Wednesday, February 7, 2018
3:00 pm
Noyes 153 (J. Holmes Sturdivant Lecture Hall)

Organic Chemistry Seminar

Eric Ashley, Ph.D.; Danielle Schultz, Ph.D.; Christopher Sinz, Ph.D. , Merck

3:00 pm     Dr. Eric Ashley, Merck     "Dynamic Stereocontrol in Drug Discovery and Development"

Enantioenriched chiral molecules are ubiquitous in drug discovery and pharmaceutical development.  The efficient synthesis of such compounds is routinely complicated by the correlation of stereocenters to stereodefining chemical transformations, almost always in a 1:1 ratio.  Dynamic asymmetric processes allow for an escape from this paradigm.  Investigations toward the syntheses of Vernakalant and the GPR40 AgoPAM chromans have led to the discovery of new dynamic kinetic transamination and chroman reduction reactions.  The discovery and development of these transformations and their application to the synthesis of the inspiring compounds will be discussed.

3:40 pm     Dr. Danielle Schultz, Merck     "Oxyfunctionalization fo Remote C-H Bonds of Aliphatic Amines via Decatungstate Photocatalysis"

Derivatized aliphatic amines represent a common and important class of chemical building blocks prevalent in the pharmaceutical, agrochemical and material industry. As a result, approaches to directly install functionality on simple and unbiased amine precursors remain of paramount importance.  While functionalizing alpha to the nitrogen has been well-studied and numerous methods exist, achieving remote amine functionalization remains largely underdeveloped. Consequently, we reasoned that a direct and protecting group free oxygenation of aliphatic amines (to arrive at keto-amine products) would provide an ideal means for introducing diverse functionality. Through the use of high throughput experimentation (HTE) a photochemical oxidation was identified that relied upon hydrogen peroxide (or oxygen) as the oxidant in combination with a non-precious metal photocatalyst. These conditions were shown to selectively oxidize a series of diverse aliphatic amine starting materials to their remotely oxidized analogs and was amenable to scale-up in  flow.

4:20 pm     Dr. Christopher Sinz, Merck     "Studies in Neuroscience Drug Discovery"

Alzheimer's disease (AD) is a critical unmet medical need.  This presentation will cover medicinal chemistry efforts spanning lead identification through lead optimization for a novel target for the symptomatic treatment of AD.  In addition, we will describe the in vivo pharmacology of the lead compounds along with the discovery of a novel small molecule imaging tool (PET tracer) to guide clinical development. 

Contact Victoria Brennan vicky@caltech.edu at 6151
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