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A Quest for Mechanistic Insight into Biocatalytic Aerobic Oxidations

Date: 
Tuesday, September 25, 2018 - 12:45 to 14:00
Speaker: 
Shane Grosser
Affiliation: 
Department of Chemical Engineering Research and Development, Merck Research Laboratories
Event Category: 
LMC - Lectures in Modern Chemistry
Location: 
Chemistry B250

Abstract:

Since 2014, the Process Development Intensification Laboratory (iLab) within Chemical Engineering R&D at Merck has been focused on the development and democratization of tools and techniques to enable acquisition of deeper, more fundamental process understanding in a resource sparing manner. This is predominantly centered around the concept of data intensification, specifically around enabling more efficient data capture, data reduction and data analysis. This talk will showcase how collaborative efforts across process chemistry, process engineering, biocatalysis and analytical chemistry are contributing towards building mechanistic understanding of a novel biocatalytic aerobic oxidation. Generally speaking, the oxidation of alcohols to aldehydes represents key transformations in organic synthesis and traditionally, many of these oxidation reactions have been carried out using stoichiometric amounts of transition metal based oxidants. Here, we will discuss the enzymatic desymmetrization of 2-ethynylglycerol in support of MK-8591; a nucleoside reverse transcriptase inhibitor (NRTI) currently progressing through Phase II clinical trials, displaying high promise as a next-generation anti-HIV drug. To accomplish this goal, the Merck has recently expanded its biocatalytic platform to include the copper-dependent galactose oxidases (GOases) which are highly efficient enzymes for the mild, regio- and stereoselective oxidation of a broad variety of primary and secondary alcohols, polyols and sugars. These enzyme are capable of catalytic oxidations in water, making direct use of the molecular oxygen of the air. Furthermore, this talk will highlight past and ongoing efforts, centering on enzyme discovery and reaction engineering, underpinned by data-rich experimentation methods including; high-throughput experimentation and analysis, automation, and insitu reaction analysis using novel analytical tools.