Catalytic Stereoselective Olefin Metathesis Reactions

说明书(申请人提供)：烯烃存在于大量生物活性分子中，并被用于一些最广泛使用的转化中(如氢化、环氧化、氢硼化、二羟基化、环丙烷化、烯丙基取代、氢甲酰化和环加成)。许多烯烃以E或更高能的Z异构体形式存在。因此，允许高效、可靠、高选择性和以成本效益的方式获得每一种异构体的过程对化学、生物和医学具有重要意义。特别有价值的是用于烯烃立体选择性形成的催化程序；然而，这种方法并不常见。特别稀缺的是提供Z-烯烃的催化方案。该项目的研究重点是一系列钼和钨基催化剂的设计、合成和开发，这些催化剂可用于最有效和最有效的烯烃合成方法之一：催化烯烃歧化反应。这项由美国国立卫生研究院资助的计划中最初构思的各种概念将被用来引入催化剂，这些催化剂可以在空气中操纵，但在底物存在的情况下放置在溶液中时，仍具有非凡的反应活性和选择性。这样的催化剂将允许化学家获得完全无法达到的反应活性和/或选择性水平。将开发烯烃歧化催化剂，以促进烯丙基醚、环氧化物、硼酸盐、硅烷以及乙烯基硼酸酯、二烯和1，2-不饱和羰基的Z选择性交叉歧化反应。将引入催化剂，使化学家能够制备Z-二或三取代大环烯烃，而不必在多步全合成的后期阶段放弃近一半的有价值的原料作为不需要的立体异构体。新的催化剂和方法将产生通常被合成化学家视为“面包和黄油”的实体，但它们的制备往往需要漫长而不切实际的路线。将通过有效的方法合成具有重要生物学意义的分子，如抗突变镰刀菌二醇、抗病毒氯磺脂、细胞毒性二唑C1、赤霉素生物合成抑制剂Cladospolde B、抗菌和抗癌的nakadomarin A，以及抗癌药物epthilone B和neopeltolide，突出拟议研究中出现的概念、策略、催化剂和方案的特殊用途。

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.