Department of Chemistry, University of Chicago, 5735 South Ellis Avenue, Chicago, Illinois 60637, United States.
J Am Chem Soc. 2020 Jul 15;142(28):12027-12033. doi: 10.1021/jacs.0c04914. Epub 2020 Jul 2.
Among defensive alkaloids isolated from ladybugs, the heterodimeric member chilocorine C possesses an alluring monomeric unit that combines quinolizidine and indolizidine substructures. Indeed, the overall stereochemical disposition of its ring fusions is distinct from those of related natural products. Herein we show that a carefully orchestrated sequence with several chemoselective transformations, including a designed cascade that accomplishes nine distinct chemical reactions in one-pot, can smoothly forge that domain and ultimately enable a 15-step, 11-pot enantiospecific synthesis of the natural product. Mechanistic studies, density functional theory calculations, and the delineation of several other unsuccessful approaches highlight its unique elements.
在从瓢虫中分离出的防御性生物碱中，异二聚体成员 chilocorine C 具有诱人的单体单元，它结合了喹诺利定和吲哚利定亚结构。事实上，其环融合的整体立体化学排列与相关天然产物不同。在这里，我们展示了一个精心设计的序列，其中包括几个化学选择性转化，包括一个设计的级联反应，可在一锅反应中完成九个不同的化学反应，可以顺利地构建该结构域，并最终实现 15 步、11 个步骤的对映选择性合成天然产物。机理研究、密度泛函理论计算以及对几种其他不成功方法的描述突出了其独特的元素。
