Beyond Chemoselectivity: Catalytic Site-Selective Aldolization of Diketones and Exploitation for Enantioselective Alzheimer Drug Candidate Synthesis
Date: Wednesday, April 12th, 2017
Time: 11:00 AM
Location: Building 4, Room 125
Dr. Thomas C. Nugent
Department of Life Sciences and Chemistry, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany
Site-selectivity, differentiating members of the same functional group type on one substrate, represents a forward-looking theme within chemistry: reduced dependence on protection/deprotection protocols for increased overall yield and step-efficiency. Despite these potential benefits and the expanded tactical advantages afforded to synthetic design, site-selectivity remains elusive and especially so for ketone-based substrates. Here we report on the site-selective intermolecular mono-aldolization of an array of prochiral 4-ketosubstituted cyclohexanones with concomitant regio-, diastereo-, and enantiocontrol. Importantly, the aldol products allow rapid access to molecularly complex keto-lactones or keto-1,3-diols respectively containing three and four stereogenic centers. The reaction conditions are of immediate practical value and general enough to be applicable to other reaction types. These findings are encapsulated by the first enantioselective formal synthesis of a leading Alzheimer research drug, a γ-secretase modulator (GSM), in the highest known yield.
He received his undergraduate and Ph.D. degrees from Virginia Tech in the state of Virginia (USA), and completed his Ph.D. degree in 1995 in natural product synthesis with Tomas Hudlicky. Tom's postdoctoral studies, 1996-1997, were completed in Liverpool (England) under Professor Stanley Roberts. There he made significant contributions to asymmetric epoxidation methodology using oligomeric amino acid based catalysts. From 1998 to 2003 he was a Process Research Chemist in San Francisco bay area. Because of mergers and acquisitions this meant he worked for several different companies (Catalytica, DSM, Pharmacia, and Pfizer Corporation). In 2004 he joined the faculty of Jacobs University Bremen as Assistant Professor and there he teaches a range of courses, e.g., from first year General Chemistry and Organic Chemistry to graduate level courses in Natural Product synthesis and another in Organocatalysis. His research interests initially focused on efficient synthetic pathways for accessing chiral amines, but for the last seven years he has devoted his research time to organocatalyzed reactions. The chemistry he develops is always within the context of identifying step-efficient methods for natural product or pharmaceutical drug syntheses. Today's presentation will give a feeling for both.
All faculty, researchers and graduate students are invited to attend.
There will be a get-together with refreshments at 10:45-11:00 a.m.