Pertejo Pablo, Peña-Calleja Pablo, Carreira-Barral Israel, Quesada Roberto, Alejandro Cordero Nicolás, Javier Rodríguez Francisco, García-Valverde María
Department of Chemistry, Faculty of Science, University of Burgos, 09001, Burgos, Spain.
Org Biomol Chem. 2017 Sep 20;15(36):7549-7557. doi: 10.1039/c7ob01807j.
Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) and other benzo-fused N-heterocycles constitute privileged structures found in numerous bioactive compounds. Thus, developing simple and selective syntheses to furnish these derivatives from easily accessible starting materials is an important and challenging goal. In this work, novel pyrrolobenzodiazepine and pyrroloquinazoline derivatives have been synthesized following a common two step synthetic strategy. This strategy involves a one-pot Ugi/cyclization sequence followed by a reduction with spontaneous thermocontrolled cyclization. The control of the temperature in this second step allows fully selective access to either pyrrolo[2,1-c][1,4]benzodiazepine-3-ones 6 or pyrrolo[2,1-b]quinazolines 7. Density functional theory (DFT) calculations have been carried out to rationalize this reactivity, identifying the kinetic and thermodynamic reaction products and offering insights into the cyclization pathways. These synthetic methodologies show the versatility of the Ugi reaction as a tool in the synthesis of heterocyclic compounds with a pseudopeptidic skeleton.
吡咯并[2,1-c][1,4]苯并二氮杂卓（PBDs）和其他苯并稠合的氮杂环构成了众多生物活性化合物中存在的优势结构。因此，开发从易于获取的起始原料制备这些衍生物的简单且选择性的合成方法是一个重要且具有挑战性的目标。在这项工作中，遵循一种常见的两步合成策略合成了新型吡咯并苯并二氮杂卓和吡咯并喹唑啉衍生物。该策略包括一锅法Ugi/环化序列，随后进行还原并伴有自发的热控环化。第二步中温度的控制使得能够完全选择性地得到吡咯并[2,1-c][1,4]苯并二氮杂卓-3-酮6或吡咯并[2,1-b]喹唑啉7。已进行密度泛函理论（DFT）计算以合理化这种反应性，确定动力学和热力学反应产物，并深入了解环化途径。这些合成方法展示了Ugi反应作为合成具有假肽骨架的杂环化合物工具的多功能性。
