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.

The effect of an elastic functional group in a rigid binder framework of silicon-graphite composites on their electrochemical performance.

As a means of enhancing the electrochemical performance of silicon-graphite composites, we propose a novel binder candidate that is modified by a combination of rigid and elastic functional groups on its binder framework. To provide an efficient binder that is also capable of rapid volume changes, a co-polymer binder (PAA-PAA/PMA) is synthesized by employing poly(acrylic acid) (PAA) as the main binder framework and poly(acrylic acid)-co-poly(maleic acid) (PAA/PMA) as an additional elastic polymer auxiliary. This co-polymer binder (PAA-PAA/PMA) affords a good balance of adhesive and mechanical (rigidity and elasticity) properties, which creates an excellent cycle performance with a high specific capacity (751.1 mA h g(-1)) and considerable capacity retention (64.9%) after 300 cycles. This is attributed to the ability of the added elastic functional group to respond flexibly to volume changes, thereby enhancing the overall uniformity of the electrode and ensuring a consistent electronic network. On the basis of these findings, it is considered that embedding an elastic functional group into the binder framework is an effective approach to improve the overall performance of Si-graphite composite electrodes.

Asymmetric Synthesis of Functionalized trans-Cyclopropoxy Building Block for Grazoprevir.

A practical and asymmetric synthesis of a functionalized trans-cyclopropoxy building block for the preparation of the HCV NS3/4a protease inhibitor grazoprevir is reported. Intramolecular SN2 displacement-ring closure, followed by a Baeyer-Villiger oxidation, yields the desired trans-cyclopropanol with full control of diastereoselectivity. A terminal alkyne is then effectively installed using LiNH(CH2)2NEt2. Starting from (S)-epichlorohydrin, the cyclopropoxy building block is prepared in 51% overall yield with >99.8% optical purity without isolation of any intermediates.