Princeton Docket #
10-2624/2706-1
At the present time
there are few, if any, ways to incorporate halogen atoms selectively into
complex compounds. Halogenated organic compounds play a central role in organic
chemistry, affording important components of a variety of biologically active
molecules as well as pharmacologically active reagents. Alkyl chlorides also
find widespread use as intermediates in organic synthesis, as in cross coupling
reactions.
Based on research and
expertise in metalloporphyrin chemistry, researchers in the Department of
Chemistry, Princeton University have discovered a novel method for using
metalloporphyrins as effective catalysts for the incorporation of halogen atoms
such as chlorine, bromine and fluorine into a wide variety of compounds.
Utilizing inexpensive sodium hypochlorite as the chlorine source, a manganese
porphyrin mediated chemoselective and regioselective chlorination reaction has
been developed to achieve such halogenations. The development of
metalloporphyrin ¿catalyzed incorporation of halogen into unactivated
hydrocarbons could provide a significant new avenue for late stage drug
diversification. Further the realization of such a process could provide insight
into the mechanism of halogenations enzymes such as chloroperoxidase, a heme
containing chlorinating enzyme and Syr3, a non-heme Fe(II) α
¿ketoglutarate-dependent halogenase.
Advantages
- Clean, fast, and
inexpensive
- Easily scaled to
commercial use
Applications
- Drug
diversification
- Novel, small
molecule generation
- Generation of
biologically active molecules
Publications
Liu,W.; Groves, J.T.
¿ Manganese Prophyrins Catalyze Selective C-H Bond Halogenations¿, J. Am Chem.
Soc., 2010, 132, 12847-12849.
Intellectual Property
& Development Status
The reference cited
above describes several examples of using a manganese porphyrin mediated
aliphatic C-H bond chlorination using sodium hypochlorite as the chlorine
source, to produce alkyl chlorides as the major products with only trace amounts
of oxygenation products. Substrates with strong C-H bonds, such as neopentane
can also be chlorinated with moderate yield. Chlorination of a diagnostic
substrate, norcarene afforded rearranged products indicating a long-lived carbon
radical intermediate. Moreover, regioselective chlorination was achieved by
using a hindered catalyst. Patent protection is pending.
The Inventor
Professor John T
Groves, Professor of Chemistry
Professor Groves
major thrust of research is at the interface of organic, inorganic, and
biological chemistry. Many biochemical transformations as well as important
synthetic and industrial processes are catalyzed by metals. Current efforts
focus on the design of new, biomimetic catalysts and the molecular mechanisms of
these processes, the design and assembly of large scale membrane-protein-small
molecule constructs, studies of host-pathogen interactions related to iron
acquisition by small molecule siderophores and molecular probes of the role of
peroxynitrite in biological systems. Professor Groves is the recipient of many
accolades, including recent awards of the 2010 Hans Fischer Career Award in
Prophyrin Chemistry and the 2010 Remsen Award. He also was one of two people
selected to receive the 2008 Grand Prix de la Fondation de la Maison de la
Chimie, for his work with cytochrome P450 enzymes and model metalloporphyrin
catalysts.
Contact:
Laurie Tzodikov
Princeton University
Office of Technology Licensing ¿ (609) 258-7256¿ tzodikov@princeton.edu
PU
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