KRN7000的合成研究

Study on the Synthesis of KRN7000

选取2,3,4,6-四-氧-苄基-α-D-半乳吡喃糖硫苷1作为糖基供体,与2-(N-二十六烷酰基氨基)-3,4-二-O-苯甲酰基-植物鞘氨醇2反应合成α-半乳糖神经酰胺(KRN7000)的骨架,进而通过两步脱保护反应得到重要的药物分子KRN7000,总收率为57.3%。充分探究了投料比、催化剂用量和温度对糖基化反应收率的影响。实验结果表明,当n(2)∶n(1)∶n(NIS)∶n(TMSOTf)=1∶1.5∶2∶0.1,温度为0℃时,糖基化收率可达61%。同时探究了溶剂对脱苄基保护反应的影响。溶剂为二氯甲烷/甲醇混合溶剂时,收率定量。该路线具有原料易得、操作简单、收率高等优点,为KRN7000类似物的合成提供了一种新的方法。

The skeleton ofα-galactoseramide(KRN7000)is synthesized by 2,3,4,6-tetra-O-benzyl-α-D-galactopyranoside 1(glycosyl donor)and 2-(N-hexadecanoylamino)-3,4-Di-O-benzoyl-phytosphingosine 2(glycosyl receptor).Then the target drug molecule KRN7000 is synthesized through a two-step deprotection reaction,the total yield is 57.3%.The effects of molar ratio,amount of catalyst and temperature on the yield of glycosylation are fully explored.The experimental results show that,n(2)∶n(1)∶n(NIS)∶n(TMSOTf)=1∶1.5∶2∶0.1,the temperature is 0℃,the yield of glycosylation can reach 61%.At the same time,the influence of the solvent on the debenzyl reaction is explored.When the solvent is a dichloromethane/methanol mixed solvent,the yield is quantitative.This route has the advantages of readily available raw materials,simple operation and high yields.It provides a new method for the synthesis of KRN7000 analogs.