艾氟康唑相关物质的合成  

Synthesis of Related Substance of Efinaconazole

作　　者：李晓坤[1] 张灵帅[1] 孟迪[1] 

机构地区：[1]河南中医药大学药学院,河南郑州450046

出　　处：《化学试剂》2017年第1期100-102,106,共4页Chemical Reagents

摘　　要：为控制抗真菌药艾氟康唑的产品质量,合成了(2S,3R)-2-(2,4-二氟苯基)-3-(4-亚甲基哌啶-1-基)-1-(1H-1,2,4-三唑-1-基)-2-丁醇(艾氟康唑非对映异构体)。首先,以L-乳酸甲酯为原料合成了中间体(2S)-1-(2,4-二氟苯基)-2-(3,4,5,6-四氢-2H-吡喃-2-氧)丙烷-1-酮,然后经脱保护、哌啶烷基化得中间体(2R)-1-(2,4-二氟苯基)-2-(4-亚甲基哌啶-1-基)丙烷-1-酮,经科里-柴可夫斯基环氧化、三氮唑烷基化后得目标化合物。该合成路线未见报道,所有化合物经1HNMR和ESI-MS确证结构。该相关化合物可作为艾氟康唑质量控制中的杂质对照,用于准确定量、定性分析相关杂质。To perform the quality control of the antifungal drug efinaconazole,the diastereoisomer of efinaconazole（2S,3R）-2-（2,4-difluorophenyl）-3-（4-methylenepiperidin-1-yl）-1-（1H-1,2,4-triazol-1-yl） butan-2-ol was prepared.Intermediate（2S）-1-（2,4-difluorophenyl）-2-（tetrahydro-2H-pyran-2-yloxy） propan-1-one was first prepared from L-methyl lactate based on the reference,then the ketone（2R）-1-（2,4-difluorophenyl）-2-（4-methylenepiperidin-1-yl） propan-1-one was offered via the deprotection and alkylation reaction,finally the product was obtained after the subsequent Corey-Chaykovsky epoxidation and triazole alkylation.It is the first time to report this route for synthesis of the product.The structures were comfirmed by ~1HNMR and ESIMS.This substance can be used as the reference substance of the impurity in the quality control of efinaconazole.

关 键 词：抗真菌药 艾氟康唑 相关物质 合成 

分 类 号：R914.5[医药卫生—药物化学]