The construction of pharmaceutical and bioactive molecules relies on methods for the formation of carbon-carbon bonds. Over the past decade olefin metathesis has emerged as a powerful means by which to form these bonds in applications ranging from, but not limited to, small organic molecules, complex natural products, and well-controlled polymer architectures. The availability of robust catalysts that are highly active, efficient, stable, and selective is key to the further development of these wide-ranging applications. Over the last granting period catalysts were prepared that facilitate metathesis (a) in aqueous solutions, (b) with sterically hindered substrates, (c) at lower catalyst loadings, and (d) with higher levels of enantioselectivity. A powerfully simple method for the construction of N-heterocyclic carbene ligands was developed. This method will be exploited over the next granting period for the development of stereoselective metathesis catalysts (controlling the trans:cis ratio of the carbon-carbon double bonds), and improvement of catalyst stability (to lower catalyst loadings), among other proposed improvements. The design and preparation of such catalysts would further enable the rapid and selective formation of biologically-relevant chemical compounds.

Public Health Relevance

The preparation of bioactive molecules remains a significant challenge in the study of human health and related fields. Olefin metathesis is now routinely used for the constructions of such molecules. Development of catalysts for this reaction is key to the advancement of this powerful carbon-carbon bond forming technology.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Synthetic and Biological Chemistry B Study Section (SBCB)
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Lees, Robert G
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California Institute of Technology
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