Development of New Cascade Sequences for the Construction of Novel Chemical Structures

有机合成项目支持王功教授在西弗吉尼亚大学的研究，研究新的级联反应序列，从而构建新的化学结构。基于烯二炔和烯烯环芳构化的反应序列，包括(Z)-3-己烯-1,5-二炔和(Z)-1,2,4-庚三烯-6-炔，导致多环碳框架，而类似的烯烯酮、烯烯亚胺、烯异氰酸酯和烯碳二酰亚胺的环芳构化则提供了新的多环杂环。双二炔的级联电环化反应产生活性苯并环丁二烯，其不寻常的多环二聚体代表了含有多个二苯并环四烯单元的化合物的合成入口。烯二烯的环化导致邻喹二甲烷的形成，并可能发现新的合成途径，形成甾酮和四环结构，形成一些天然存在的二萜的基础。自然界的许多生物活性化合物都显示出复杂的分子结构，无论是为了结构阐明、大规模生产稀缺的天然化合物，还是为了制备下一代合成类似物，都需要不断发展新的策略来处理它们的分子复杂性。通过利用缺乏电子前体分子的不寻常的环化反应，王教授开发了多种含全碳原子的多环分子结构以及在其环结构中含有氮和氧原子的化合物的简易合成路线。从化学的角度来看，这些环化反应本身就很重要，解决了有机结构和反应性方面的基本问题。此外，反应化学提供了已知的和新的化学结构的合成途径，为类固醇的制备提供了新的合成途径，如雌酮，以及其他四环结构的特征，一类天然存在的化合物被称为二萜。

The Organic Synthesis Program supports Professor Kung Wang's studies at the University of West Virginia of new cascade reaction sequences leading to the construction of novel chemical structures. Reaction sequences based on the cycloaromatization of enediynes and enyne-allenes, including (Z)-3-hexene-1,5-diynes and (Z)-1,2,4-heptatriene-6-ynes, lead to polycyclic carbon frameworks, while analogous cyclizations of enyne-ketenes, enyne-ketenimines, enyne-isocyanates, and enyne-carbodiimides afford access to novel polycyclic heterocycles. Cascade electrocyclizations of dienediynes provide reactive benzocyclobutadienes, the unusual polycyclic dimers of which represent synthetic entry to compounds containing multiple dibenzocyclooctatetraene units. Cyclizations of enediallenes lead to the formation of o-quinodimethanes and to the potential discovery of novel synthetic routes to estrone and tetracyclic structures forming the basis of a number of naturally-occurring diterpenes. Many of Nature's biologically active compounds display complex molecular structures, and the attempted synthesis of such compounds, whether for purposes of structure elucidation, large-scale production of scarce naturally occurring compounds, or preparation of next-generation synthetic analogs, requires the continuing development of new strategies to deal with their molecular complexity. By exploiting unusual cyclization reactions of electron-deficient precursor molecules, Professor Wang develops facile synthetic routes to a wide variety of polycyclic molecular structures containing all-carbon atoms as well as compounds containing nitrogen and oxygen atoms within their cyclic structures. These cyclization reactions are significant in their own right from a chemical perspective, addressing issues of fundamental importance with regards to organic structure and reactivity. Additionally, the reaction chemistry provides synthetic access to both recognized and novel chemical structures, affording new synthetic routes for the preparation of steroids such as estrone as well as other tetracyclic structures characteristic of a class of naturally-occurring compounds known as the diterpenes.