Synthesis of 7-methyl-6-indolopterin and 7-methyl-6-indoloquinoxaline

The first syntheses of indolopterin and indoloquinoxaline, two important and dissimilar diheterocycles linking C-2 of indole with C-6 of pterin (significant positions for showing biological activity), and quinoxaline, respectively, have been achieved based on two classical reactions. The introduction of a keto methyl group on to the 6-position of pterin and quinoxaline followed by Fischer indole synthesis led to these target diheterocycles. These indole-substituted diheterocycles will significantly increase the electron density on the pterin-5-N and quinoxazoline-2-N, which may change the redox properties of pterin and quinoxaline, and also the electron-withdrawing pterin or quinoxazoline should make the indole NH more acidic.

本研究基于两类经典反应，首次实现了吲哚蝶呤（indolopterin）与吲哚喹喔啉（indoloquinoxaline）这两种重要且结构迥异的双杂环化合物的全合成：二者分别以吲哚C-2位点与蝶呤（pterin）C-6位点、吲哚C-2位点与喹喔啉（quinoxaline）C-6位点相连，而该类连接位点正是展现生物活性的关键位置。先在蝶呤与喹喔啉的6位引入酮甲基，再经费舍尔吲哚合成法（Fischer indole synthesis）处理，即可得到上述目标双杂环产物。此类吲哚取代的双杂环化合物可显著提升蝶呤-5-N与喹唑啉（quinoxazoline）-2-N上的电子云密度，这或可改变蝶呤与喹喔啉的氧化还原特性；同时，具备吸电子特性的蝶呤或喹唑啉单元也将使吲哚NH的酸性增强。