Hydrolytic enzymatic transformation of advanced synthetic intermediates: on the choice of the organic cosolvent

For enzymatic hydrolyses of advanced synthetic intermediates, the use of an organic cosolvent is often warranted. As a model study, the cosolvent dependence (at 10 volume%) of the key enzymatic step in our asymmetric synthesis of (-)-podophyllotoxin was examined. At high protein concentrations and rt, DMSO and the polyethereal organic cosolvents dioxane, diglyme and triglyme emerged as the best organic cosolvents, in terms of yield, % ee and catalytic efficiency (V(max)/K(m)). However, only in 10% triglyme was optimal efficiency maintained at both lower protein concentration and higher temperature. (C) 1999 Elsevier Science Ltd. All rights reserved.