用'点击化学'法合成新型他克林-四氢异喹啉异二联体

摘要

从2-氯乙胺盐酸盐出发,经叠氮化与缩合反应制得9-(叠氮基乙基氨基)-1,2,3,4-四氢吖啶类衍生物(4a～4c);以6-庚炔-1-醇为原料,利用微波反应合成了2-(6.庚炔基)-6,7-二甲氧基-1-苯基-1,2,3,4-四氢异喹啉(7);4与7通过"点击化学"法合成了三个乙酰胆碱酯酶抑制剂-3个他克林-四氢异喹啉异二联体(1a～1c),其结构经NMR和HR-MS表征,其中1b和1c未见文献报道.%9-(Triazo-ethylamino) -1,2,3,4-tetrahydro-acridine derivatives ( 4a～4c ) were prepared from 2-chloroethylamine hydrochloride by the reaction with sodium azide, then condensation with 9-chlor-1,2,3,4 -tetrahydro-acridine derivatives, respectively. 2- ( Hept-6 -ynyl) -6,7 -dimethoxy-1 -phenyl-l,2,3,4-tetrahydroisoquinoline (7) was synthesized by the reaction of 6-heptine-1 -ol with POCl3,NaI and 6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline under microwave radiation, respectively. Three acetylcholinesterase inhibitors, tacrine-tetrahydroisoquinoline hybrids ( la～lc), were synthesized from 4 and 7 by click chemistry method. The structures were characterized by NMR and HR-MS. 1b and 1c were new compounds.