烟碱化合物的固相合成研究  

Study on solid-synthesis of nicotine compounds

作　　者：冒德寿 汤琪琳 杨晶 尚娜 李振杰 刘志华 汤峨 MAO Deshou;TANG Qilin;YANG Jing;SHANG Na;LI Zhenjie;LIU Zhihua;TANG E(Yunnan Key Laboratory of Tobacco Chemistry,Technical Center of Yunnan China Tobacco Industry Co.,Ltd.,Kunming 650106,Yunnan,China;Key Laboratory of Medicinal Chemistry for Natural Resources,Ministry of Education and Yunnan Province,School of Pharmacy,Yunnan University,Kunming 650500,Yunnan,China)

机构地区：[1]云南省烟草化学重点实验室,云南中烟工业有限责任公司技术中心,云南昆明650106 [2]教育部自然资源药物化学重点实验室,云南大学药学院,云南昆明650500

出　　处：《云南大学学报（自然科学版）》2024年第3期521-526,共6页Journal of Yunnan University(Natural Sciences Edition)

基　　金：云南省烟草化学重点实验室开放课题(2021539200340241);云南省科技厅基础研究计划(201901BB050018,202301BF070001-011);国家自然科学基金(22161050)。

摘　　要：开发了一种高效的烟碱化合物的固相合成新方法.利用交联聚苯乙烯负载磺酸树脂,经树脂氯化,制备出聚苯乙烯负载磺酰氯树脂作为固载有机硫试剂.从3-溴吡啶出发,经锂化酰化、羰基还原、羟基磺酰化、磺酸酯胺化环化4步反应,合成了5个烟碱类化合物,总产率为52%~66%,产物结构经1H NMR鉴定确认.方法具有产率高、操作简单,树脂可以回收再用,具有工业自动化生产的应用前景等特点.In this paper,a new method for the efficient solid-phase synthesis of nicotine compounds has been developed.A polystyrene-supported sulfonyl chloride resin was prepared from cross-linked polystyrene-supported sulfonic acid resin as a solid-phase organosulfur reagent.Starting from 3-bromopyridine,five nicotine compounds were synthesized by four-step reactions including lithiation/acylation of pyridine,reduction of carbonyl group,sulfonylation of hydroxyl group,and amination/cyclization of sulfonate with overall isolated yields of 52%−66%,and the structures of the synthesized nicotine compounds were identified by 1H NMR.The method features high yields,simple operation,recycling and reuse of the resin,and the prospect of application in industrial automation production.

关 键 词：烟碱 固相合成 交联聚苯乙烯 有机硫试剂 

分 类 号：Q626.2[生物学—生物物理学] TQ453.299[化学工程—农药化工]