Development of a Practical Enzymatic Synthesis of Isosorbide-2-acetate

Using immobilized lipase, we developed an enzymatic synthesis of isosorbide-2-acetate (1), a key intermediate in the preparation of isosorbide-5-mononitrate. 1 was prepared in high yield (similar to 92%) with excellent regioselectivity (>99.5% d.e.) through hydrolysis (Novozym 435) or alcoholysis (lipase PS IM) of isosorbide-2,5-diacetate. The conditions for the enzymatic process were optimized. The substrate concentration could be 400-500 g/L, and the enzyme to substrate ratio was <10 wt %. The feasibility of enzyme recycling was also demonstrated. In addition, the enzymatic process was carried out on a kilogram scale and was proved to be scalable, efficient, and economical.