One-Flow

ONE-FLOW Research Project: Catalyst Cascade Reactions in ‘One-Flow’ within a Compartmentalized, Green-Solvent ‘Digital Synthesis Machinery’ – End-to-End Green Process Design for Pharmaceuticals. Subject area
Continuous synthesis Keywords
continuous flow, active pharmaceutical ingredients, catalysis, cascade reactions Staff
Ass.Prof. Priv.-Doz. Dipl.-Ing. Dr.techn. Heidrun Gruber-Wölfler
Katharina Hiebler BSc MSc
Bianca Grabner BSc Dipl.-Ing.
Manuel Maier BSc Dipl.-Ing. Duration
01. January 2017 – 31. December 2020

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Multistep synthesis with ‘horizontal hierarchy’

Description

The aim of the ONE-FLOW Project is the translation of ‘vertical hierarchy’ of chemical multistep synthesis into ‘horizontal hierarchy’. This means, that the single steps of a reaction cascade are not performed in a consecutive fashion in confined compartments but different chemo- and biocatalysts work together in one compartment, in this way achieving multiple reactions in one step. Within the framework of the project, TU Graz is responsible for the development of the integrated multistep synthesis of valsartan and sacubitril in continuous flow. The compounds are well known as APIs in a combination drug for the treatment of hypertension and chronic heart failure (Entresto®, Novartis). The key step of both processes is a Suzuki-Miyaura cross-coupling reaction, facilitated by in-house developed heterogeneous Pd-catalysts with the molecular formula Ce_0.99−xSn_xPd_0.01O_2−δ. Furthermore, the use of immobilized enzymes is planned to accomplish formation of the final products. Required compartmentalization is intended to be achieved by so-called Pickering emulsions of oil and water phases. Sponsored by: H2020-FETOPEN-2016-2017 programme of the European Commission (Grant agreement number: 737266-ONE FLOW).

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Project Leader

Heidrun Gruber-Wölfler
Assoc.Prof. Dipl.-Ing. Dr.techn.

Phone: +43 316 873 - 30406

woelfler@tugraz.at

Project Publications

Hiebler, K., Gruber-Woelfler, H. et. al. (2018) Beilstein Journal of Organic Chemistry, 14, 648–658.