Expanding the Chemical Diversity in Artificial Imine Reductases Based on the Biotin–Streptavidin Technology. Issue 4 (16th January 2014)

• Record Type: Journal Article
• Authors: Quinto, Tommaso; Schwizer, Fabian; Zimbron, Jeremy M.; Morina, Albert; Köhler, Valentin; Ward, Thomas R.
• Is Part Of: ChemCatChem. Volume 6:Issue 4(2014:Apr.)
• Page Start: 1010
• Page End: 1014
• Publication Date: 2014-01-16
• Subjects: asymmetric catalysis -- biotin–streptavidin technology -- imine reduction -- metalloenzymes -- transfer hydrogenation; Catalysis -- Periodicals; 541.39505
• DOI: 10.1002/cctc.201300825
• Languages: English
• ISSNs: 1867-3880

Abstract

Abstract: We report on the optimization of an artificial imine reductase based on the biotin‐streptavidin technology. With the aim of rapidly generating chemical diversity, a novel strategy for the formation and evaluation of biotinylated complexes is disclosed. Tethering the biotin‐anchor to the Cp* moiety leaves three free coordination sites on a d 6 metal for the introduction of chemical diversity by coordination of a variety of ligands. To test the concept, 34 bidentate ligands were screened and a selection of the 6 best was tested in the presence of 21 streptavidin (Sav) isoforms for the asymmetric imine reduction by the resulting three legged piano stool complexes. Enantiopure α‐amino amides were identified as promising bidentate ligands: up to 63 % ee and 190 turnovers were obtained in the formation of 1‐phenyl‐1, 2, 3, 4‐tetrahydroisoquinoline with [IrCp* biotin (L ‐ThrNH2 )Cl]⊂SavWT as a catalyst. Abstract : Biotinspired! A new strategy for the generation of chemical diversity in artificial transfer hydrogenases (ATHases) based on the biotin–streptavidin technology is disclosed. By combining a biotinylated MCp* fragment with 34 commercially available ligands in the presence of wild‐type streptavidin, promising candidates for the asymmetric reduction of imines are identified. Selected ligands are screened against 21 streptavidin isoforms and the performance of the resulting constructs is evaluated.