Birgit Kosjek

Resolution of 2,2-Disubstituted Epoxides via Biocatalytic Azidolysis

A practical procedure for the enzymatic resolution of 2-alkyl-2-aryl-disubstituted epoxides using the Codex HHDH P2E2 enzyme and sodium azide is reported. This method allowed the synthesis of novel regio- and enantioselective 1-azido-2-arylpropan-2-ols in excellent yields. Furthermore, these intermediates were used for the preparation of enantiomerically enriched amino alcohols and aziridines containing a tertiary center.

Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases

In this manuscript we wish to report the discovery of MK-7246 (4), a potent and selective CRTH2 (DP2) antagonist. SAR studies leading to MK-7246 along with two synthetic sequences enabling the preparation of this novel class of CRTH2 antagonist are reported. Finally, the pharmacokinetic and metabolic profile of MK-7246 is disclosed.

Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High pH Dynamic Kinetic Reduction

Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high-pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding.