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从色醇出发,通过Sharpless环氧化、酰胺化、偶联和成盐四步反应合成了一系列新型的吲哚并四氢呋喃-咪唑盐杂合物,其结构经~1H NMR,~(13)CNMR,HRMS以及X射线单晶衍射确定.对合成的新化合物进行了体外抗肿瘤细胞毒活性筛选,结果表明,1-((3aR,8aS)-3,3a-二氢-3a-羟基-2H-呋喃并[2,3-b]吲哚-8(8aH)-基)乙酮-3-(2-(萘-2-基)-2-氧乙基)-5,6-二甲基-1H-苯并[d]咪唑-3-溴盐(20)和1-((3aR,8aS)-3,3a-二氢-3a-羟基-2H-呋喃并[2,3-b]吲哚-8(8aH)-基)乙酮-3-(2-萘甲基))-5,6-二甲基-1H-苯并[d]咪唑-3-溴盐(22)具有较好的体外肿瘤生长抑制活性,对SMMC-7721、MCF-7和SW-480肿瘤细胞株的活性均优于顺铂(DDP),1-((3aR,8aS)-3,3a-二氢-3a-羟基-2H-呋喃并[2,3-b]吲哚-8(8a H)-基)乙酮-3-(2-溴苄基))-5,6-二甲基-1H-苯并[d]咪唑-3-溴盐(24)对SW-480肿瘤细胞株表现出较好的选择性细胞毒活性,其IC_(50)值约为顺铂的2.0倍.
Starting from the color alcohol, a series of novel indole-tetrahydrofuran-imidazolate complexes were synthesized by the Sharpless epoxidation, amidation, coupling and salt-formation reactions. Their structures were confirmed by ~ 1H NMR, CNMR, HRMS and single crystal X-ray diffraction.It was shown that 1 - ((3aR, 8aS) -3,3a-dihydro-3a-hydroxy-2H -furo [2,3-b] indol-8 (8aH) -yl) ethanone -3- (2- (naphthalen- 2-yl) -2-oxoethyl) Benzo [d] imidazole-3-bromide (20) and 1 - ((3aR, 8aS) -3,3a- dihydro-3a-hydroxy-2H- furo [2,3- b] (8aH) -yl) ethanone -3- (2-naphthylmethyl) -5,6-dimethyl-1H-benzo [d] imidazole-3- The activity of SMMC-7721, MCF-7 and SW-480 tumor cell lines was better than that of cisplatin (DDP), 1 - ((3aR, 8aS) -3,3a-dihydro-3a Hydroxy-2H-furo [2,3-b] indol-8 (8aH) -yl) ethanone -3- (2-bromobenzyl) The [d] imidazole-3-bromide salt (24) showed good selective cytotoxic activity against SW-480 tumor cell lines with an IC 50 value about 2.0-fold that of cisplatin.