University of Bordeaux , Institute of Molecular Sciences, UMR-CNRS 5255, 351 cours de la libération, 33405 Talence, France.
Org Lett. 2015 Sep 18;17(18):4518-21. doi: 10.1021/acs.orglett.5b02218. Epub 2015 Sep 8.
The first total synthesis of eucophylline was reported in 10 steps and 10% overall yield. The naphthyridine core of eucophylline was prepared through the coupling between a strained azabicyclo[3.3.1]nonan-2-one and a trisubstituted benzonitrile, followed by a cyclization of the corresponding amidine. This coupling reaction was shown to proceed through a stable bicyclic chloroenamine intermediate. The azabicyclo[3.3.1]nonan-2-one skeleton was in turn accessible through a straightforward sequence including a free-radical three-component olefin carbo-oximation as a key step.
首次以 10 步和 10%的总收率完成了 eucophylline 的全合成。通过刚性氮杂双环[3.3.1]壬烷-2-酮与三取代苯甲腈的偶联，随后对相应的脒进行环化反应，制备得到 eucophylline 的萘啶核。该偶联反应显示通过稳定的双环氯亚胺中间体进行。氮杂双环[3.3.1]壬烷-2-酮骨架则可以通过包括自由基三组分烯烃碳氧肟化作为关键步骤的简单序列获得。
