(83w) Optimizing the Deprotection of the Amine Protecting P-Methoxyphenyl (PMP) Group in An Automated Microreactor Platform

We have previously shown that small microreactors with volumes in the range of a few microliters can be successfully applied to screen and optimize biosynthesis reactions consuming only minute amounts of reaction fluids[1,2]. Although our in-house developed microreactor platform is capable of producing such a large amount of data points in a single day, the generation of the amount of data required for optimizing three or more parameters would be very time-consuming if all possible reaction conditions would be screened in a grid with regular intervals. Therefore we applied the principles of Design of Experiments (DOE), more specifically D-optimal design[3] to optimize an industrially relevant reaction: the removal of a p-methoxyphenyl (PMP)[3] amine-protecting group. The applied DOE resulted in a very efficient screening of this reaction. It could be concluded that the PMP group could readily be removed within five minutes using the optimal reaction conditions. These optimal conditions were also applied to synthesize gram quantities of the deprotected amine in the continuous flow reactor.

[1] K. Koch, R.J.F. van den Berg, P.J. Nieuwland, R. Wijtmans, H.E. Schoemaker, J.C.M. van Hest, F.P.J.T. Rutjes, Biotechnol. Bioeng, in press.

[2] P.J. Nieuwland, K. Koch, J.C.M. van Hest and F.P.J.T. Rutjes, Proceedings of µTAS 2006 Conference, Tokyo, 2006, 870-872.

[3] P. F. de Aguiar, B. Bourguignon et al., Chemom. Intell. Lab. Syst., 1995, 199-210.

[4] J.M.M. Verkade, L.J.C. van Hemert, P.J.L.M. Quaedflieg, P.L. Alsters, F.L. van Delft, F.P.J.T. Rutjes, Tetrahedron Let., 2006, 8109-8113.