甘露糖苷酶抑制剂Kifunensine的改进合成方法

An Improved Synthetic Approach to Mannosidase Inhibitor — Kifunensine

Kifunensine是一种从名为Kitasatosporia kifunense的放线菌中分离出来的生物碱,它是一种中性、稳定的化合物,同时也是甘露糖苷酶I的有效抑制剂,目前被广泛用于药物研发领域,具有很高的商业价值,但是它的合成制备非常困难,存在收率低、合成成本高等问题。本文对其合成方法进行了研究,以廉价易得的L-古洛糖酸-γ-内酯为原料,经过一系列转化得到Kifunensine。该操作中多个步骤可以用一锅法投料,操作简便,总产率为4. 8%。本文的方法为Kifunensine的大规模制备提供了新的思路。

Kifunensine is an alkaloid isolated from actinomycetes named Kitasatosporia kifunense. It is a neutral and stable compound,and an effective inhibitor of mannosidase I. Kifunensine is currently widely used in the field of drug discovery and has very high commercial value. However,the synthesis of Kifunensine is difficult,and there are problems such as low yield and high synthesis cost. In this paper,the cheap and easily available L-gulonic acid-γ-lactone was used as a raw material to obtain Kifunensine through a series of reactions. One-pot synthesis protocol has been applied in some of the synthetic steps,which makes the operation simple,and the total yield is 4. 8%. This novel method provides a probability to the large scale synthesis of Kifunensine.