盐酸川丁特罗代谢物的合成Synthesis of the metabolite of tradinterol hydrochloride
吕海亮,潘莉,李晓强,程卯生
L Hai-liang,PAN Li,LI Xiao-qiang,CHENG Mao-sheng
摘要(Abstract)：
目的研究新药盐酸川丁特罗进入大鼠体内后经独特的代谢途径生成特殊代谢产物的合成方法。方法以4-氨基-3-三氟甲基苯甲酸为起始原料,经氯代、甲基化、碘代、甲磺酰基化、溴代、还原、胺化得到目标化合物。结果经7步反应合成目标化合物,总收率为3%,目标化合物结构经1 H-NMR和MS确证。结论该化合物为盐酸川丁特罗代谢物研究提供物质支持。
Objective To study the synthesis of the particular metabolite of tradinterol hydrochloride and explain the specific metabolic pathways of tradinterol hydrochloride invivo.Methods The target compound was synthesized from4-amino-3-(trifluoromethyl)benzoic acid via the formation of acyl chloride and ketone,iodination,the substitution of methylsulfonyl,bromination,reduction,amination.Results The structure of the matebolite of tradinterol hydrochloride was confirmed by 1 H-NMR,MS,and the overall yield was 3%.Conclusions The synthesis of this metabolite gives support to the further study of the metabolite of tradinterol hydrochloride.
关键词(KeyWords)：
盐酸川丁特罗;代谢物;合成
tradinterol hydrochloride;metabolite;synthesis
基金项目(Foundation): 国家科学技术部十一五863计划基金资助项目(2006AA020604)
作者(Author):
吕海亮,潘莉,李晓强,程卯生
L Hai-liang,PAN Li,LI Xiao-qiang,CHENG Mao-sheng
DOI: 10.14066/j.cnki.cn21-1349/r.2013.09.015
参考文献(References)：
- [1]LI Kun-jie,QIN Feng,JING Li-juan,et al.In vivo and in vitro met abolism of a novelβ2-adrenoceptor agonist,trantinterol:metabolites isolation and identification by LC-MS/MS and NMR[J].Anal Bioanal Chem,2013,405:2619-2634.
- [2]CHENG Mao-sheng,PAN Li,JI Lei,et al.Novel Phenylethanolamine compouds having beta-2 acceptor excitatory function and their preparation method:EP,1439164A1[P].2004-07-21.
- [3]KRUGER G,KECK J,NOLL K,et al.Synthesis of further amino-halogen-subs-tituted phenyl-aminoethanols[J].Drug Res,1984,34(Ⅱ,11A):1612-1624.
- [4]YUAN Gao-qing,ZHENG Jun-hua,GAO Xiaofang,et al.Copper-catalyzed aerobic oxidation and cleavage/formation of C-S bond:a novel synthesis of aryl methyl sulfones from aryl halides and DMSO[J].Chem Commun,2012,48:7513-7515.
- [5]MA Da-wei,ZHU Wei.Synthesis of aryl sulfones via L-proline-promoted CuI-catalyzed coupling reaction of aryl halides with sulfinic acid salts[J].J Org Chem,2005,70:2696-2700.
- [6]SUZUKI H,ABE H.Copper-assisted displacement reaction of nonactivated iodoarenes with arenesulfinates.Convenient alternative synthesis of unsymmetrical diaryl sulfones[J].Tetrahedron Lett,1995,36(35):6239-6242.