Photon Equivalents as a Parameter for Scaling Photoredox Reactions in Flow: Translation of Photocatalytic C-N Cross-Coupling from Lab Scale to Multikilogram Scale.

With the development of new photocatalytic methods over recent decades, the translation of these chemical reactions to industrial-production scales using continuous-flow reactors has become a topic of increasing interest. In this context, we describe our studies toward elucidating an empirically derived parameter for scaling photocatalytic reactions in flow. By evaluating the performance of a photocatalytic C-N cross-coupling reaction across multiple reactor sizes and geometries, it was demonstrated that expressing product yield as a function of the absorbed photon equivalents provides a predictive, empirical scaling parameter.

A Next Generation Synthesis of BACE1 Inhibitor Verubecestat (MK-8931).

The development of a commercial manufacturing route to verubecestat (MK-8931) is described, highlights of which include the application of a continuous processing step to outcompete fast proton transfer in a Mannich-type ketimine addition, a copper-catalyzed amidation reaction, and an optimized guanidinylation procedure to form the key iminothiadiazine dioxide core.

Preclinical Experimental and Mathematical Approaches for Assessing Effective Doses of Inhaled Drugs, Using Mometasone to Support Human Dose Predictions.

Background: Understanding the relationship between dose, lung exposure, and drug efficacy continues to be a challenging aspect of inhaled drug development. An experimental inhalation platform was developed using mometasone furoate to link rodent lung exposure to its in vivo pharmacodynamic (PD) effects.

Methods: We assessed the effect of mometasone delivered directly to the lung in two different rodent PD models of lung inflammation.

Augmentation of postswelling surgical sealant potential of adhesive hydrogels.

Two-component hydrogels formed with star polyethylene glycol amine and linear dextran aldehyde polymers (PEG:dextran) show promise as tissue-specific surgical sealants. However, there is a significant loss of adhesion strength to soft tissues following PEG:dextran swelling, which may limit material ability to appose disjoined tissues and prevent leakage from surgical sites. We covalently incorporated the modified amino acid L-3,4-dihydroxyphenylalanine (L-DOPA) into PEG:dextran to enhance postswelling sealant performance.

STILLE CROSS-COUPLING REACTIONS OF ARYL MESYLATES AND TOSYLATES USING A BIARYLPHOSPHINE BASED CATALYST SYSTEM.

A catalyst system for the Stille cross-coupling reactions of aryl mesylates and tosylates is reported. Using the combination of Pd(OAc), XPhos, and CsF in -BuOH an array of aryl and heteroaryl sulfonates were successfully employed in these reactions. Morever, heteroarylstannanes, such as furyl, thiophenyl, and -methylpyrrole, which are often prone to decomposition, were efficiently coupled under these conditions.