Reaction Engineering for Consecutive Enzymatic Reactions in Peptide Synthesis: Application to the Synthesis of a Pentapeptide

A single‐pot enzymatic synthesis of Z‐CCK5 (4–8) is presented in this work, employing Z‐Gly‐Trp‐OBzl as acyl donor, under kinetic control. The first goal of the work is the development of a synthetic strategy allowing the use of the same medium for two reactions catalyzed by immobilized α‐chymotrypsin, discriminating between simultaneous and consecutive addition systems. The second goal is the maximization of the pentapeptide yield as a function of the molar excess of both nucleophiles employed. A maximum yield of 36% was obtained, and the addition strategy as well as the optimal initial concentrations of substrates have been determined.