Research in our lab seeks to bring the power of modern synthetic organic chemistry to bear on problems in biology and medicine. The main focus of our research involves synthesis of organic molecules that are biologically interesting. Subsequent mode of action studies of these molecules would provide opportunities for biological insights. Our research involves:
a) Natural product total synthesis: The rich structural diversity and complexity of natural products have inspired the imagination of chemists since the dawn of organic chemistry. Natural products have also been invaluable as tools for biological discoveries and as platforms for developing life-saving drugs. Our interest in natural product total synthesis also follows these two historic lines. Firstly, we are interested in using natural product total synthesis as the platform for measuring the limit of the state of the art of synthetic methods/strategies and as a source for inspiration of innovations to move beyond these boundaries. The synthesis will subsequently allow detailed mechanistic studies of the biological functions of relevant natural products and provide opportunities for biological discoveries.
b) Synthetic methodologies: Synthesis of complex molecular structures requires efficient chemical transformations. To this end, our lab is interested in the design and development of enantioselective organocatalytic reactions, transition metal-mediated transformations, and domino processes for rapid assembly of complex molecules.
c) Identification of small molecule probes for biological studies: Specific modulation of biological systems by small molecules has become a powerful method for biological studies. It complements genetic analysis by allowing access to novel and previously hindered biological space. In this research area, our lab is interested in identifying small molecule regulators of important biological processes by HTS (high-throughput screening) and rational design. These small molecules will be used as probes to help to define the molecular basis of the biological events.
Yang, J.; Shamji, A.; Matchacheep, S.; Schreiber, S. L. Identification of a small-molecule inhibitor of class Ia PI3Ks using cell-based screening. Chemistry & Biology 2007, 14, 371.
Paquette, L. A.; Peng, X.; Yang, J. Convergent enantioselective synthesis of the phytopathogen (+)-fomannosin. Agnew. Chem. Int. Ed. 2007, 46, 7817
Yang, J.; Long, O. Y.; Paquette, L. A. Concise total syntheses of the bioactive mesotricyclic diterpenoids jatrophatrione and citlalitrione. J. Am. Chem. Soc. 2003, 125, 1567.
Paquette, L. A.; Yang, J.; Long, O. Y. Concerning the antileukemic agent jatrophatrione: The first total synthesis of a [5.9.5] tricyclic diterpene. J. Am. Chem. Soc. 2002, 124, 6542.
Bernardelli, P; Moradei, O.M.; Friedrich, D.; Yang, J.; Gallou, F.; Dyck, B. P.; Doskotch, R. W.; Lange, T.; Paquette, L. A. Total asymmetric synthesis of the putative structure of the cytotoxic diterpenoid (-)-sclerophytin A and of the authentic natural sclerophytins A and B. J. Am. Chem. Soc. 2001, 123, 9021.
Paquette, L. A.; Gallou, F.; Zhao, Z.; Young, D. G.; Liu, J.; Yang, J.; Friedrich, D. Propensity of 4-methoxy-4-vinyl-2-cyclopentenones housed in tri- and tetracyclic frameworks for deep-seated photochemical rearrangement. J. Am. Chem. Soc. 2000, 122, 9610.