New production route for hydrazines
Optically active hydrazine compounds are valuable intermediate compounds for the synthesis of several pharmaceuticals and precursors for natural products. A prominent example is D-(+)-1-Phenyl-2-hydrazinopropan (D-(+)-JB-516), which includes a chiral hydrazine and acts as inhibitor of monoaminooxidase in mice brain. A precursor towards synthesis of the natural compound Manzacidin C also contains a chiral hydrazine as structural motif.
So far, hydrazines are prepared usually via traditional chemical synthesis methods. But these methods have several disadvantages, like the risk of generating hydrogen cyanide in an acidic environment as well as only low product yields. Alternative reaction modes using triethylsilane need relatively harsh reaction conditions and long reaction times.
A special focus in this invention is on the enantioselective synthesis of chiral hydrazines.
A new route is now described here with the usage of an imine reductase for the reduction of the C=N-double bond of hydrazones (I) to the corresponding hydrazines (II). Especially, in the present innovation, it was shown that imine reductases are valuable biocatalysts for the enantioselective reduction of hydrazones and may therefore be used for synthesis of enantiomeric enriched or pure products (up to 99%).
In an improved method, S- and R-selective enzymes may be used to fabricate the product of need.
- New method for the synthesis of hydrazines
- Production of enantiomeric enriched or pure products possible (99%)
- Reduction of hazardness in the preparation of hydrazines
- Smooth reaction conditions of the process running at ambient temperature
- Avoidance of toxic and expensive heavy metal catalysts
PROvendis is offering licenses for the invention to interested companies on behalf of the University of Bielefeld. There is also the possibility of collaboration with the inventors.
In case of interest we are pleased to inform you about the current patent status. A first search report of the German Patent Office shows good patentability.
Gröger, H. (2018) Enzyme catalysis in the synthesis of pharmaceuticals. Bioorganic & Medicinal Chemistry 26, 7, 1239-40