AbstractWe investigated the ability of several hydrolases to catalyze reactions with an abiotic water‐insoluble substrate, carbonic acid diphenyl ester, also known as diphenyl carbonate (DPC). In single‐phase water/organic systems, turnover numbers (TN) of greater than 2 × 104 min−1have been achieved for the hydrolysis of DPC. The Km values for the hydrolytic reaction were measured to be 200μM and 330μM for Candida cylindracea lipase and Porcine liver esterase, respectively. In addition to hydrolysis, we observed transesterification of carbonates with a wide variety of alcohol and phenol species. Transesterifications of DPC with bifunctional alcohols resulted in the synthesis of polycarbonates. We investigated the stability and transesterification activity of these enzymes in several water‐restricted environments to limit competing hydrolysis reactions. We find that, with the removal of water, hydrolysis is reduced more than four orders of magnitude while transesterification is diminished only 10‐fold (turnover numbers of 600 min−1 in water‐miscible systems to 60 min−1 in water‐restricted environments with pure Candida lipase). Stability of the Candida lipase in these water‐restricted environments (half‐life of longer than 3 days) is much greater than in water/organic single phase systems (5 h in 20% methanol). In addition, the Candida lipase displayed enantiomeric selectivity in transesterifications of DPC with racemic 2‐butanol (greater than 80% ee).