Two-step enzymatic selective synthesis of water-soluble ketoprofen-saccharide conjugates in organic media.

ABSTRACT

Ketoprofen-saccharide conjugates were synthesized by selectively enzymatic hydrolysis and acylation. Firstly, the (S)-ketoprofen vinyl ester was prepared by enzymatic hydrolysis of (R,S)-ketoprofen vinyl ester. Then enzymatic transesterification of (S)-ketoprofen vinyl ester with a series of saccharides were performed by the catalysis of a commercial protease from Bacillus licheniformis (BLP) in organic medium mixture of pyridine and tert-butanol. The ketoprofen was selectively conjugated onto the primary hydroxyl group of saccharides and with high yield after 72h. Partition coefficient determination showed that all the products have better water solubility than parent ketoprofen. Chemical hydrolysis experiment indicated that 50% ketoprofen could be release from ketoprofen glucoside and maltoside in aqueous buffer (pH 7.4) within 48h.