BMN-673类似物的合成  

Synthesis of BMN-673 Analogues

作　　者：杨梦然 胡旭 冯权武 吴莉[1] 傅晶[1] 尹传奇[1] YANG Mengran;HU Xu;FENG Quanwu;WU Li;FU Jing;YIN Chuanqi(School of Chemical and Environmental Engineering,Wuhan Institute of Technology,Wuhan 430205,China;Hubei Huisheng Pharmaceutical Co.,Ltd,Xianning 437000,China)

机构地区：[1]武汉工程大学化学与环境学院,湖北武汉430205 [2]湖北惠生药业有限公司,湖北咸宁437000

出　　处：《武汉工程大学学报》2019年第1期25-34,共10页Journal of Wuhan Institute of Technology

基　　金：湖北省教育厅重点项目(D20141510);湖北省教育厅项目(D2017053)

摘　　要：以6-氟-4-硝基-3H-异苯并呋喃-1-酮为原料,与醛R1=1-methyl-1H-1,2,4-triazol-5-yl,4-flurophenyl,phenyl,4-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)phenyl(R1CHO)经亲核加成、内酯开环反应得到4个酮酯化合物,随后与醛R2=3-bromophenyl,benzofuran-6-yl,1H-indole-6-yl,7-bromobenzo[1,3]dioxole-5-yl,1,4-benzodioxin-6-yl,benzo[d][1,3]dioxol-5-yl(R2CHO)经羟醛缩合、环化反应得到九个新的BMN-673类似物,反应总收率为33%～48%。所有化合物结构经核磁共振氢谱、核磁共振碳谱、质谱和元素分析进行表征并得到确认。优化了亲核加成反应条件,结果表明,以1,4-二氧六环为溶剂,反应时间从10 h缩短至4 h,收率达80%～90%。Four keto-ester compounds were firstly prepared by nucleophilic addition and lactone ring-opening of6-fluoro-4-nitro-3H-isobenzofuran-1-one with aldehydes R1=1-methyl-1H-1,2,4-triazol-5-yl,4-flurophenyl,phenyl and 4-(4-cyclopropanecarbonyl-piperazine-1-carbonyl)phenyl(R1CHO).And then nine novel BMN-673 analogues were produced by aldol condensation and cyclization of the keto-ester compounds with aldehydes R2=3-bromophenyl,benzofuran-6-yl,1H-indol-6-yl,7-bromobenzo[1,3]dioxol-5-yl,1,4-benzodioxin-6-yl andbenzo[d][1,3]dioxol-5-yl(R2CHO).The overall yields of the analogues range from33%to 46%,and themolecular structures of the synthesized compounds are confirmed by1 H and13C nuclear magnetic resonancespectroscopy,mass spectrometry and elemental analysis.The results of optimizing condition of nucleophilicaddition show that the reaction time reduces from 10 h to 4 h and the yield is up to 80%-90%with 1,4-dioxaneas the solvent.

关 键 词：BMN-673类似物 6-氟-4-硝基-3H-异苯并呋喃-1-酮 亲核加成反应 内酯开环反应 羟醛缩合反应 环化反应 

分 类 号：O621[理学—有机化学]