含噻吩并[3,2-c]吡啶α-氨基膦酸酯类衍生物的合成及生物活性的研究  

Synthesis and Biological Activities of α-Aminophosphonates Derivatives Containing Thieno[3,2-c]pyridine

作　　者：马姣丽[1] 朱文娟[1] 李静[1] 纪朋 朱智志 廖新成[1] 

机构地区：[1]郑州大学化学与分子工程学院,郑州450052 [2]河南中烟工业有限责任公司,郑州450016

出　　处：《有机化学》2013年第7期1472-1477,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.21171149)资助项目~~

摘　　要：以3-噻吩甲醛和氨基乙醛缩二甲醇为原料,经亲核加成、还原、取代、成环、甲酰化反应,得到2-醛基噻吩并[3,2-c]吡啶(4),然后与亚磷酸酯、芳香胺发生类Mannich反应得到一系列新型含有噻吩并[3,2-c]吡啶环的α-氨基膦酸酯类衍生物6a～6p.所有目标化合物的结构均经1H NMR,13C NMR,31P NMR,IR和MS确证.初步的生物活性测定试验表明,在50 ug/mL浓度下,大部分目标化合物对食管癌细胞(EC109)、人体肝癌细胞(HepG2)表现出较好的抑癌活性,其中化合物6k和6o对人体肝癌细胞的抑制率超过90%.A series of novel α-aminophosphonate derivatives containing thieno[3,2-c]pyridine(6a～6p),which have never been reported in literature,were synthesized from thieno[3,2-c]pyridine-2-carbaldehyde,phosphate ester and aromatic amine by the Mannich-type reaction.Thieno[3,2-c]pyridine-2-carbaldehyde(4) was produced via nucleophilic addition reaction,reduction,substitution reaction,cyclization,formylation using 3-thiophene formaldehyde and 2,2-dimethoxyethanamine as the starting material.The structures of all compounds have been confirmed by 1H NMR,13C NMR,31P NMR,IR and MS techniques.The preliminary results of biological tests indicated that most of the title compounds exhibit relatively good anticancer activity against EC109,HepG2 at the concentration of 50 μg/mL,especially compounds 6k and 6o have more than 90% inhibitory rate against HepG2

关 键 词：Α-氨基膦酸酯 噻吩并[3 2-c]吡啶 合成 

分 类 号：O626[理学—有机化学]