齐湘兵

高级研究员，化学中心主任，清华大学生物医学交叉研究院副教授

Xiangbing Qi, Ph.D.

Associate Professor, TIMBR, Associate Investigator and Director of Chemistry Center, NIBS, Beijing, China

教育经历 Education

2005-2009年 美国德州大学西南医学中心生物化学系，有机化学博士

Ph.D. Organic Chemistry，Department of Biochemistry，University of Texas Southwestern Medical Center at Dallas

2001-2004年 同济大学有机化学硕士

M.S. Organic Chemistry, Department of Chemistry, Tongji University

1997-2001年 济南大学应用化学学士

B.S. Applied Chemistry, School of Chemistry and Chemical Engineering, University of Jinan

工作经历 Professional Experience

2021年- 清华大学生物医学交叉研究院副教授，北京生命科学研究所高级研究员

Associate Professor, TIMBR, Associate Investigator, National Institute of Biological Sciences, Beijing, China

2013年- 北京生命科学研究所化学中心主任

Director of Chemistry Center, National Institute of Biological Sciences, Beijing, China

2010-2013年 美国德州大学西南医学中心，有机化学与药物化学博士后

Postdoctoral Fellow, Organic Chemistry and Medicinal Chemistry, Department of Biochemistry，University of Texas Southwestern Medical Center at Dallas.

2009-2010年 美国伊利诺伊大学厄巴纳-香槟分校，有机化学博士后

Postdoctoral Fellow, Organic Chemistry，Department of Chemistry，University of Illinois at Urbana-Champaign.

2004-2005年 中科院上海有机所，有机合成/药物研发研究助理

Research Assistant, Organic synthesis/Medicinal chemistry，Shanghai Institute of Organic Chemistry, Chinese Academy of Science.

研究概述

北京生命科学研究所/清华大学生物医学交叉研究院化学中心为研究所的各实验室提供专业的化学服务并与生物实验室紧密合作开展前沿交叉课题，基于生物基础研究进展，结合现代药物研发的最新技术手段包括高通量筛选以及计算机辅助设计等开发全新的生物医药靶点，并通过化学小分子探究与调控重要的生物学途径。我们课题组核心部分主要包括：化学合成实验室，分析检测实验室和高通量筛选实验室。目前实验室研究方向主要有原子经济学有机合成方法学开发，天然产物高效或仿生全合成，利用化学生物学新策略探索小分子与靶点的相互作用鉴定药物新靶点与重要的生物学机理，以及基于新靶点的小分子药物开发。实验室开发了新颖的烷基锆广谱偶联合成方法学，首次发现了烷基锆试剂的光化学与新型自由基偶联反应途径；首次完成硼元素导向的烷基锆选择性远程迁移控制并应用到高对映选择性手性硼试剂的合成中。基于自然界丰富的天然原材料如呋喃，吲哚，单糖以及天然氨基酸等，通过分子骨架重排或者去平面化策略成功构建了以sp3杂化原子为主的三维立体“优势药效骨架”并应用到高生物活性的天然产物的全合成和仿生合成中；基于高通量筛选鉴定苗头化合物，结合构效关系和计算机辅助药物设计进行系统的药物化学开发了几类尚未满足临床需求的原创新药备选分子,如抑制乙肝病毒感染的胆酸二聚体，调节生物钟和睡眠的虫草素衍生物以及癌症治疗相关的激酶抑制剂和诱导蛋白降解或者介导蛋白蛋白相互作用的分子胶水等。我们将紧密地把有机合成，药物化学，化学生物学与生命科学相结合，从而为北京生命科学研究所建立起一套完善的化学合成与创新型药物研发平台。

Selected Publications（代表性文章）

1.Xiangbing Qi*, Wenhui Li*, “Unlocking the secrets to human NTCP structure” The Innovation, 10029

2. Chao Yang, Songlin Bai, andXiangbing Qi*, “Asymmetric synthesis alkylboranes via enantioselective cross-coupling of gem-Borazirconocene Alkanes”, manuscript in revision.

3. Peihao Chen, Jing Wang, andXiangbing Qi*, “Total Syntheses of Tetrodotoxin”, manuscript in revision.

4. Xiaolei Liu, Mingliang Lou, andXiangbing Qi*, “Asymmetric Total Syntheses of Strychnos Alkaloids via Selective Fischer Indolization”，Journal of Organic Chemistry, 2022, 87 (8), 5199-5212

5. Yan Ma*, Yang Cao, Xiaocui Song, Yuanying Zhang, Jing Li, Yankai Wang, Xiaoqing Wu, and Xiangbing Qi, “BAFinder: A software for unknown bile acid identification using accurate mass LC-MS/MS in positive and negative modes”, Analytical Chemistry 2022, 94 (16), 6242-6250

6. Daojiang Yan, Kunya Wang, Songlin Bai, Bingyu Liu, Jian Bai, Xiangbing Qi, Youcai Hu, “Flavin-Dependent Monooxygenase-Mediated 1,2-Oxazine Construction via Meisenheimer Rearrangement in the Biosynthesis of Paeciloxazine” J. Am. Chem. Soc., 2022, 144, 9, 4269-4276

7. Yue Liu, Songlin Bai, Yuanbo Du,Xiangbing Qi*, Hongyin Gao*, “Expeditious and Efficient ortho-Selective Trifluoromethane-sulfonylation of Arylhydroxylamines” Angew. Chem. Int. Ed.,2022, 61, e202115611

8. Gen Li, Mingliang Lou,Xiangbing Qi*, “A brief overview of classical natural product drug synthesis and bioactivity”, Organic Chemistry Frontiers,2022, 9, 517-571

9. Jie Chen, Nan Liu, Yinpin Huang, Yuanxun Wang, Yuxing Sun, Hong-Wei Wang*, Niu Huang*,Xiangbing Qi*and Xiaodong Wang* “Structure of PDE3A–SLFN12 complex and structure-based design for a potent apoptosis inducer of tumor cells”, Nature Communications,2021, 12:6204 | https://doi.org/10.1038/s41467-021-26546-8

10. Chao Yang, Chao Jiang,Xiangbing Qi*, “Alkylzirconocenes in Organic Synthesis: An Overview”, Synthesis 2021; 53(06): 1061-1076

11. Zilin Li, Wang Liu, Jiaqi Fu, Sen Cheng, Yue Xu, Zhiqiang Wang, Xiaofan Liu, Xuyan Shi, Yaxin Liu, Xiangbing Qi, Xiaoyun Liu*, Jingjin Ding, Feng Shao* “Shigella evades pyroptosis by arginine ADP-riboxanation of caspase-11”, Nature, 2021,290-295

12. Yang Liu, Lei Zhang, Huan Yan, Zhiqiang Wang, Guoliang Sun, Xiao Song, Zhongmin Zhou,Bo Peng, Liwei Yan, Qingcui Wu, Wenhui Li*, andXiangbing Qi*“Design of Dimeric Bile Acid Derivatives as Potent and Selective Human NTCP Inhibitors”, J. Med. Chem.,2021, 64 (20), 5973-6007.

13. Lei Zhang, Ye Zhang, Wenting Li,Xiangbin Qi, “Total Synthesis of (-)-Alstofolinine A through a Furan Oxidation/Rearrangement and Indole Nucleophilic Cyclization Cascade”Angew. Chem. Int. Ed.2019,https://doi.org/10.1002/anie.201900156.

14. Yu Zhou, Yuanxun Wang, Pengfei Li, Xi-Ping Huang,Xiangbing Qi, Yunfei Du, and Niu Huang. “Exploring Halogen Bonds in 5-Hydroxytryptamine 2B Receptor–Ligand Interactions”ACS Med. Chem. Lett.,2018, 9 (10), pp 1019–1024.

15. Chao Wei, Xiao Han, Danwei Weng, Qiru Feng,Xiangbing Qi, Jin Li & Minmin Luo. “Response dynamics of midbrain dopamine neurons and serotonin Interactions neurons to heroin, nicotine, cocaine, and MDMA”Cell Discovery，4 : 60 (2018) 1019–1024.

16. Aaron Nash,Xiangbing Qi, Pradip Maity, Kyle Owens, and Uttam K. Tambar*. “Development of the Vinylogous Pictet-Spengler Cyclization and Total Synthesis of (±)‐Lundurine A”Angew. Chem. Int. Ed.,2018, 57, 6888-6891.

17. Rui Lin, Qiru Feng, Peng Li, Ping Zhou, Ruiyu Wang, Zhe Liu, Zhiqiang Wang,Xiangbing Qi, Nan Tang, Feng Shao, Minmin Luo,“A hybridization-chain-reaction-based method for amplifying immunosignals”Nature Methods,2018(4), 275

18. Xuekai Zhang, Gang Lu, Meng Sun, Madhu Mahankali, Yanfei Ma, Mingming Zhang, Wangde Hua, Yuting Hu, Qingbing Wang, Jinghuo Chen, Gang He,Xiangbing Qi*, Weijun Shen, Peng Liu, Gong Chen，“A general strategy for synthesis of cyclophane-braced peptide macrocycles via palladium-catalysed intramolecular sp 3 C− H arylation”，Nature Chemistry，2018（10）, 540-548

19.Xueyan Ma, Peixue Li, Peihao Chen, Jinhui Li, Hongling Huang, Chao Wang, Wenjing Li, Jianping Ding, Yun Zhao, Fa-Xing Yu,Xiangbing Qi*, Lei Zhang，“Staurosporine targets the Hippo pathway to inhibit cell growth”Journal of Molecular Cell Biology,2018,10, 267-269

20. Yanli Wang, Yuze Sun, Ran Cao, Dan Liu, Yuting Xie, Li Li,Xiangbing Qi*, Niu Huang，“In Silico Identification of a Novel Hinge-Binding Scaffold for Kinase Inhibitor Discovery”J. Med. Chem.,2017, 60 (20), pp 8552-8564

21. Shih-Chia Tso, Mingling Lou, Wen-Jun Gui , Cheng-Yang Wu, Jacinta L. Chuang, Lorraine K. Morlock, Noelle S. Williams, R. Max Wynn,Xiangbing Qi*and David T. Chuang* “Development of Dihydroxyphenyl Sulfonylisoindoline Derivatives as Liver-targeting Pyruvate Dehydrogenase Kinase Inhibitors”J. Med. Chem., 2017,60 (3), 1142-1150.

22. Yaling Wu, Dingbin Tang, Na Liu, Wei Xiong, Huanwei Huang, Yang Li, Zhixiong Ma, Haijiao Zhao, Peihao Chen,Xiangbing Qiand Eric Erquan Zhang. “Reciprocal Regulation between the Circadian Clock and Hypoxia Signaling at the Genome Level in Mammals”, Cell Metabolism,2017, 25 (1),73-85.

23. Shih-chia Tso^*,Xiangbing Qi^*, Wen-Jun Gui, Jacinta L. Chuang, Lorraine K. Morlock, Amy L. Wallace, Kamran Ahmed, Sunil Laxman, Philippe M. Campeau, Brendan H. Lee, Susan M. Hutson, Benjamin P. Tu, Noelle S. Williams, Uttam K. Tambar, R. Max Wynna, and David T. Chuang. , “Structure-based Design and Mechanisms of Allosteric Inhibitors for Mitochondrial Branched-chain α-Ketoacid Dehydrogenase Kinase.”Proc. Natl. Acad. Sci. U.S.A.2013, 110, 9728-9733. (* Equal Contribution)

24. Feng Cai, Xiaotao Pu,Xiangbing Qi, Joseph. M. Ready*. “Allenes in Asymmetric Catalysis: Asymmetric Addition of Boronic Acid to α-ketoesters Catalyzed by Allene-Containing Rhodium-Phosphine Catalyst”.J. Am. Chem. Soc.,2011,133,18066-18069.

25.Xiangbing Qi, Hongli Bao, Uttam K.Tambar*. “Total Synthesis of (±)-Trigonoliimine C via Oxidative Rearrangement of an Unsymmetrical Bis-Tryptamine”,J. Am. Chem. Soc.2011,133, 10050-10053.

26. Hongli Bao,Xiangbing Qi,Uttam K.Tambar*. “Catalytic Enantioselective [2,3]-Rearrangements of Amine N-Oxides ”,J. Am. Chem. Soc.2011,133, 1206-1208.

27.Xiangbing Qi,Grant T. Rice, Manjinder S. Lall, Mark S. Plummer, M. Christina White* “Diversification of a β-lactam Pharmacophore via Allylic C–H Amination: Accelerating Effect of Lewis Acid co-catalyst”,Tetrahedron,2010,66, 4816-4826.

28. Xiaotao Pu,Xiangbing Qi,Joseph. M. Ready*. “Allenes in Asymmetric Catalysis: Asymmetric Ring Opening of meso-Epoxides Catalyzed by Allene-Containing Phosphine Oxides”J. Am. Chem. Soc.2009,131, 10364-10365.

29Xiangbing Qi,Joseph. M. Ready*. “Synthesis of Cyclopentenones from Cyclopropanes and Silyl Ynol Ethers”Angew. Chem. Int. Ed.2008,47, 7068-7070.

30.Xiangbing Qi,Joseph. M. Ready*. “Copper-Promoted Cycloaddition of Diazocarbonyl Compounds with Copper Acetylides”Angew. Chem. Int. Ed.2007,46, 3242-3244.

Patents（专利）

1. Wenhui Li,Xiangbing Qi, Yang Liu, Zhiqiang Wang, Bo Peng, Lei Zhang，“Betulinic Acid Derivatives Inhibit Hepatitis B and D Virus and NTCP Transport”. In preparation.

2.Xiangbing Qi, Ting Han, Peihao Chen, Lu Lv, Yamei Li, Longzhi Cao, Qingcui Wu, Jiaojiao Li, “A molecular glue regulating CDK12-DDB1 interaction to trigger Cycl in K degradation” PCT/CN2020/095482

3. David T. Chuang, Shih-Chia Tso,Xiangbing Qi,Wen-Jun Gui, Cheng-Yang Wu, Jacinta L. Chuang, Uttam K. Tambar, R. Max Wynn “Inhibitors of mitochondrial pyruvate dehydrogenase kinase isoforms 1-4 and uses thereof” US20170001958A1

4. Wenhui Li,Xiangbing Qi, Huan Yan, Yang Liu, Zhiqiang Wang, Bo Peng, Lei Zhang，“Polymeric Bile Acid Derivatives Inhibit Hepatitis B and D Virus and NTCP Transport”. US20170266206A1

5. Niu Huang,Xiangbing Qi, Yanli Wang, Yuze Sun. “Kinase Inhibitors”，WO2017152842A1

6.Xiangbing Qi, Mingliang Lou, Enlong Wu, Peihao Chen, Qingcui Wu, “Dihydroxyphenyl Sulfonylisoindoline Derivatives”, WO2018095260A1

7. Erquan Zhang,Xiangbing Qi, Dapeng Ju, Haijiao Zhao, Long Mei, Zhiqiang Wang, Qingcui Wu, “Adenosine Analog and its use in Regulating the Circadian Clock” WO2018133854A1