Innovative Tools for Chemical Synthesis: Metal-Hydride Catalysis, Medicinal Motifs, and Molecular Probes

NIH RePORTER · NIH · R35 · $7,006 · view on reporter.nih.gov ↗

Abstract

Principle Investigator/Program Director (Last, first, middle): Dong, Vy, M Project Summary/Abstract Asymmetric transition metal catalysis has proven time and time again to be a crucial strategy in the pharmaceutical industry. The development of novel methods for accessing common organic scaffolds with improvements in the areas of atom-economy and selectivity has supported the mass production of valuable drug molecules. Hydroacylation is a powerful catalytic tool in which a hydrogen and an acyl group are added across a site of unsaturation via transition metal catalysis. This has the potential to be useful in the construction of carbonyl motifs for synthetic drug discovery. Azetidines are four-membered cyclic amines that can be found in drug candidates and natural products such as Nicotianamine and Ximelagatran. Our goal, described herein, is to explore the potential for a Rh-catalyzed asymmetric hydroacylation of azetines to generate novel azetidine scaffolds. Switching the ligand of choice, chiral Josiphos versus 1,2-bis(diphenylphosphino)ethane dppe, allows a regiodivergent strategy for the construction of chiral azetidines and achiral compounds. Building off of this work, we also aim to develop further hydroacylation methods to gain access to several other strained ring systems, which have been found to provide favorable structural and physicochemical properties necessary for molecular optimization in modern medicinal chemistry.

Key facts

NIH application ID
10974697
Project number
3R35GM127071-06S1
Recipient
UNIVERSITY OF CALIFORNIA-IRVINE
Principal Investigator
Vy M Dong
Activity code
R35
Funding institute
NIH
Fiscal year
2024
Award amount
$7,006
Award type
3
Project period
2018-05-01 → 2028-07-31