个人简介

BS Virginia Tech 2003 PhD California Institute of Technology (Stoltz) 2009 NIH Postdoctoral Fellow, Memorial Sloan-Kettering Cancer Center 2009-2012

研究领域

Synthesis of natural products/methodology development/synthesis and selective functionalization of peptides and proteins

Research in the Stockdill group will be focused on the design of elegant and efficient strategies for the synthesis of complex natural products and for the synthesis and manipulation of proteins and related structures. Through these efforts, we will explore chemical reactivity and develop new reaction methods. Target-Inspired Synthesis and Biological Studies of Natural Products Natural products have served as inspirational targets for synthetic chemists for decades, with structural challenges driving the development of novel methods for the construction of C-C, C-N, and C-O bonds. Meanwhile, they have also been the most consistently successful source of lead targets for pharmaceutical development over the last half-century. However, many promising targets are neglected due to their apparent complexity. Our research will focus on developing rapid, convergent, and innovative approaches to these challenging structures. Subsequently, the synthetic intermediates, targets, and analogs will be tested for novel biological activity. We will then embark on studies to determine the mechanism of action of these compounds in an effort to not only provide novel potential pharmaceuticals, but also to shed light on the biological pathways involved in particular disease states. Synthesis, Manipulation, and Biological Evaluation of Proteins and Mini-Proteins While small molecule natural products are advantageous drug targets, owing to their stability, relative accessibility, and rigidity, peptide and protein-derived treatments offer unique benefits including their high modularity, exquisite selectivity for their cellular targets, and generally favorable toxicity profiles. Our research in this area will begin by addressing serious challenges in the synthetic accessibility of these biomolecules, such as how to control the folding of synthetic proteins. We will also develop methods for the direct functionalization of peptides and proteins, which will enable cross-linking experiments, structure-function studies, and the interrogation of protein function. Finally, synthetic analogs of medically important proteins will be generated to modify their selectivity, stability and pharmacodynamics.

近期论文

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Wilson, R. M.; Stockdill, J. L.; Vadola, P. A.; Wu, X.; Li, X.; Danishefsky, S. J. A Fascinating Journey into History: Exploration of the World of Isonitriles as Precursors to Complex Amides. Angew. Chem. Int. Ed. 2012, 51, 2834.2348. Wu, X.; Stockdill, J. L.; Park, P. K.; Danishefsky, S. J. Expanding the Limits of Isonitrile-Mediated Amidations Through a Second -Generation Synthesis of Cyclosporine: On the Remarkable Stereosubtleties of Macrolactam Formation from Seco-Cyclosporins. J. Am. Chem. Soc. 2012, 134, 2378.2384. Wu, X.; Stockdill, J. L.; Wang, P.; Danishefsky, S. J. Total Synthesis of Cyclosporine: Access to N-Methylated Peptides via Isonitrile Coupling Reactions. J. Am. Chem. Soc. 2010, 132, 4098.4100. Stockdill, J. L.; Wu, X.; Danishefsky, S. J. Coupling of Hindered Alkyl Thioacids and Hindered Isonitriles: Mechanistic Studies. Tetrahedron Lett. 2009, 50, 5152.5155. Stockdill, J. L.; Behenna, D. C.; McClory, A. M.; Stoltz, B. M. An Efficient Synthesis of the Carbocyclic Core of Zoanthenol. Tetrahedron, 2009, 65, 6571.6575. Invited paper for Tetrahedron Prize Special Issue