Xiaoguang Lei, Ph.D. - Scientists&Research - 北京生命科学研究所

Xiaoguang Lei, Ph.D.

Associate Investigator, NIBS, Beijing, China

Phone：010-80704786

Fax： 010-80704785

E-mail：leixiaoguang@nibs.ac.cn

Education:

2001

B.S. in Chemistry, Peking University, Beijing, China

2006
Ph.D. in Organic Chemistry, Boston University, Boston, USA

Professional Experience:

2013-present
Associate Investigator and Director of Chemistry Center, NIBS

2008-2012
Assistant Investigator and Director of Chemistry Center, NIBS

2006-2008
Postdoctoral Fellow, Columbia University and Memorial Sloan-Kettering Cancer Center (MSKCC), New York, USA

Research Description

Many critical biological processes are conducted by small molecules and so they can arguably be regarded as another essential component of the “central dogma” of molecular biology. Biologically meaningful small molecules may be natural products, which are discovered by nature through many cycles of diversity generation and natural selection, or they may be prepared through organic synthesis for the development of drug candidates or chemical probes to study life’s processes. Therefore, organic synthesis is an important discipline that continues to play a vital role in drug discovery and in the allied fields of medicine and biology. New small molecules are needed to function as probes to further study the known biological pathways, to discover novel pathways and interactions, to validate potential drug targets, and to treat unmet medical needs as drugs. Accordingly, the central theme of our research focuses on the efficient synthesis of these small molecules, as well as the subsequent biological evaluations of these molecules applying medicinal chemistry and chemical biology approaches. We also hope to facilitate the synergy between synthetic chemistry and biological sciences at NIBS by creating a research environment in which new scientific collaborations are possible.

Publications

1. Li, Q.; Dong, T.; Liu, X.; Lei, X.* “A Bioorthogonal Ligation Enabled by Click Cycloaddition of o-Quinolinone Quinone Methide and Vinyl Thioether” J. Am. Chem. Soc. 2013, DOI: 10.1021/ja401989p.

2. Li, C.; Dong, T.; Dian, L.; Zhang, W.; Lei, X.* “Biomimetic Syntheses and Structural Elucidation of the Apoptosis-Inducing Sesquiterpenoid Trimers: (-)-Ainsliatrimers A and B” Chem. Sci. 2013, 4, 1163-1167.

3. Wang, G.; Wang, X.; Yu, H.; Wei, S.; Williams, N.; Holmes, D. L.; Halfmann, R.; Naidoo, J.; Wang, L.; Li, L.; Chen, S.; Harran, P.; Lei, X.*; Wang, X.* “Small Molecule Activation of the TRAIL Receptor DR5 in Human Cancer Cells” Nat. Chem. Biol. 2013, 2, 84-90. (News stories describing this work were highlighted inChem. & Eng. News 2013, 2, 37; Nature Asia 2012, December 24).

4. Huang, J.; Lei, X.* “A Nature-inspired Concise Synthesis of (+)-ent-Chromazonarol” Sci. China Chem. 2013, 56, 349-353.

5. Li, H.; Wang, X.; Hong, B.; Lei, X.* “Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (-)-Lycojapodine A” J. Org. Chem. 2013, 78, 800-821. (Featured and Cover Article).

6. 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.

7. 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.

8. Lei, X.*; Li, H. “Selective Alkene Metathesis in the Total Synthesis of Complex Natural Product” Top. Curr. Chem. 2012, 327, 163-196.

9. Sun, L.; Wang, H.; Wang, Z.; He, S.; Chen, S.; Liao, D.; Wang, L.; Yan, J.; Liu, W.;Lei, X.*; Wang, X.* “Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of RIP3 Kinase” Cell 2012, 148, 213-227. (News stories describing this work were highlighted in Chem. & Eng. News 2012, 5, 40; Nature China 2012, February 1; Asian Scientist 2012, January31; and Nature Reviews Molecular Cell Biology, 2012, Feb. 8).

10. Li, H.; Wang, X.; Lei, X.* “Total Syntheses of Lycopodium Alkaloids (+)-Fawcettimine, (+)-Fawcettidine and (-)-8-Deoxyserratinine” Angew. Chem. Int. Ed. 2012, 51, 491-495; Angew. Chem. 2012, 124, 506-510.

11. Liao, D.; Li, H.; Lei, X.* “Efficient Generation of ortho-Quinone Methide: Application to the Biomimetic Syntheses of (±)-Schefflone and Tocopherol Trimers” Org. Lett.2012, 14, 18-21.

12. 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.

13. Chou, T.; Dong, H.; Zhang, X.; Lei, X.; Hartung, J.; Zhang, Y.; Lee, H. L.; Wilson, R. M.; Danishefsky, S. J. * “Multifaceted Cytoprotection by Synthetic Polyacetylenes Inspired by the Ginseng-derived Natural Product Panaxytriol” Proc. Natl. Acad. Sci. USA 2011, 108, 14336-14341.

14. Li, C.; Yu, X.; Lei, X.* “A Biomimetic Total Synthesis of (+)-Ainsliadimer A” Org. Lett. 2010, 12, 4284-4287.

15. Gong, Y.; Wang, X.; Wang, J.; Yang, Z.; Li, S.; Yang, J.; Liu, L.; Lei, X.*; Shao, F. * “Chemical Probing Reveals Insights into the Signaling Mechanism of Inflammasome Activation” Cell Res. 2010, 20, 1289-1305.

16. Han，Z.; Niu, T.; Chang, J.; Lei, X.; Zhao, M.; Wang, Q.; Cheng, W.; Wang, J.; Feng, Y.; Chai, J.* “Crystal structure of the FTO protein reveals basis for its substrate specificity” Nature 2010, 464, 1205-1209.

17. Lee, L. S.; Stephenson, K. K.; Fahey, J. W.; Parsons, T. L.; Lietman, P. S.; Andrade, A. S.; Lei, X. Yun, H.; Soon, G.H.; Shen, P.; Danishefsky, S. J.*; Flexner, C.* “Induction of Chemoprotective Phase 2 Enzymes by Ginseng and its Components” Planta Med. 2009; 75, 1129-1133

18. Lei, X.; Danishefsky, S. J.* “Efficient Synthesis of a Novel Resorcyclide as Anticancer Agent Based on Hsp90 Inhibition” Adv. Synth. Catal. 2008, 350, 1677-1681

19. Lei, X.; Dai, M.; Hua, Z.; Danishefsky, S. J.* “Biomimetic Total Synthesis of Tricycloillicinone and Mechanistic Studies Toward the Rearrangement of Prenyl Phenyl Ethers” Tetrahedron Lett. 2008, 49, 6383-6385

20. Ng, F.; Yun, H.; Lei, X.; Danishefsky, S. J.; Fahey, J.; Stephenson, K.; Flexner, C.; Lee, L.* “(3R,9R,10R)-Panaxytriol: a molecular-based nutraceutical with possible application to cancer prevention and treatment” Tetrahedron Lett. 2008, 49, 7178-7179

21. Peng, L. F.; Kim, S. S.; Matchacheep, S.; Lei, X.; Su, S.; Lin, W.; Runguphan, W.; Choe, W. H.; Sakamoto, N.; Beeler, A. B.; Porco, J. A., Jr.; Schreiber, S. L.* and Chung, R. T.* “Identification of Novel Epoxide Inhibitors of HCV Replication Using High-Throughput Screening.” Antimicrob. Agents Chemother. 2007, 51, 3756-3759.

22. Lei, X.; Porco, J. A., Jr.* “Total Synthesis of the Diazobenzofluorene Antibiotic (-)-Kinamycin C.” J. Am. Chem. Soc. 2006, 128, 14790-14791. (News story describing this work was highlighted in Chem. & Eng. News 2006, 45, 9.)

23. Porco, J. A., Jr.*; Su, S.; Lei, X.;Bardhan, S.; Rychnovsky, S. D. “Total Synthesis and Structure Assignment of (+)-Hexacyclinol” Angew. Chem. Int. Ed. 2006, 45, 5790-5792; Angew. Chem. 2006, 118, 5922-5924. (News stories describing this work were reported in Chem. & Eng. News 2006, 31, 11 and Nature 2006, 442, 492-493)

24. Lei, X.; Zaarur, N.; Sherman, M. Y.; Porco, J. A., Jr.* “Stereocontrolled Synthesis of a Complex Chemical Library via Elaboration of Angular Epoxyquinol Scaffolds.” J. Org. Chem. 2005, 70, 6474-6483.

25. Su, S.; Aquilano, D.; Arumugasamy, J.; Beeler, A. B.; Eastwood, E. L.; Giguere, J. R.; Lan, P.; Lei, X.; Min, G. K.; Yeager, A. R.; Zhou, Y.; Panek, J. S.; Snyder, J. K.; Schaus, S. E.; Porco, J. A., Jr.* “Convergent Synthesis of a Complex Oxime Library Using Chemical Domain Shuffling.” Org. Lett. 2005, 7, 2751-2754.

26. Lei, X.; Porco, J. A., Jr.* “Synthesis of a Polymer-Supported Anthracene and Its Application as a Dienophile Scavenger.” Org. Lett. 2004, 6, 795-798.

27. Lei, X.; Johnson, R. P.; Porco, J. A., Jr.* “Total Synthesis of the Ubiquitin-Activating Enzyme Inhibitor (+)-Panepophenanthrin.” Angew. Chem. Int. Ed. 2003, 42, 3913-3917; Angew. Chem. 2003, 115, 4043-4047. (This publication was highlighted as a “Hot Paper”.)

Patents

1. Danishefsky, S. J.; Yun, H.; Chou, T.; Lei, X.; Sames, D. “Compounds and methods for treating cancer or neurotrophic disorder.” US2011/0124690

2. Danishefsky, S. J.; Chou, T.; Lei, X.; Yun, H.; Ng, F.; Hartung, J.; Sames, D. “Compounds, compositions and methods for reducing toxicity and treating or preventing diseases.” PCT Int. Appl. 2010, WO2010025272

3. Danishefsky, S. J.; Chou, T.; Lei, X. “Compounds, compositions and methods for treating or preventing diseases.” PCT Int. Appl. 2009, WO2009105123

4. Cottarel, G.; Gardner, T.; Lei, X.; Porco, J.; Schaus, S.; Wierzbowski, J. “Compositions and methods for potentiating antibiotic activity using an ATP receptor antagonist, coumarin, flavone, or terpene” PCT Int. Appl., 2008, WO2008019292

5. Danishefsky, S. J. Lei, X.; Yun, H.; Chou, T. “Compositions and methods using a panaxytriol compound in combination with a tubulin-binding drug for treating cancer or a neurotrophic disorder.” PCT Int. Appl. 2008, WO 2008103916


2001	B.S. in Chemistry, Peking University, Beijing, China
2006	Ph.D. in Organic Chemistry, Boston University, Boston, USA


2013-present	Associate Investigator and Director of Chemistry Center, NIBS
2008-2012	Assistant Investigator and Director of Chemistry Center, NIBS
2006-2008	Postdoctoral Fellow, Columbia University and Memorial Sloan-Kettering Cancer Center (MSKCC), New York, USA