Progress in the Synthesis of Cinnoline Derivatives

Abstract

Cinnolines are "privileged scaffold" in new material and drug research, and development for their extensive biological activities such as anticancer, antibacterial, antiviral, anti-inflammatory, and sedative activities and good electron-accepting ability. As a result, the development of new synthetic routes to this important structure has been actively investigated in recent years. Especially, the C-H functionalization strategy has promoted the development of new methods greatly. The recent advances of the synthetic methods to cinnolines based on different synthetic strategies and raw materials are reviewed. Keywords cinnolines; C-H functionalization; coupling; tandem reaction 苯并[c]哒嗪(benzo[c]pyridazine), 俗称噌啉(cinnoline), 是一类重要的含氮有机杂环化合物(以下统称噌 啉). 噌啉本身具有细胞毒性, 对 Escherichia coli 菌种的 生长有抑制作用 [1] , 引入取代基或并环结构的噌啉衍生 物展现出更为广泛的生物活性 [2] , 例如抗癌(1) [3] 、抗菌 (2) [4] 、 抗病毒(3) [5] 、 抗炎(4) [6] 和镇静作用(5)

1H-Benzo[de]cinnolines: an interesting class of heterocycles

“…Simple 1H-benzo[de]cinnolines have been prepared by Lacy and Smith, Scheme 1(a) 5 and 1(b), 6 and by Aksenov, Aksenova et al, 7 Scheme 1(c). Using the methods represented in Scheme 1(a), a series of 1H-benzo[de]cinnolines have been prepared (Figure 2) by Mezheritskii et al, [8][9][10][11][12][13] A totally different method has been reported by Chenoweth et al, 8 (cited in 9 ). A very complex and beautiful reaction, starting from 3,6-dimethyl-1,2,4,5-tetrazine and o-benzyne, allows to prepare compound 20, 4-methyl-6-phenyl-6H-dibenzo[de,g]cinnolin 10 They have prepared a large set of compounds, 20-32, and some dimethyl derivatives starting from 4,5-dimethyl-o-benzyne (Scheme 2).…”

“…These values will be compared with the calculated chemical shifts (Section 6). Like most recent papers, the experimental part contains 1 H NMR [9][10][11][12][13]30,31,[37][38][39]44 and 13 C NMR 11,37,43 data. 15 N NMR data are however still scarce 37 (see Section 7).…”