The goals of our research program are to develop new strategies and methods to facilitate the chemical synthesis of small molecules, and use these small molecules to help advance our understanding of cancer biology. We are focusing on (1) the target-oriented synthesis of structurally unique and biologically significant natural products, and (2) the function-oriented synthesis of small-molecule inhibitors of the Hedgehog (Hh) and Wnt signal transduction pathways. For the target-oriented dimension of our program, we chose to study the chemistry of steroids, alkaloids, and terpenoids. With respect to the function-oriented synthesis dimension, we are concentrating on the mechanistic and medicinal chemical studies of a series of novel Hh and Wnt antagonists. Through collaborations, we are now studying the cancer biology of the natural products and small-molecule Hh/Wnt antagonists synthesized in our lab.

  

Pblications:

 

40. Syntheses of Cyclic Guanidine-Containing Natural Products.

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

Tetrahedron 2014, DOI doi:10.1016/j.tet.2014.11.056.

  

39. 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, DOI: dx.doi.org/10.1016/j.chembiol.2014.10.013.

  

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

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

Tetrahedron 2014, DOI: 10.1016/j.tet.2014.10.027. (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. [HTML] [PDF] (supporting info) (editorial) (C&E News)

 

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

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

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

 

35. Dimeric Pyrrole–Imidazole Alkaloids: Synthetic Approaches and Biosynthetic Hypotheses.

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

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

  

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

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

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

  

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

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

Tetrahedron Lett. 2014, 55, 232–234. (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. [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. [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. [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. [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. [PDF] (supporting info) (Perspective)

 

26. Nakiterpiosin (Chapter 2).

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. [PDF] (correction) (supporting info)

 

24. The Chemistry and Biology of Nakiterpiosin.

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. [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. [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. [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.

 

20. Asymmetric Synthesis of Ageliferin.

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

J. Am. Chem. Soc. 2011, 133, 15350–15353. [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. [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. [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. [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. [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.

 

14. Synthesis and Structure Revision of Nakiterpiosin.

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

J. Am. Chem. Soc. 2009, 131, 1410–1412. [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. [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. [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. [PDF] (Addition) (supporting info)

 

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

Tan, X.; Chen, C.

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

 

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

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

Proc. Natl. Acad. Sci. 2005, 102, 3208–3212. [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. [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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