Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

János Máté Orosz; Dóra Ujj; Petr Kasal; Gábor Benkovics; Erika Bálint

doi:10.3762/bjoc.19.25

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

Beilstein J Org Chem. 2023 Mar 9:19:294-302. doi: 10.3762/bjoc.19.25. eCollection 2023.

Authors

János Máté Orosz¹, Dóra Ujj¹, Petr Kasal², Gábor Benkovics¹, Erika Bálint¹

Affiliations

¹ Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
² Department of Organic Chemistry, Faculty of Science, Charles University, 128 43 Prague 2, Czech Republic.

Abstract

The first continuous flow method was developed for the synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin starting from native β-cyclodextrin through three reaction steps, such as monotosylation, azidation and reduction. All reaction steps were studied separately and optimized under continuous flow conditions. After the optimization, the reaction steps were coupled in a semi-continuous flow system, since a solvent exchange had to be performed after the tosylation. However, the azidation and the reduction steps were compatible to be coupled in one flow system obtaining 6-monoamino-6-monodeoxy-β-cyclodextrin in a high yield. Our flow method developed is safer and faster than the batch approaches.

Keywords: 6-monoamino-6-monodeoxy-β-cyclodextrin; H-cube; azidation; continuous flow; monosubstitution; reduction; β-cyclodextrin.

Grants and funding

This research was funded by the Hungarian Research Development and Innovation Office (FK142712) and by the Cylolab Grant. This work was performed in the frame of the Pharmaceutical Research and Development Laboratory project (PharmaLab, RRF-2.3.1-21-2022-00015), implemented with the support provided from the Széchenyi Plan Plus, financed under the National Laboratory Program funding scheme.