Department of Chemistry and Biochemistry, University of Denver , Denver, Colorado 80208, United States.
J Am Chem Soc. 2017 Nov 22;139(46):16584-16590. doi: 10.1021/jacs.7b07598. Epub 2017 Nov 9.
Atom- and step-economy in photoassisted diversity-oriented synthesis (DOS) is achieved with a versatile oxalyl linker offering rapid access to complex alkaloid mimics in very few experimentally simple steps: (i) it allows for fast tethering of the photoactive core to the unsaturated pendants, especially important in the case of (hetero)aromatic amines-essentially a one-pot reaction with no isolation of intermediates; (ii) the α-dicarbonyl tether acts as a chromophore enhancer, extending the conjugation chain and facilitating the "harvest" of the lower energy photons for the primary and secondary photoreactions; (iii) it enhances the quantum yield of intersystem crossing (ISC), i.e., it is capable of sensitizing secondary photochemical processes in the cascade; and (iv) the tether forms an additional heterocyclic moiety, imidazolidine-4,5-dione, a known pharmacophore. The overall photoassisted cascade is an efficient complexity-building process as quantified by computed step-normalized complexity indices, leading to extended polyheterocyclic molecular architectures comparable in complexity to natural products such as paclitaxel while requiring only 2-4 simple synthetic steps from readily available chemical feedstock.
在光辅助的多样性导向合成（DOS）中实现了原子经济性和步骤经济性，这得益于多功能的草酰基连接体，它能够快速将光活性核心连接到不饱和侧链上，特别是对于（杂）芳族胺，这是非常重要的，因为它基本上是一个一锅反应，无需分离中间体；（ii）α-二羰基连接体充当发色团增强剂，延长了共轭链，并促进了初级和次级光反应中低能量光子的“收获”；（iii）它增强了系间窜跃（ISC）的量子产率，也就是说，它能够敏化级联中的次级光化学反应；（iv）连接体形成了一个额外的杂环部分，即咪唑烷-4,5-二酮，这是一种已知的药效团。整个光辅助级联是一个高效的复杂度构建过程，如通过计算步骤归一化复杂度指数来量化，得到了扩展的多杂环分子结构，其复杂度可与紫杉醇等天然产物相媲美，而只需从易得的化学原料中进行 2-4 个简单的合成步骤。
