研究概述 Research
Description
化学小分子在认知,干扰与调节生物过程中发挥着重要的作用。我们课题组致力于在开拓合成化学空间的基础上,利用获得的活性小分子发现与人类重大疾病相关的药物作用靶标和先导化合物。同时设计合成具有重要生物学利用价值的化学工具分子。具体的研究内容包括:
(1)利用新型催化体系研究新颖的化学键构建方法,为化学分子的合成提供更理想的策略。
(2)选择与重大疾病相关的天然产物进行合成及活性优化,进而推动创新药物的研究;
(3)探索活性天然小分子的生物学作用机制和其作用靶标;
(4)设计合成能够选择性标记,追踪生物大分子或识别其相互作用的化学工具分子。
我们实验室诚挚地欢迎想利用化学手段解决生物学问题的科学家加入。
Small molecules are of paramount importance in the recognition,
modulation and regulation of biological processes. The research of our group
explores the interface between chemical synthesis and biology, by pursuing the
efficient synthesis of structurally novel and therapeutically potent small
molecules prior to probing their mechanism of action and functional targets.
Our specific research interests include the following:
• Development of new catalytic reactions for the efficient
construction of chemical bonds, thereby providing practical synthetic methods
for “ideal synthesis”.
• Total synthesis of structurally complex and bioactive natural
products.
• Exploring the mechanism of action and the functional targets of
bioactive small molecules.
• Development of novel molecular probes to study the interactions
between biological macromolecules.
代表文章Representative Publications
1. Li, C.#; Kawamata, Y.#; Nakamura, H.; Vantourout, J. C.; Liu, Z.; Hou, Q.; Bao, D.; Star, J. T.; Chen, J.; Yan, M.; Baran, P. S.* “Electrochemically Enabled, Ni-Catalyzed Amination” Angew. Chem. Int. Ed. 2017, in press
2. Li, C.#; Wang, J.#; Barton, L. M.; Yu, S.; Tian, M.; Peters, D. S.; Kumar, M.; Yu, A. W.; Johnson, K. A.; Chatterjee, A. K.; Yan, M.; Baran, P. S.* “Decarboxylative Borylation” Science, 2017, 356, 1045.
3. Qin, T.#; Cornella, J.#; Li, C.#; Malins, L. R.; Edwards, J. T.; Kawamura, S.; Maxwell, B. D.; Eastgate, M. D.; Baran, P. S.* “A General Alkyl-Alkyl Cross-Coupling Enabled by Redox-Active Esters and Alkylzinc Reagents” Science 2016, 352, 801-805
4. Li, C.; Jones, A. X.; Lei, X.* “Synthesis and Mode of Action of Oligomeric Sesquiterpene Lactones” Nat. Prod. Rep. 2016, 33, 602-611.
5. Li, D.#; Li, C.#; Li, L.; Chen, S.; Wang, L.; Li, Q.; Wang, X.; Lei, X.*; Shen, Z.* “Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis” Cell Chemical Biology 2016, 23, 257-266.
6. Hong, B.#; Li, C.#; Wang, Z.; Chen, J.; Li, H.*; Lei, X.* “Enantioselective Total Synthesis of (−)-Incarviatone A” J. Am. Chem. Soc. 2015, 137, 11946-11949.
7. Dao, H. T.; Li, C.; Michaudel, Q.; Maxwell, B. D.; Baran, P. S.* “Hydromethylation of Unactivated Olefins” J. Am. Chem. Soc. 2015, 137, 8046-8049.
8. Dong, T. #; Li, C. #; Wang, X.; Dian, L.; Zhang, X.; Li, L.; Chen, S.; Cao, R.; Li, L.; Huang, N.; He, S.;* Lei, X.* “Ainsliadimer A Selectively Inhibits IKKα/β by Covalently Binding a Conserved Cysteine” Nature Commun. 2015, 6, 6522.
9. Li, C.#; Dong, T.#; Li, Q.; Lei, X.* “Probing the Anticancer Mechanism of (−)-Ainsliatrimer A through Diverted Total Synthesis and Bioorthogonal Ligation” Angew. Chem. Int. Ed. 2014, 53, 12111-12115.
10. Li, C.; Lei, X.* “Strategies toward the Biomimetic Syntheses of Oligomeric Sesquiterpenoids” J. Org. Chem. 2014, 79, 3289-3295.
11. Li, C.; Dong, T.; Dian, L.; Zhang, W.; and Lei, X.* “Biomimetic Syntheses and Structural Elucidation of the Apoptosis-Inducing Sesquiterpenoid Trimers: (-)-Ainsliatrimers A and B” Chem. Sci. 2013,4, 1163-1167.
12. Li, C.; Li, X.; Wang, X.; Lei, X.* “Diversity-oriented Synthesis of Bicyclic Ring Systems via a Conjugate Addition/aldol/RCM Process” Sci. China. Chem. 2013, 56, 337-341.
13. Li, C.; Dian, L.; Zhang, W.; Lei, X.* “Biomimetic Syntheses of (-)-Gochnatiolides A-C and (-)-Ainsliadimer B” J. Am. Chem. Soc. 2012, 134, 12414-12417.
14. Li, C.; Tu, S.; Wen, S.; Li, S.; Chang, J.; Shao, F, Lei, X.* “Total Synthesis of the G2/M DNA Damage Checkpoint Inhibitor Psilostachyin C” J. Org. Chem. 2011, 76, 3566-3570.
15. Li, C.; Yu, X.; Lei, X.* “A Biomimetic Total Synthesis of (+)-Ainsliadimer A” Org. Lett. 2010, 12, 4284-4287.
专利Patents
1. Lei, X.; He, S.; Li, C.; Dong, T. “Sesquiterpenoids” PCT/CN2014/076123. US Pat No. 9670226.
2. Baran, P. S.; Li, C.; Wang, J.; Chatterjee, A. K.; Kumar, M.; Yu, S.; Johnson, K. A.; “Decarboxylative Borylation” under review.