Lipase-catalyzed transformations as key-steps in the large-scale preparation of vitamins

In this account, scope and limitations for the application of hydrolytic enzymes (lipases) to large-scale syntheses of economically important bulk products (vitamins) are discussed. In three case studies, biocatalytic alternatives were compared to "classical" chemical processes. While in the first example (pantolactone) the lipase-catalyzed kinetic resolution by esterification of the hydroxy-gamma-lactone did not provide superior results for the overall-process, the synthetic strategies for the preparation of key-intermediates for fat-soluble vitamins could be improved significantly by using selected robust, immobilized lipases under optimized conditions. Regioselective mono-acetylation of a primary-secondary diol for a Vitamin A synthesis as well as mono-saponification of a hydroquinone-diacetate for a route to Vitamin E provided the monoacetylated key-intermediates in excellent yields and selectivities (generally >97%). Examples of laboratory procedures and continuous production on kilogram-scale are given. In consideration of environmental, technical, and economical aspects of modem industrial syntheses, these processes are, therefore, superior to classical (de)acetylation procedures. (C) 2002 Elsevier Science B.V. All rights reserved.