固体Lewis酸脱N-苄基制备D-生物素Ⅰ

Preparation of D-biotinⅠby removal of N-benzyl with solid Lewis acid

为了解决由双苄基生物素Ⅱ通过氢溴酸脱苄和关环两步反应制备D-生物素Ⅰ所引起的高能耗、高污染、毒性大的问题,以双苄基生物素Ⅱ为原料,一步法制备了D-生物素Ⅰ。对固体Lewis酸和溶剂种类、Lewis酸与双苄基生物素Ⅱ的物质的量比、反应温度和反应时间进行了优化,确定了最佳反应条件。利用FTIR、NMR、HPLC、LC-MS对产物结构进行了确证。结果表明,Lewis酸为氯化铝、溴化铝、氯化锌、溴化锌,溶剂为三氟甲苯,n(Lewis酸)∶n(双苄基生物素Ⅱ)=2∶1,反应温度为70~75℃,反应时间为2 h时,产物收率可达90%以上,HPLC纯度达到99.0%以上。

A one step method was employed to synthesize D-biotin Ⅰ from dibenzyl biotin Ⅱ in order to solve the problems of high energy consumption,pollution and toxicity caused by the two-step reaction of debenzyl hydrobromate and ring closure.Optimal reaction conditions were identified via optimization solid Lewis acid type and solvent type,molar ratio of Lewis acid to dibenzyl biotin Ⅱ,reaction temperature and reaction time,followed by product structural characterization by FTIR,NMR,HPLC and LC-MS.The results showed that the product yield was higher than 90% and HPLC purity reached over 99.0% when using aluminum chloride,aluminum bromide,zinc chloride and zinc bromide as Lewis acid,trifluoromethyl as solvent,and n(Lewis acid)∶n(dibenzyl biotin Ⅱ)kept at 2∶1,reaction temperature at 70~75℃ and reaction time for 2 h.