Regio- and stereoselective synthesis of chiral nitrilolactones using Baeyer–Villiger monooxygenases. Issue 46 (17th November 2016)

• Record Type: Journal Article
• Authors: Fink, Michael J.; Snajdrova, Radka; Winninger, Alexander; Mihovilovic, Marko D.
• Is Part Of: Tetrahedron. Volume 72:Issue 46(2016)
• Page Start: 7241
• Page End: 7248
• Publication Date: 2016-11-17
• Subjects: Biocatalysis -- BVMO -- Redox biotransformation -- Chiral building block -- Stereoelectronic effects; QGPJHEAJILPNLR-UHFFFAOYSA-N; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tet.2015.12.047
• Languages: English
• ISSNs: 0040-4020

Abstract

Abstract: This work describes the regio- and enantioselective synthesis of nitrile-containing chiral lactones from easily accessible ketone precursors using Baeyer–Villiger monooxygenases. These biocatalysts controlled the distribution of regioisomers much more tightly than commonly used stoichiometric reagents, additionally with good to excellent optical purity of products. A surprising case of strong stereoelectronic control was also observed. We tested a library of 14 catalysts using five-to eight-membered cyclic ketones with two different tether lengths to the nitrile group. In all but the largest series we found suitable wild-type enzymes for preparative scale synthesis of the target compounds. The diverse possibilities to further functionalize lactones and nitriles make this method interesting for the generation of chiral building blocks. Graphical abstract: