CERC3-Sustainability - Liese-Haag-Griengl-Schwab: Sustainability by Advanced Chemoenzymatic Technologies /IV

Nature uses reaction sequences optimized over millions of years to produce stereoselective compounds in a highly sustainable way. The major aim of this project is to develop a multi-step reaction in a biomimetic way for the synthesis of products with a high enantio- and diastereoselectivity, starting from simple building blocks, such as an alken and a diene. As first step of the reaction sequence a homogeneously soluble macromolecular catalyst, a so- called `chemzyme`, is applied to catalyze the stereoselective Diels-Alder reaction. The chemzyme is necessary for this reaction because enzymatic Diels-Alder reactions are rare and have only recently been observed with a very limited substrate spectrum. A membrane, as in nature, retains this artificial catalyst. The organic product stream is passed on to a second reactor without further purification, where a stereoselective hydrocyanation is catalyzed by a hydroxynitrile lyase. Enzymes or chemzymes will catalyze a possible third transformation step leading to functionalized cyclohexenyl with chiral sidechains. This type of structure is difficult to access by other methods in a stereocontrolled fashion and will provide new chiral building blocks for application in drugs and agrochemicals These modification steps will also be integrated in the whole production process. This advanced chemoenzymatic technology enables the sustainable synthesis of a vast spectrum of highly diastereoselective products starting from simple materials like an alken and a diene. The multi-step synthesis will be carried out in a continuous flow reactor. By this setup the work-up protocols will be minimized. An overall sustainable synthesis is possible because of the integration of in situ product removal, recycling of the organic phase as well as recycling of the chemzymes and the enzymes. The efficient development of this advanced technology is assured by the expertise of the four research teams covering the areas of technical chemistry (team 1: Liese, Germany), polymer chemistry (team 2: Haag, Germany), bioorganic chemistry (team 3: Griengl, Austria), and molecular/structural biology (team 4: Schwab, Austria).

Nature uses reaction sequences optimized over millions of years to produce stereoselective compounds in a highly sustainable way. The major aim of this project is to develop a multi-step reaction in a biomimetic way for the synthesis of products with a high enantio- and diastereoselectivity, starting from simple building blocks, such as an alken and a diene. As first step of the reaction sequence a homogeneously soluble macromolecular catalyst, a so- called `chemzyme`, is applied to catalyze the stereoselective Diels-Alder reaction. The chemzyme is necessary for this reaction because enzymatic Diels-Alder reactions are rare and have only recently been observed with a very limited substrate spectrum. A membrane, as in nature, retains this artificial catalyst. The organic product stream is passed on to a second reactor without further purification, where a stereoselective hydrocyanation is catalyzed by a hydroxynitrile lyase. Enzymes or chemzymes will catalyze a possible third transformation step leading to functionalized cyclohexenyl with chiral sidechains. This type of structure is difficult to access by other methods in a stereocontrolled fashion and will provide new chiral building blocks for application in drugs and agrochemicals These modification steps will also be integrated in the whole production process. This advanced chemoenzymatic technology enables the sustainable synthesis of a vast spectrum of highly diastereoselective products starting from simple materials like an alken and a diene. The multi-step synthesis will be carried out in a continuous flow reactor. By this setup the work-up protocols will be minimized. An overall sustainable synthesis is possible because of the integration of in situ product removal, recycling of the organic phase as well as recycling of the chemzymes and the enzymes. The efficient development of this advanced technology is assured by the expertise of the four research teams covering the areas of technical chemistry (team 1: Liese, Germany), polymer chemistry (team 2: Haag, Germany), bioorganic chemistry (team 3: Griengl, Austria), and molecular/structural biology (team 4: Schwab, Austria).