Mary Watson
University of Delaware, DE·Chemistry
Most medicines are built from carbon frameworks that must be assembled in a precise three-dimensional shape, because mirror-image versions of the same molecule can behave very differently in the body. Two long-running projects develop catalytic reactions that build such carbon frameworks from cheap, abundant starting materials, with control over that three-dimensional shape; a third project builds shared instrumentation that supports biomedical research at the University of Delaware.
- Fields
Chemistry
Biochemistry
Biomedical Engineering
- Topics
enantioselective catalysis
asymmetric synthesis
cross-coupling
- Grants
- 3 known grants, through Feb 2030
What they work on
- Develop enantioselective copper-catalyzed additions of alkynes to cyclic oxocarbenium and iminium ions, positively charged ring intermediates, to make oxygen and nitrogen heterocycles with tri- and tetrasubstituted stereocenters next to the heteroatom.
- Establish enantioselective difunctionalization reactions that install two groups at once on simple achiral starting materials, delivering the disubstituted heterocycles common in bioactive compounds.
- Convert heterocyclic alkynylation products into acyclic amines bearing tetrasubstituted stereocenters, or elaborate them into natural products and natural product analogues.
- Develop stereospecific cross-couplings of tertiary benzylic alcohol derivatives, which are available in high enantiomeric excess, to build all-carbon quaternary and other fully substituted stereocenters in high enantiopurity.
- Extend deaminative cross-coupling of primary alkyl amines activated as Katritzky pyridinium salts under nickel catalysis, and use mechanistic studies to understand and optimize the challenging catalytic steps.
- Build and support the Multiscale Biomolecular Sensing Research Core, including high-throughput chromatography, biophysical instrumentation, a CRISPR/Cas9 transgenic mouse subcore and an expanded computational cluster.
More about the research
One project develops enantioselective, copper-catalyzed additions of alkynes, carbon–carbon triple bonds, to reactive positively charged intermediates called cyclic oxocarbenium and iminium ions. The products are oxygen- and nitrogen-containing rings (heterocycles) bearing three- or four-substituted stereocenters next to the ring's oxygen or nitrogen atom, motifs that are common in bioactive molecules but hard to make as single mirror images. Because disubstituted heterocycles are so prevalent in bioactive compounds, the group is establishing enantioselective difunctionalization reactions that add two groups at once, raising the complexity of simple, non-chiral starting materials in one step. Alkynylation of a range of cationic intermediates is being explored to reach diverse heterocycles, which can be opened into valuable acyclic amines with fully substituted stereocenters or elaborated toward natural products and their analogues. Students on this project are trained in chemical synthesis and enantioselective catalysis, and the grant describes outreach at the University-associated daycare that introduces preschool through third-grade children to science.
Why it matters
Drug candidates with saturated carbon atoms and three-dimensional shape are more likely to progress toward medicines, yet such structures are difficult to prepare as single mirror images. New catalytic methods that build them from readily available alcohols and amines could broaden the molecules available to medicinal chemists. The shared Research Core would add chromatography, biophysics, transgenic mouse and computing capabilities for biomedical research across Delaware.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Gregory Fu
California Institute of Technology, CA·Chemistry
Develop nickel- and copper-catalyzed substitution reactions that couple families of alkyl electrophiles and nucleophiles not previously shown to react together, including highly hindered substrates.
Mark Biscoe
CUNY City College, NY·Chemistry
Develop palladium- and copper-catalyzed cross-coupling reactions that transfer handedness from enantioenriched secondary alkylboron reagents to new carbon centers with predictable retention or inversion.
Brian Stoltz
California Institute of Technology, CA·Chemistry
Develop new stereoselective reactions that produce densely substituted, enantioenriched building blocks for synthesizing complex molecules.
The school
University of Delaware: 22 labs on PI Pages, $466M a year on research, 298 research doctorates a year.
Reach out
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