The goals of our research are to develop new chemical methods for small molecule synthesis and to use chemical approaches to understand the biological signaling pathways. Our current research projects include (1) syntheses of bioactive natural products, (2) development of biomimetic oxidation reactions, and (3) investigation of small molecule-protein interactions. In particular, we are interested in the total synthesis of marine alkaloids with unusual molecular structures, the development of new C–H oxidation catalysts, and the mechanistic and medicinal chemical studies of small molecules that modulate the activities of the Hh, Wnt and STING signaling pathways.

 

Publications:

 

54. Ketone-Catalyzed Photochemical C(sp3)–H Chlorination (Invited Article in honor of Prof. Li for 2017 Tetrahedron Young Investigator Award)

Han, L.; Xia, J.-B.; You, L.; Chen, C.

Tetrahedron 2017, 73, 3696–3701 [PMID: 28717256] (supporting info)

 

53. cGAS Is Essential for the Antitumor Effect of Immune Checkpoint Blockade

Wang, H.; Hu, S.; Chen, X.; Shi, H.; Chen, C.; Sun, Li; Chen, Z. J.

Proc. Natl. Acad. Sci. 2017, 114, 1637–1642 [PMID: 28137885] [PDF] (supporting info)

 

52. Stereocontrolled Formation of a [4.4]Heterospiro Ring System with Unexpected Inversion of Configuration at the Spirocenter

Ma, Z.; You, L.; Chen, C.

J. Org. Chem. 2017, 82, 731–736 [PMID: 27933858] [PDF] (supporting info)

 

51. Development of a Triazole Class of Highly Potent Porcn Inhibitors

You, L.; Zhang, C.; Yarravarapu, N.; Morlock, L.; Wang, X.-L.; Zhang, L.; Williams, N. S.; Lum, L.; Chen, C.

Bioorg. Med. Chem. Lett. 2016, 26, 5891–5895 [PMID: 27876319] (supporting info)

 

50. Palladium-Catalyzed C–H Arylation of 1,2,3-Triazoles (Invited Article for the Reactions of Hydrocarbons and other C-H Compounds Special Issue)

Zhang, C.; You, L.; Chen, C.

Molecules 2016, 20, 1268 [PMID: 27669198]

 

49. The past, present, and future of the Yang Reaction (Invited Review Article)

Chen, C.

Org. Biomol. Chem. 2016, 14, 8641–8647 [PMID: 27517138] [PDF]

 

48. Asymmetric Synthesis of Axinellamines A and B

Ma, Z.; Wang, X.; Ma, Y.; Chen, C.

Angew. Chem. Int. Ed. 2016, 55, 4763–4766 [PMID: 27037993] [PDF] (supporting info) (Synfacts highlight)

 

47. Chemical Disruption of Wnt-Dependent Cell Fate Decision-Making Mechanisms in Cancer and Regenerative Medicine (Invited Review Article)

Lum, L.; Chen, C.

Curr. Med. Chem. 2015, 22, 4091–4103 [PMID: 26310918]

 

46. Identification and Characterization of β-Sitosterol Target Proteins (Invited Article for the 25th Anniversary Symposium-in-Print "Recent Advances in Medicinal Chemistry and Chemical Biology")

Lomenick, B.; Shi, H.; Huang, J.; Chen, C.

Bioorg. Med. Chem. Lett. 2015, 25, 4976–4979 [PMID: 25804720] (supporting info)

 

45. 2-Hydroxyglutarate Inhibits ATP Synthase and mTOR Signaling

Fu, X.; Chin, R. M.; Vergnes, L.; Hwang, H.; Deng, G.; Xing, Y.; Pai, M. Y.; Li, S.; Ta, L.; Fazlollahi, F.; Chen, C.; Prins, R. M.; Teitell, M. A.; Nathanson, D. A.; Lai, A.; Faull, K. F.; Jiang, M.; Clarke, S. G.; Cloughesy, T. F.; Graeber, T. G.; Braas, D.; Christofk, H. R.; Jung, M. E.; Reue, K.; Huang J.

Cell Metab. 2015, 22, 508–515 [PMID: 26190651] [PDF] (supporting info)

 

44. Molecular Basis for the Specific Recognition of the Metazoan Cyclic GMP-AMP by the Innate Immune Adaptor Protein STING

Shi, H.; Wu, J.; Chen, Z. J.; Chen, C.

Proc. Natl. Acad. Sci. 2015, 112, 8947–8952 [PMID: 26150511] [PDF] (supporting info)

 

43. Syntheses of Sceptrins and Nakamuric Acid and Insights into the Biosyntheses of Pyrrole–Imidazole Dimers

Wang, X.-L.; Gao, Y.; Ma, Z.; Rodriguez, R. A.; Yu, Z.-X.; Chen, C.

Org. Chem. Front. 2015, 2, 978–984 [PMID: 26328059] [PDF] (supporting info)

 

42. Disruption of Wnt/β-Catenin Signaling and Telomeric Shortening Are Inextricable Consequences of Tankyrase Inhibition in Human Cells

Kulak, O.; Chen, H.; Holohan, B.; Wu, X.; He, H.; Borek, D.; Otwinowski, Z.; Yamaguchi, K.; Garofalo, L. A.; Ma, Z.; Wright, W.; Chen, C.; Shay, J. W.; Zhang, X.; Lum, L.

Mol. Cell Biol. 2015, 35, 2425–2435 [PMID: 25939383] [PDF] (supporting info)

 

41. Construction of the 5,6,7-tricyclic skeleton of lancifodilactone F (Invited Article for Tetrahedron Letters Symposium-in-Print in Memory of Harry Wasserman)

Shi, H.; De, S.; Wang, Q.; Gao, S.; Wang, X.; Chen, C.

Tetrahedron Lett. 2015, 56, 3225–3227 [PMID: 26097263] (supporting info)

 

40. An Approach for the Synthesis of Nakamuric Acid (Invited Article for Tetrahedron Symposium-in-Print "Synthesis of Indole/Pyrrole-Containing Natural Products")

Wang, X.-L.; Chen, C.

Tetrahedron, 2015, 71, 3690–3693 [PMID: 25983349] (supporting info)

 

39. Syntheses of Cyclic Guanidine-Containing Natural Products (Invited Review Article)

Ma, Y.; De, S.; Chen, C.

Tetrahedron 2015, 71, 1145–1173 [PMID: 25684829]

 

38. The Hedgehog Pathway Effector Smoothened Exhibits Signaling Competency in the Absence of Ciliary Accumulation

Fan, C.-W.; Chen, B.; Franco, I.; Lu, J.; Shi, H.; Wei, S.; Wang, C.; Wu, X.; Tang, W.; Roth, M. G.; Williams, N. S.; Hirsch, E.; Chen, C.; Lum, L.

Chem. Biol. 2014, 21, 1680–1689 [PMID: 25484239] [PDF] (supporting info)

 

37. Asymmetric Syntheses of Sceptrin and Massadine and Evidence for Biosynthetic Enantiodivergence

Ma, Z.; Wang, X.-L.; Wang, X.; Rodriguez, R. A.; Moore, C. E.; Gao, S.; Tan, X.; Ma, Y.; Rheingold, A. L.; Baran, P. S.; Chen, C.

Science 2014, 346, 219–224 [PMID: 25301624] [HTML] [PDF] (response to comment) (supporting info)

 

36. Visible Light-Promoted Metal-Free sp3-C–H Fluorination

Xia, J.-B.; Zhu, C.; Chen, C.

Chem. Commun. 2014, 50, 11701–11704 [PMID: 25143256] [PDF] (supporting info)

 

35. Dimeric Pyrrole–Imidazole Alkaloids: Synthetic Approaches and Biosynthetic Hypotheses (Invited Review Article)

Wang, X.; Ma, Z.; Wang, X.-L.; De, S.; Ma, Y.; Chen, C.

Chem. Commun. 2014, 50, 8628–8639 [PMID: 24828265] [PDF]

 

34. Vanadium-Catalyzed C(sp3)–H Fluorination Reactions

Xia, J.-B.; Ma, Y.; Chen, C.

Org. Chem. Front. 2014, 1, 468–472 [PMID: 24976971] [PDF] (supporting info)

 

33. A Simple Method for the Electrophilic Cyanation of Secondary Amines

Zhu, C.; Xia, J.-B.; Chen, C.

Org. Lett. 2014, 16, 247–250 [PMID: 24313859] [PDF] (supporting info)

 

32. Vanadium-Catalyzed Oxidative Strecker Reaction: α-C–H Cyanation of para-Methoxyphenyl (PMP)-Protected Primary Amines

Zhu, C.; Xia, J.-B.; Chen, C.

Tetrahedron Lett. 2014, 55, 232–234 [PMID: 24415804] (supporting info)

 

31. Visible Light-Promoted Metal-Free C–H Activation: Diarylketone-Catalyzed Selective Benzylic Mono- and Difluorination

Xia, J.-B.; Zhu, C.; Chen, C.

J. Am. Chem. Soc. 2013, 135, 17494–17500 [PMID: 24180320] [PDF] (supporting info) (Synfacts highlight)

 

30. Stromal-Epithelial Crosstalk Regulates Kidney Progenitor Cell Differentiation

Das, A.; Tanigawa, S.; Karner, C. M.; Xin, M.; Lum, L.; Chen, C.; Olson, E. N.; Perantoni, A. O.; Carroll, T. J.

Nat. Cell Biol. 2013, 15, 1035–1044 [PMID: 23974041] [PDF] (supporting info)

 

29. Cyclic GMP-AMP Containing Mixed Phosphodiester Linkages Is An Endogenous High Affinity Ligand for STING

Zhang, X.; Shi, H.; Wu, J.; Zhang, X.; Sun, L.; Chen, C.; Chen, Z. J.

Mol. Cell 2013, 51, 226–235 [PMID: 23747010] [PDF] (supporting info)

 

28. The Development of Highly Potent Inhibitors for Porcupine

Wang, X.-L.; Moon, J.; Dodge, M. E.; Pan, X.; Zhang, L.; Hanson, J.; Tuladhar, R.; Ma, Z.; Shi, H.; Williams, N. S.; Amatruda, J.; Carroll, T. J.; Lum, L.; Chen, C.

J. Med. Chem. 2013, 56, 2700–2704 [PMID: 23477365] [PDF] (supporting info)

 

27. Cyclic-GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA

Wu, J.; Sun, L.; Chen, X.; Du, F.; Shi, H.; Chen, C.; Chen, Z. J.

Science 2013, 339, 826–830 [PMID: 23258412] [PDF] (supporting info)(Perspective)

 

26. Nakiterpiosin (Invited Book Chapter)

Gao, S.; Chen. C.

In Total Synthesis of Natural Products–At the Frontiers of Organic Chemistry; Li, J. J., Corey, E. J., Eds.; Springer-Verlag: Berlin/Heidelberg, 2013; pp 25–38

 

25. A Biomimetic Route for the Construction of the [4+2] and [3+2] Core Skeletons of the Dimeric Pyrrole–Imidazole Alkaloids and the Asymmetric Synthesis of Ageliferins

Wang, X.; Wang, X.-L.; Tan, X.; Lu, J.; Cormier, K. W.; Ma, Z.; Chen. C.

J. Am. Chem. Soc. 2012, 134, 18834–18842 [PMID: 23072663] [PDF] (correction) (supporting info)

 

24. The Chemistry and Biology of Nakiterpiosin (Invited Review Article)

Gao, S.; Wang, Q.; Wang, G.; Lomenick, B; Liu, J.; Fan, C.-W.; Deng, L.-W.; Huang, J.; Lum, L.; Chen. C.

Synlett 2012, 23, 2298–2310 [PMID: 23226922] [PDF]

 

23. A Highly Selective Vanadium Catalyst for Benzylic C–H Oxidation

Xia, J.; Cormier, K. W.; Chen, C.

Chem. Sci. 2012, 3, 2240–2245 [PMID: 22712051] [PDF] (supporting info)

 

22. Diverse Chemical Scaffolds Support Direct Inhibition of the Membrane Bound O-Acyltransferase Porcupine

Dodge, M. E.; Moon, J.; Tuladhar, R.; Lu, J.; Jacob, L. S.; Zhang, L.-s.; Shi, H.; Wang, X.-L.; Moro, E.; Mongera, A.; Argenton, F.; Karner, C. M.; Carroll, T. J.; Chen, C.; Amatruda, J. F.; Lum, L.

J. Biol. Chem. 2012, 287, 23246–23254 [PMID: 22593577] [PDF]

 

21. In Vivo Wnt Signaling Tracing through a Transgenic Biosensor Fish Reveals Novel Activity Domains

Moro, E.; Ozhan-Kizil, G.; Mongera, A.; Beis, D.; Wierzbicki, C.; Young, R. M.; Bournele, D.; Domenichini, A.; Valdivia, L. E.; Lum, L.; Chen, C.; Amatruda, J. F.; Tiso, N.; Weidinger, G.; Argenton, F.

Dev. Biol. 2012, 366, 327–340 [PMID: 22546689]

 

20. Asymmetric Synthesis of Ageliferin

Wang, X.; Ma, Z.; Lu, J.; Tan, X.; Chen, C.

J. Am. Chem. Soc. 2011, 133, 15350–15353 [PMID: 21888421] [PDF] (supporting info)

 

19. Canonical Wnt9b Signaling Balances Progenitor Cell Expansion and Differentiation During Kidney Development

Karner, C. M.; Das, A.; Ma, Z.; Self, M.; Chen, C.; Lum, L.; Oliver, G.; Carroll T. J.

Development 2011, 138, 1247–1257 [PMID: 21350016] [PDF]

 

18. Revisiting the Kinnel–Scheuer Hypothesis for the Biosynthesis of Palau'amine (Invited Article for the Emerging Investigator Special Issue)

Ma, Z.; Lu, J.; Wang, X.; Chen, C.

Chem. Commun. 2011, 47, 427–429 [PMID: 20848010] [PDF] (supporting info)

 

17. Tankyrase Is Necessary for Canonical Wnt Signaling during Kidney Development

Karner, C. M.; Michael Dodge, C. E.; Ma, Z.; Lu, J.; Chen, C.; Lum, L.; Carroll, T. J.

Dev. Dyn. 2010, 239, 2014–2023 [PMID: 20549720] [PDF]

 

16. Chemical and Biological Studies of Nakiterpiosin and Nakiterpiosinone

Gao, S.; Wang, Q.; Huang, L. J.; Lum, L.; Chen, C.

J. Am. Chem. Soc. 2010, 132, 371–383 [PMID: 20000429] [PDF] (supporting info)

 

15. Structure/Activity Relationship Studies of Small-Molecule Inhibitors of Wnt Response (Invited Article in honor of Prof. Barbas for 2009 Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry)

Lu, J.; Ma, Z.; Hsieh, J.-C.; Fan, C.-W.; Chen, B.; Longgood, J. C.; Williams, N. S.; Amatruda, J. F.; Lum, L.; Chen, C.

Bioorg. Med. Chem. Lett. 2009, 19, 3825–3827 [PMID: 19410457]

 

14. Synthesis and Structure Revision of Nakiterpiosin

Gao, S.; Wang, Q.; Chen, C.

J. Am. Chem. Soc. 2009, 131, 1410–1412 [PMID: 18998640] [PDF] (supporting info) (cover picture) (Synfacts highlight)

 

13. Small Molecule-mediated Disruption of Wnt-dependent Signal Transduction in Tissue Regeneration and Cancer

Chen, B.; Dodge, M. E.; Tang, W.; Lu, J.; Ma, Z.; Fan, C.-W.; Wei, S.; Hao, W.; Kilgore, J. A.; Williams, N. S.; Roth, M. G.; Amatruda, J. F.; Chen, C.; Lum, L.

Nat. Chem. Biol. 2009, 5, 100–107 [PMID: 19125156] [PDF] (supporting info) (News and Views)

 

12. On the Potent Inhibitors of the Hedgehog Signaling Pathway (Invited Condensation and Commentary)

Chen, C.

Chemtracts–Org. Chem. 2008, 21, 150–154

 

11. Nickel-Catalyzed Carbonylative Negishi Cross-Coupling Reactions

Wang, Q.; Chen, C.

Tetrahedron Lett. 2008, 49, 2916–2921 (Synfacts highlight)

 

10. An Approach to the Core Skeleton of Lancifodilactone F

Wang, Q.; Chen, C.

Org. Lett. 2008, 10, 1223–1226 [PMID: 18303901] [PDF] (supporting info)

 

9.  Palladium-Catalyzed Direct Functionalization of Imidazolinone: Synthesis of Dibromophakellstatin

Lu, J.; Tan, X.; Chen, C.

J. Am. Chem. Soc. 2007, 129, 7768–7769 [PMID: 17539649] [PDF] (Addition) (supporting info)

 

8.  Regiocontrol in Manganese(III)-Mediated Oxidative Heterobicyclizations: Access to the Core Skeletons of roidin Dimers

Tan, X.; Chen, C.

Angew. Chem. Int. Ed. 2006, 45, 4345–4348 [PMID: 16739146] [PDF] (supporting info)

 

7.  Convergent Diversity-Oriented Synthesis of Small-Molecule Hybrids

Chen, C.; Li, X.; Neumann, C. S.; Lo, M. M.-C.; Schreiber, S. L.

Angew. Chem. Int. Ed. 2005, 44, 2249–2252 [PMID: 15747386] [PDF] (supporting info)

 

6.  Label-free Detection of Small-molecule–Protein Interactions by Using Nanosensors

Wang, W. U.; Chen, C.; Lin, K.-h.; Fang, Y.; Lieber, C. M.

Proc. Natl. Acad. Sci. 2005, 102, 3208–3212 [PMID: 15716362] [PDF]

 

5.  Catalytic Asymmetric [3+2] Cycloaddition of Azomethine Ylides. Development of a Versatile Stepwise, Three-Component Reaction for Diversity-Oriented Synthesis

Chen, C.; Li, X.; Schreiber, S. L.

J. Am. Chem. Soc. 2003, 125, 10174–10175 [PMID: 12926931] [PDF] (supporting info)

 

4.  Abnormal and Regioselective Wacker Oxidation of 1,5-Diene

Ho, T.-L.; Chang, M.; Chen, C.

Tetrahedron Lett. 2003, 44, 6955–6957

 

3.  Synthesis of (+)-CP-263,114

Chen, C.; Layton, M. E.; Sheehan, S. M.; Shair, M. D.

J. Am. Chem. Soc. 2000, 122, 7424–7425 [PDF] (supporting info)

 

2.  Chelation-Assisted Regioselective C–O Bond Cleavage Reactions of Acetals by Grignard Reagents. A General Procedure for the Regioselective Synthesis of Protected Polyols Having One Free Hydroxy Group

Cheng, W.-L.; Shaw, Y.-J.; Yeh, S.-M.; Kanakamma, P. P.; Chen, Y.-H.; Chen, C.; Shieu, J.-C.; Yiin, S.-J.; Lee, G.-H.; Wang, Y.; Luh, T.-Y.

J. Org. Chem. 1999, 64, 532–539 [PDF]

 

1. Stereospecific Synthesis of the CP-263,114 Core Structure

Chen, C.; Layton, M. E.; Shair, M. D.

J. Am. Chem. Soc. 1998, 120, 10784–10785 [PDF] (supporting info)

 

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