Catalytic Stereoselective Olefin Metathesis Reactions

描述（由申请人提供）：烯烃存在于大量生物活性分子中，并用于获得它们的一些最广泛使用的转化（如氢化、环氧化、硼氢化、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或更高能量的Z异构体存在。因此，允许以高选择性和具有成本效益的方式有效、可靠地获得每种异构体形式的方法对化学、生物学和医学具有重要意义。特别有价值的是用于立体选择性形成烯烃的催化方法;然而，这样的方法是不常见的。特别稀缺的是提供Z烯烃的催化方案。该计划的研究重点是设计，合成和开发一系列钼和钨基催化剂，这些催化剂可用于烯烃合成最强大和最有效的方法之一：催化烯烃复分解。最初在这个NIH资助的项目中构思的各种概念将用于引入可以在空气中操作的催化剂，但当在底物存在下放置在溶液中时，提供卓越的反应性和选择性。这种催化剂将使化学家能够获得完全无法达到的反应性和/或选择性水平。将开发促进烯丙基醚、环氧化物、硼酸酯、硅烷以及乙烯基硼酸酯、二烯和1，2-不饱和羰基的Z-选择性交叉复分解反应的烯烃复分解催化剂。催化剂将被引入，这将允许化学家制备Z二或三取代的大环烯烃，而不必在多步全合成的后期阶段作为不希望的立体异构体而丧失其近一半的有价值的材料。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，但它们的制备通常需要漫长而不切实际的路线。将出现从拟议的调查的概念，战略，催化剂和协议的特殊用途将突出通过有效的方法来合成的生物学上重要的分子，如抗突变falcarindiol，抗病毒chlorosufolipids，细胞毒性disorazole C1，赤霉素生物合成抑制剂枝孢菌素B，抗菌和抗癌nakadomarin A，和抗癌剂埃坡霉素B和neopeltolide。

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.