds of biological and medicinal interest that are highly pertinent to the proposed methodological investigations. Being considered for this purpose are discodermolide, hennoxazole A, zincophorin, roselipins, apoptolidin, nafuredin, caIlystatin A, milbemycin p3, calyculin A, and amphotericin B.

正在进行和拟议的研究项目的长期目标是从根本上创新有机合成，使多种生物和有机化合物可以高效、选择性、实用、经济地制备具有药用意义的药物礼仪。迫切需要的是不断实质性地、持续地有机地改进通过引入新的和优越的合成有用的反应、方案和方法进行合成程序。在 NIH 支持的研究项目中，这个目标主要是为了实现通过积极而明智地结合根本上优越的反应过渡金属及其配合物主要作为催化剂，例如 Pd 催化的交叉偶联和 Zr 催化的炔烃碳铝化反应。在本次赠款期间在此期间，Zr 催化的烯烃不对称碳铝化反应（ZACA 反应） PI 发现的以下内容已发展为通用且可能有用的不对称碳-碳键形成反应。因此，ZACA 反应的使用目标引导的手性合成方案和程序的开发有机化合物，尤其是那些含有一种物质的烯烃、寡烯、寡烯炔或更近的不对称碳中心是该研究的主要具体目标之一提出的研究。它完全是为了寻求前所未有的高水平效率和选择性使得所需复杂分子的制备真正变得适用于各种目的，包括药物筛选甚至工业生产。部分拟进行全合成的目标化合物拟议的资助期包括 mycolactones A 和 B、delactonmycin、ratjadone、lacrimin A、 Fluvirucinin A，以及一些 (Z)-类胡萝卜素和寡炔。同样重要的是在拟议的研究是生物和药物化合物片段的合成与拟议的方法学研究高度相关的兴趣。存在为此目的考虑的药物有discodermolide、hennoxillaxole A、zinophorin、roselipins、凋亡素、nafuredin、calystatin A、米尔倍霉素 p3、calyculin A 和两性霉素 B。