Shin Yongje, Yoo Changho, Moon Youngtaek, Lee Yunho, Hong Sungwoo
Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 305-701 (Korea); Center for Catalytic Hydrocarbon Functionalization, Institute for Basic Science (IBS), Daejeon, 305-701 (Korea).
Chem Asian J. 2015 Apr;10(4):878-81. doi: 10.1002/asia.201402876. Epub 2014 Sep 22.
Frutinone A, a biologically active ingredient of an antimicrobial herbal extract, demonstrates potent inhibitory activity towards the CYP1A2 enzyme. A three-step total synthesis of frutinone A with an overall yield of 44 % is presented. The construction of the chromone-annelated coumarin core was achieved through palladium-catalyzed CH carbonylation of 2-phenolchromones. The straightforward synthetic route allowed facile substitutions around the frutinone A core and thus rapid exploration of the structure-activity relationship (SAR) profile of the derivatives. The inhibitory activity of the synthesized frutinone A derivatives were determined for CYP1A2, and ten compounds exhibited one-to-two digit nanomolar inhibitory activity towards the CYP1A2 enzyme.
弗鲁蒂诺酮A是一种具有抗菌活性的草药提取物中的生物活性成分，对CYP1A2酶具有强大的抑制活性。本文介绍了一种三步全合成弗鲁蒂诺酮A的方法，总产率为44%。通过钯催化的2-苯酚色酮的CH羰基化反应构建了色酮稠合香豆素核心。这条直接的合成路线使得在弗鲁蒂诺酮A核心周围能够轻松进行取代反应，从而快速探索衍生物的构效关系（SAR）概况。测定了合成的弗鲁蒂诺酮A衍生物对CYP1A2的抑制活性，十种化合物对CYP1A2酶表现出一到两位数的纳摩尔抑制活性。
