(648d) Continuous Purification of Artemisinin and Artesunate

Andreas Seidel Morgenstern,^1,2 Ju Weon Lee,¹ Zoltan Horvath,¹ Elena Horosanskaia,¹

Heike Lorenz,¹ Kerry Gilmore,³ Daniel Kopetzki,³ D. Tyler McQuade,³ Peter H. Seeberger^3,4

1) Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany

2) Otto-von-Guericke-University, Chair for Chemical Process Technology, Universitaetsplatz 2, 39106 Magdeburg, Germany

3) Max-Planck-Institute of Colloids and Interfaces, Department of Biomolecular Systems, Am Mühlenberg 1, 14476 Potsdam, Germany

4) Freie Universität Berlin, Institute of Chemistry and Biochemistry, Arnimallee 22, 14195 Berlin

Germany

Artemisinin, contained in sweet wormwood, and its derivatives β-artemether, β-arteether and α-artesunate are currently the basis for the most effective ways to cure the malaria disease [1]. Continuous photocatalytical synthesis of artemisisin from the waste product dihydroartemisinic acid was recently reported to be capable to produce in a laboratory flow reactor up to 3.5 kg/L/day with approx. 70 wt. % yield [2, 3]. The possibility of further synthesizing the mentioned derivatives in a continuous way could be demonstrated just recently for artesunate [4].

For a model target compound it was shown, that the outlet of a continuously operated flow reactor could be successfully fed directly into a simulated moving bed (SMB) chromatography unit in order to carry out both processes continuously [5, 6].

We will present results for various scenarios of the continuous isolation of artemisinin and artesunate from the effluent of continuously operated reactors. One of the investigated options is based on applying a 3-zone open-loop SMB process with an additional regeneration zone. The potential of combinations of chromatography and crystallization processes [7, 8] will be also discussed.

References

[1] World Malaria Report, World Health Organization, Geneva, 2011.

[2] F. Lévesque, P.H. Seeberger,

     Angew. Chem. Int. Ed., 2012, 51, 1706 – 1709.

[3] D. Kopetzki, F. Lévesque, P.H. Seeberger,

     Chem. Eur. J., 2013, 19, 5450 – 5456.

[4] K. Gilmore, D. Kopetzki, J.W. Lee, Z. Horvath, D. T. McQuade, A. Seidel-Morgenstern,

     P.H. Seeberger, manuscript submitted

[5] A.G. O’Brien, Z. Horváth, F. Lévesque, J.W. Lee, A. Seidel-Morgenstern, P.H. Seeberger,

      Angew. Chem. Int. Ed., 2012, 51, 7028 – 7030.

[6] J. W. Lee, Z. Horváth, A.G. O’Brien, P.H. Seeberger, A. Seidel-Morgenstern,

      Chem. Eng. J., 2014, in print

[7] E. Horosanskaia, A. Seidel-Morgenstern, H. Lorenz,

     Themochimica Acta, 2014, 578, 74 - 81.

[8] H. Lorenz, A. Seidel-Morgenstern,

     Angew. Chem. Int. Ed., 2014, 53, 1218 – 1250.