SYNTHETIC REACTIONS CATALYZED BY TRANSITION METALS

过渡金属催化的合成反应

基本信息

批准号：
7212329
负责人：
EI-ICHI NEGISHI
金额：
$ 36.82万
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/7212329
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

DESCRIPTION (provided by applicant): 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 1 or more proximal asymmetric carbon centers is 1 of the main specific aims of the proposed research. It is fully intended to seek unprecedented 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 B3, calyculin A, and amphotericin B.

描述（由申请人提供）：正在进行和拟定的研究项目的长期目标是从根本上创新有机合成，以便可以高效、选择性、实用和有效地制备各种具有生物和医学意义的有机化合物。经济的举止。迫切需要的是通过引入新的、更优越的合成有用的反应、方案和程序来持续实质性地改进有机合成。在美国国立卫生研究院支持的研究项目中，这一目标主要是通过积极而明智地结合使用过渡金属及其络合物作为催化剂的根本上优越的反应来实现的，例如钯催化的交叉偶联和锆催化的炔烃碳铝化反应。在当前的资助期内，PI发现的Zr催化的烯烃不对称碳铝化反应（以下简称ZACA反应）已发展成为一种通用且具有潜在用途的不对称碳碳键形成反应。因此，在手性有机化合物合成的方案和程序的目标引导开发中使用ZACA反应，特别是那些含有1个或多个近端不对称碳中心的烯烃、寡烯、寡烯炔是该项目的主要具体目标之一。提出的研究。其完全旨在寻求前所未有的高水平效率和选择性，以便所需复杂分子的制备真正可用于各种目的，包括药物筛选甚至工业生产。在拟议的资助期内将尝试全合成的一些目标化合物包括 mycolactones A 和 B、delactonmycin、ratjadone、lacrimin A、fluvirucinin A 以及一些 (Z)-类胡萝卜素和寡炔。在拟议的研究中同样重要的是与拟议的方法学研究高度相关的具有生物和医学意义的化合物片段的合成。用于此目的的考虑有discodermolide、hennoxazo A、zincophorin、roselipins、apoptolidin、nafuredin、calystatin A、milbemycin B3、calyculin A 和两性霉素 B。