工作经历 |
2019-present, Professor & Doctoral Supervisor, School of Pharmaceutical Sciences, Jilin University 2019-present, Director, The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, P. R. China 2017-2019, Visiting Scholar, Scripps Research, USA (Advisor: Prof. Phil S. Baran) 2016-2019, Associate Professor & Doctoral Supervisor, School of Pharmaceutical Sciences, Jilin University 2011-2016, Associate Professor & Master Supervisor, School of Pharmaceutical Sciences, Jilin University 2008-2011, Lecturer, School of Pharmaceutical Sciences, Jilin University |
研究领域 |
Major: Medicinal chemistry Research Fields: The development of new methods for drug synthesis and design Research Interests: Organic electrosynthesis, drug discovery and chemical biology Academic achievement: High-throughput screening (HTS) of chemical libraries has become an important approach for the discovery of tool compounds and drug leads. However, this method requires robotics and other sophisticated equipment to increase the scale and speed of assays. An efficient strategy for the discovery of biologically active compounds by combining diversity-oriented synthesis and converging screening was realized in our group. We have developed several new synthetic methods via iminium ion intermediates to prepare libraries of novel heterocyclic scaffolds based on privileged structures. With the iterative screening strategy, we identified novel pyrido[2,3-b][1,4]benzothiazepines showing potent inhibitory activity against paclitaxel-resistant cell line H460TaxR, which exhibits much less toxicity toward normal human fibroblasts. A series of novel pyrimido[4,5-b][1,4]benzothiazepines with potent inhibitory activity against p38α kinase in vitro and in cellular assays were discovered by a two-round screening process. A series of pyrimidine hydroxamic acids were found to be effective in causing apoptosis in RPMI 8226 cells and exhibited promising HDAC-inhibitory activities. This strategy was selected for inclusion in the ACS virtual issue (Techological Advances in Medicinal Chemistry). Organic electrosynthesis, which achieves redox reactions with traceless electric current, is accepted to be an environmentally friendly and enabling synthetic tool. Hindered ethers are of high value for various applications; however, they remain an underexplored area of chemical space because they are difficult to synthesize via conventional reactions. Such motifs are highly coveted in medicinal chemistry, because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. A simple route towards the synthesis of hindered ethers was realized, in which electrochemical oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochemical potentials, capture an alcohol donor under nonacidic conditions; this enables the formation of a range of ethers that would otherwise be difficult to access. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chemical scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labour required to prepare them. This work was highlighted by C&EN, Synfact, ScienceDaily, and ChemistryViews etc. |
科研成果 |
Based on the interesting and important results, I have published over 30 scientific articles, including Nature, as the first author or corresponding author, and I am also a co-inventor of 3 issued patents. I have led 12 research projects including National Natural Science Foundation of China, and was elected as a member of the Medicinal Chemistry of Jilin Pharmaceutical Society. Selected publications： 1. Xiang, Jinbao#; Shang, Ming#; Kawamata, Yu; Lundberg, Helena; Reisberg, Solomon H; Chen, Miao; Mykhailiuk, Pavel; Beutner, Gregory; Collins, Michael R; Davies, Alyn; Del Bel, Matthew; Gallego, Gary M; Spangler, Jillian E; Starr, Jeremy; Yang, Shouliang; Blackmond, Donna G; Baran, Phil S*; Hindered Dialkyl Ether Synthesis with Electrogenerated Carbocations, Nature, 2019, 573(7774): 398–402. 2. Bai, Ya; Shi, Lingling; Zheng, Lianyou; Ning, Shulin; Che, Xin; Zhang, Zhuoqi; Xiang, Jinbao*; Electroselective and Controlled Reduction of Cyclic Imides to Hydroxylactams and Lactams, Organic Letters, 2021, 23(6), 2298–2302. 3. Bai, Ya#; Liu, Nian#; Wang, Shutao; Wang, Siyu; Ning, Shulin; Shi, Lingling; Cui, Lili*; Zhang, Zhuoqi; Xiang, Jinbao*; Nickel-Catalyzed Electrochemical Phosphorylation of Aryl Bromides, Organic Letters, 2019, 21(17): 6835–6838. 4. Xiang, Jinbao; Zhang, Zhuoqi; Fu, Renzhong; Ternansky, Robert J.; Gladstone, Patricia L.; Allan, Amy L.; Donate, Fernando; Parry, Graham; Juarez, Jose; Mazar, Andrew P.; Bai Xu*; The Discovery of Kinase Inhibitors by a Combination of Diversity-Oriented Synthesis and Selective Screening, MedChemComm, 2016, 7(10), 1946–1951. 5. Xiang, Jinbao; Zhang, Zhuoqi.; Mu, Yan; Xu, Xianxiu; Guo, Sigen; Liu, Yongjin; Russo, Daniel P.; Zhu, Hao; Yan, Bing*; Bai, Xu*; Discovery of Novel Tricyclic Thiazepine Derivatives as Anti-Drug-Resistant Cancer Agents by Combining Diversity-Oriented Synthesis and Converging Screening Approach, ACS Combinatorial Science, 2016, 18(5), 230–235. |
