Catalytic Stereoselective Olefin Metathesis Reactions

催化立体选择性烯烃复分解反应

• 批准号: 8443390
• 负责人: AMIR H HOVEYDA
• 金额: $ 51.8万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443390
• 关键词: Address; Air; Alkenes; Anabolism; Anti-Bacterial Agents; Antimitotic Agents; Antineoplastic Agents; Antiviral Agents; Biological Factors; Biology; Chemistry; Complex; Development; Epothilone B; Epoxy Compounds; Ethers; Funding; Gibberellins; Healthcare; Human; Hydrogenation; Investigation; Isomerism; Kinetics; Medicine; Methods; Molybdenum; Preparation; Procedures; Process; Protocols documentation; Reaction; Research; Route; Silanes; Solutions; Staging; Stereoisomer; Tungsten; United States National Institutes of Health; antimicrobial; base; catalyst; cost effective; cycloaddition; cytotoxic; design; diene; enol; epothilone D; inhibitor/antagonist; nakadomarin A; oxidation; pressure; programs; silane

DESCRIPTION (provided by applicant): Alkenes are found in a great number of biologically active molecules and are employed in some of the most widely used transformations used to access them (such as hydrogenations, epoxidations, hydroborations, dihydroxylations, cyclopropanations, allylic substitutions, hydroformylations and cycloadditions). Many olefins exist as E or higher energy Z isomers. Processes that allow access to each isomeric form efficiently, reliably, with high selectivity and in a cost-effective fashion are therefore of substantial significance to chemistry, biology and medicine. Especially valuable are catalytic procedures for stereoselective formation of alkenes; however, such methods are uncommon. Particularly scarce are catalytic protocols that deliver Z alkenes. Research in this program is focused on the design, synthesis and development of a range of molybdenum- and tungsten-based catalysts that can be used for one of the most powerful and efficient methods for olefin synthesis: catalytic olefin metathesis. A variety of concepts, originally conceived in this NIH-funded program, will be used to introduce catalysts that can be manipulated in air and yet offer exceptional reactivity and selectivity when placed in solution in the presence of a substrate. Such catalysts will allow chemists to obtain reactivity and/or selectivity levels that remain entirely out of reach. Olefin metathesis catalysts will be developed that promote Z-selective cross-metathesis reactions of allylic ethers, epoxides, boronates, silanes as well as vinylbornates, dienes and 1,2-unsaturated carbonyls. Catalysts will be introduced that will allow chemists to prepare Z di- or trisubstituted macrocyclic alkenes, without having to forfeit nearly half of their valuable materials as the undesired stereoisomer at the late stages of a multi-step total synthesis. The new catalysts and methods will generate entities commonly viewed as the "bread and butter" of synthetic chemists, and yet their preparation often requires long and impractical routes. The special utility of the concepts, strategies, catalysts and protocols that will emerge from the proposed investigations will be highlighted through efficient approaches to syntheses of biologically significant molecules such as antimutagenic falcarindiol, antiviral chlorosufolipids, cytotoxic disorazole C1, gibberellin biosynthesis inhibitor cladospolide B, antibacterial and anticancer nakadomarin A, and anticancer agents epothilone B and neopeltolide.

描述（由申请人提供）：烷烃在大量生物活性分子中发现，并用于用于访问它们的一些最广泛使用的转换中（例如氢化，环氧化，液压，二羟基化，二羟基化，环甲基，环形抗体，烯醇化取代，水含量，水含量，cyclations和cyclations和cyclations和cyctitions）。许多烯烃作为E或更高的能量Z异构体存在。因此，允许具有高选择性和具有成本效益的方式有效，可靠地访问每个异构体形式的过程对化学，生物学和医学具有重要意义。特别有价值的是烷烃立体选择形成的催化程序；但是，这种方法并不常见。特别稀缺的是传递Z烷烃的催化方案。该程序中的研究集中在一系列基于钼和钨的催化剂的设计，合成和开发上，这些催化剂可用于烯烃合成的最强大，最有效的方法之一：催化烯烃的元素。最初在该NIH资助的程序中构思的各种概念将用于引入可以在空气中操纵的催化剂，但在底物存在下将解决方案放置在溶液中时，这些概念将具有出色的反应性和选择性。这样的催化剂将使化学家获得完全无法触及的反应性和/或选择性水平。将开发烯烃的分解催化剂，以促进Z-选择性的跨乳乙酯，环氧化物，硼酸盐，硅烷以及乙烯基寄生酸盐，二烯和1,2个不饱和的羰基的Z-选择性横断反应反应。将引入催化剂，该催化剂将使化学家能够制备Z Di-di-dibsttesttesttest的大环烷烃，而不必在多步总合成的晚期中没收其近一半的有价值材料作为不希望的立体异构体。新的催化剂和方法将产生通常被视为合成化学家的“面包和黄油”的实体，但是它们的准备工作通常需要长而不切实际的路线。概念，策略，催化剂和协议的特殊实用性将通过有效的生物学上重要分子合成的方法（例如抗寄生虫恶性含量，抗病毒氯苏脂蛋白），细胞毒素毒性毒素c1，gibberellelazole c1，gibberellellellellintherin c1，通过有效的方法来强调拟议的研究。抗菌和抗癌纳卡多蛋白A，以及抗癌剂Epothilone B和Neopeltolide。