摘要
艾地骨化醇原料药在酸性、碱性、氧化、光照和高温条件下进行强制降解试验,生成(1R,2R,3R,5Z,7E)-2-(3-羟基丙氧基)-9,10-开环胆甾-5,7,10(19),24(25)-四烯-1,3-二醇(AD-1)、(1R,2R,3R,5E,6Z,8Z)-2-(3-羟基丙氧基)-9,10-开环胆甾-5(10),6,8(9)-三烯-1,3,25-三醇(AD-2)、(1 R,2R,3R,5E,7E)-2-(3-羟基丙氧基)-9,10-开环胆甾-5,7,10(19)-三烯-1,3,25-三醇(AD-3)、(1R,2R,3R,5E,6E,8Z)-2-(3-羟基丙氧基)-9,10-开环胆甾-5(10),6,8(9)-三烯-1,3,25-三醇(AD-4)和(1R,2R,3R,14S,5E,6Z,8Z)-2-(3-羟基丙氧基)-9,10-开环胆甾-5(10),6,8(9)-三烯-1,3,25-三醇(AD-5)这 5 种降解产物.其中,AD-1和AD-5未见文献报道.该文合成了 AD-1和AD-5,并优化了 AD-4的合成工艺,产物经1H NMR、13C NMR和MS结构确证.文章为艾地骨化醇的质量研究提供了一定的参考,同时为其生产、包装、贮存提供了依据.
Abstract
Forced degradation tests of eldecalcitol API were conducted under acidic,alkaline,oxidative,light-exposed,and high-temperature conditions.Five degradation products were generated,namely(1R,2R,3R,5Z,7E)-2-(3-hydroxypropoxy)-9,10-secocholesta-5,7,10(19),24(25)-tetraene-1,3-diol(AD-1),(1R,2R,3R,5E,6Z,8Z)-2-(3-hydroxypropoxy)-9,10-secocholesta-5(10),6,8(9)-triene-1,3,25-triol(AD-2),(1R,2R,3R,5E,7E)-2-(3-hydroxypropoxy)-9,10-secocholesta-5,7,10(19)-triene-1,3,25-triol(AD-3),(1R,2R,3R,5E,6E,8Z)-2-(3-hydroxypropoxy)-9,10-secocholesta-5(10),6,8(9)-triene-1,3,25-triol(AD-4)and(1R,2R,3R,14S,5E,6Z,8Z)-2-(3-hydroxypropoxy)-9,10-secocholesta-5(10),6,8(9)-triene-1,3,25-triol(AD-5).Among them,AD-1 and AD-5 were not found in literatures.This study developed synthetic routes for AD-1 and AD-5,and optimized the synthesis process for AD-4.The structures of these products were confirmed by 1H NMR,13C NMR,and MS.This paper provides the references for the quality research of eldecalcitol,as well as its production,packaging,and storage.
基金项目
泰山产业领军人才工程项目(tscx202211121)
维普
万方数据