个人简介

B.Sc.(Fudan), M.A.(Columbia), Ph.D. 1991(Princeton)

研究领域

Organic chemistry, Chemical biology and biochemistry

Asymmetric catalysis and total synthesis of bioactive natural products; design, synthesis and biological applications of novel peptide mimics; chemical biology of natural products; fluorescent sensors for probing cellular processes. Research interests: synthetic organic chemistry, bioorganic chemistry, and chemical biology. 1. Oxidation Chemistry Dioxiranes are powerful oxidants for epoxidation, heteroatom oxidation and hydroxylation of C-H bonds. We developed a mild and general method for epoxidation of olefins using dioxiranes generated in situ from ketones and Oxone. We also developed chiral ketone catalysts for highly enantioselective epoxidation of unfunctionalized transolefins and trisubstituted olefins through steric and electronic tuning In addition, we discovered a novel method for selective oxidation of unactivated C-H bonds at d sites of ketones. Furthermore, we found that activated ketones and aldehydes could catalyze the decomposition of peroxynitrite (a potent oxidant generated in cells from nitric oxide and superoxide ion). The current focus is to develop highly specific and sensitive fluorescent probes for the detection of peroxynitrite and other reactive oxygen species in cells. 2. Aminoxy Acids as Building Blocks of Foldamers The search for peptidomimetics, which are structurally distinct from natural peptides yet able to function similarly to those peptides, is currently of great interest for medicinal chemistry. We discovered a new series of peptidomimetics based on aminoxy acids (a class of unnatural amino acids). Through computational and experimental studies, we showed that a-, b- and γ-aminoxy acids, when incorporated into peptides, could induce novel secondary structures such as turns and helices. In addition, these turns and helices are independent of side-chains. Therefore, they belong to the growing family of unnatural building blocks that give rigid and predictable secondary structures (so-called "foldamers"). As peptides containing aminoxy acids have excellent metabolic stability, aminoxy acids will be of tremendous potential in molecular design of peptide analogs for drug discovery. Recently we discovered a series of small molecules that self-assemble into ion channels for selective transport of cations or anions. The current focus is to explore the biomedical applications of those synthetic ion channels (such as chloride channels and potassium channels). 3. Catalytic Asymmetric Cyclization Reactions for Natural Product Synthesis Many natural products such as terpenoids and alkaloids with potent anti-inflammatory, anti-bacterial, and anti-tumor activities contain polycyclic structures. Considerable efforts have been directed at the development of efficient methods for selective ring construction. We discovered highly enantioselective atom and group transfer radical cyclization reactions catalyzed by chiral Lewis acids. In addition, we developed Pd(II)-catalyzed enantioselective oxidative tandem cyclization reactions. The current focus is to further explore new reactions for catalytic enantioselective ring construction and their applications in the asymmetric synthesis of bioactive natural products. 4. Chemistry and Biology of Triptolide Triptolide, a natural product isolated from Chinese medicinal herb Lei Gong Teng (Tripterygium wilfordii Hook F), has potent antitumor, anti-inflammatory, and immunosuppressive activities. We developed efficient and enantioselective syntheses of triptolide and its analogues, and identified structural features important for the biological activities. We are probing the interactions of triptolide with its cellular receptors, which will lead to better understanding of cell growth regulation and immune responses as well as discovery of new anticancer, anti-inflammatory, and immunosuppressive drugs.

近期论文

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D. Yang, Acc. Chem. Res., 2004, 37, 497-505. D. Yang, B.-F. Zheng, Q. Gao, S. Gu, N.-Y. Zhu. Angew. Chem., Int. Ed., 2006, 45, 255-258. D. Yang, H.-L. Wang, Z.- N. Sun, N.-W. Chung, J.- G. Shen. J. Am. Chem. Soc., 2006, 128, 6004-6005. K.-T. Yip, M. Yang, K.-L. Law, N.-Y. Zhu, D. Yang. J. Am. Chem. Soc., 2006, 128, 3130-3131. X. Li, B. Shen, X.-Q. Yao, D. Yang. J. Am. Chem. Soc. 2007, 129, 7264-7265. X. Li, Y.-D. Wu, D. Yang. Acc. Chem. Res. 2008, 41, 1428-1438. F. Chen, K.-S. Song, Y.-D. Wu, D. Yang. J. Am. Chem. Soc. 2008, 130, 743-755. X. Li, B. Shen, X.-Q. Yao, D. Yang. J. Am. Chem. Soc. 2009, 131, 13676-13680. R. Y. Kao, D. Yang, L.-S. Lau, W. H. W. Tsui, L.-H. Hu, J. Dai, M.-P. Chan, C.-M. Chan, P. Wang, B.-J. Zheng, J. Sun, J.-D. Huang, J. Madar, G.-H. Chen, H.-L. Chen, Y. Guan, K.-Y. Yuen. Nature Biotechnol. 2010, 28, 600-605. N. Ieda, H. Nakagawa, T. Peng, D. Yang, T. Suzuki, N. Miyata. J. Am. Chem. Soc. 2012, 134, 2563-2568.