Research Interests
My group seeks to overcome current challenges in innovative drug discovery by focusing our efforts on the following two topics: (1) Metal nanocomposite catalyzed organic reaction. We use metal nanocatalysts to address important synthetic needs in fine chemicals and pharmaceuticals. Based on their controllable fabrication, we have been discovering highly efficient and selective organic transformations by effectively controlling the activity of the metal nanocatalysts. Our efforts also include the synthetic methodology of silicon containing compounds and their chemical biology applications; (2) Fragment Based Drug Discovery. We employ fragment screening and structure-based drug design towards the discovery of selective modulator of novel protein targets with low druggability (e.g. bromodomain proteins, deubiquitinases), which enables related chemical biological and early drug discovery study.
Scientific Contributions
The 'silicon swap strategy' entails the replacement of a carbon atom by a silicon atom in a given drug molecule. Such a strategy has been conceived as a reasonable and appealing way to invent new drugs. However, the development of such a strategy has become stagnant mainly due to the lack of efficient synthetic method. We developed a series new reactions that provides easier and versatile access to silicon containing compounds, including chiral silicons. We also demonstrated that such a strategy could be employed in the discovery of investigational drug molecules. In our approach, we use a number of interdisciplinary methods including nanomaterial, organic and medicinal chemistry, as well as fragment lead discovery. Our research has significantly expand the utility of new tools in drug discovery.
Selected Achievements
1. (Nano) metal catalysis. We took advantage of well-defined metal nanoparticles and studied their Structure-Activity Relationship (SAR) in a number of reactions. We used the derived SAR to guide the rational design of metal nanoparticle catalysis for the target reactions. Along this line, we had developed optimal catalysts for selective hydrogenation reactions (J. Am. Chem. Soc. 2012, 134, 8975; ACS Catalysis, 2013, 3, 608; Chem. Comm. 2013, 49, 6843.), aerobic oxidation reactions (ACS Catalysis, 2013, 3, 478; ACS Catalysis, 2013, 3, 1681), Si-H activation reactions (Angew. Chem. Int. Ed., 2015, 54, 6918; Nano Research 2015, 8, 1365), as well as Si-C bond activation reactions (Angew. Chem. Int. Ed. 2014, 53, 5667; Synlett 2015, 26, 1145; Angew. Chem. Int. Ed. 2016, in press; Chem. Commun. 2015, 51, 17410).
2. Synthesis of silicon containing compounds. We developed efficient syntheses of α-silyl amines and β-silyl amines (Asian. J. Org. Chem. 2014, 3, 851; Chem. Comm. 2016, 52, 7862 – 7865). We also devised the syntheses of α- andβ- silyl amino acids and prepared the first silicon containing proteins.
3. We discovered a novel small molecule inhibitor KQ72 that has the potential to precisely treat a subtype of non-small cell lung cancer (China Patent: 201510925699.7). We demonstrated for the first time the advantages of a “silicon swap” compound in preclinical studies.
Selected Publications
1.Liu, C.; Zhang, Q.; Li, H.; Guo, S.; Xiao, B.; Deng, W.; Liu, L.;
*He, W. Cu/Fe Catalyzed Intermolecular Oxidative Amination of Primary Benzylic C-H Bonds.
Chem. Eur. J.
2016, DOI: chem.201600107. (HOT paper)
2.Zhang, Q.-W.; An, K.; Liu, L.-C.; Guo, S.; Jiang, C.; Guo, H.;
*He, W. Silacyclobutane: a New C-H Silylation Reagent.
Angew. Chem. doi
：
10.1002/anie.201602376
3.Zhao, C.; Liu, L-C.; Wang, J.; Jiang, C.; Zhang, Q.-W.;
*He, W.
Rh(I)-Catalyzed Insertion of Allenes into C−C Bonds of Benzocyclobutenols.
Org. Lett.
2016,
18, 328-331.
4.Guo, H.; Chen, X.; Zhao, C.;
*He, W. Suzuki-type Cross Coupling between Aryl Halides and Silylboranes for the Syntheses of Aryl Silanes.
Chem. Commun.
2015,
51, 17410 – 17412.
5.Ji, Y.; Wu, Y.; Zhao, G.; Wang, D.; Liu, L.;
He, W.; *Li, Yadong.
Porous bimetallic Pt-Fe nanocatalysts for highly efficient hydrogenation of acetone.
Nano Research
2015.
8, 2706-2713.
6.Zhang, Q.; An, K.;
*He, W.
Rh Catalyzed Enantioselective Intramolecular C-H Silylation for the Syntheses of Planar Chiral Metallocene Siloles.
Angew. Chem. Int. Ed.,
2015,
54, 6918-6921.
7.Guo, H.; Xiuling Y;, Zhi, Y.; Li，Z.; Wu, C.; Zhao, C.; Wang, J.; Yu, Z.; *Ding, Y.;
*He, W.; Li. Y.
Nanostructuring Gold Wires for Highly Durable Nanocatalysts toward Selective reduction of nitro compounds and azides with organosilanes.
Nano Research
2015,
8, 1365-1372 (Cover story)
8.Xiao, B.; Niu, Z.; Wang, Y.; Jia, W.; Shang, J.; Zhang, L.; Wang, D.; Fu, Y.; Zeng, J.;
He, W.; Wu, K.; Li, J.; Yang, J.; *Liu, L.; *Li, Y.
Copper Nanocrystal Plane Effect on Stereoselectivity of Catalytic Deoxygenation of Aromatic Epoxides.
J. Am. Chem. Soc.
2015,
137, 3791-3794.
9.Zhang, Q.; An, K.;
*He, W.
Catalytic Synthesis of π-Conjugated Silole through Si-C (sp3) Bond Activation.
Synlett,
2015,
26, 1145-1152.
10.Dang, S.; Wu, S.; Wang, J.; Li, H.; Huang, M.;
He, W.; Li, Y.; Wong, C. C. L.; *Shi, Y.
Cleavage of amyloid precursor protein by an archaeal presenilin homologue PSH.
PNAS
2015,
112, 3344-3349.
11.Zhao, C.; Jiang, C.; Wang, J.; Wu, C.; Zhang, Q.;
*He, W.
Enantioselective Syntheses of α-Silyl Amines via a Copper-N-HeterocyclicCarbene Catalyzed Nucleophilic Silicon Transfer to Imines.
Asian. J. Org. Chem.
2014,
3, 851-855. (Cover story)
12.Zhang, Z.; Chen, Y.; He, S.; Zhang, J.; Xu, X.; Yang, Y.; Nosheen, F.; Saleem, F.;
He, W.;*Wang, X.
Hierarchical Zn/Ni-MOF-2 Nanosheet-Assembled Hollow Nanocubes for Multicomponent Catalytic Reactions.
Angew. Chem. Int. Ed.,
2014,
53, 12517-12521.
13.Zhang, Q.; An, K.;
*He, W.
Rh Catalyzed Tandem Cyclization/Si-C Activation Reaction for the Synthesis of Siloles.
Angew. Chem. Int. Ed.
2014,
53, 5667-5671.
14.Zhang, Z.; Chen, Y.; Xu, X.; Zhang, J.; Xiang, G.;
He, W.; *Wang, X.
Well-Defined Metal-Organic Framework Hollow Nanocages.
Angew. Chem. Int. Ed.,
2014,
53, 429-433.
15.Li, L.; Niu, Z.; Cai, S.; Zhi, Y.; Li, H.; Rong, H.; Liu, L.; Liu, L.;
*He, W.; *Li, Y.
A PdAg Bimetallic Nanocatalyst for Selective Reductive Amination of Nitroarenes.
Chem. Comm.
2013,
49, 6843.
16.Zhang, Q.; Cai, S.; Li, L.; Chen, Y.; Rong, H.; Niu, Z.; Liu, J.;
*He, W.; *Li, Y.
Direct Syntheses of Vinyl Ethers from Benzyl Alcohols via Ag Nanoparticles Catalyzed Tandem Aerobic Oxidation.
ACS Catalysis,
2013,
3, 1681-1684.
17.Liu, J.; *Liu, C.;
*He, W.
Fluorophores and Their Applications as Molecular Probes in Living Cells.
Current Organic Chemistry
2013, 17, 564-579.
18.Huang, W.; Choi, W.; Chen, Y.; Zhang, Q.; Deng, H.;
He, W.; *Shi, Y.
A Proposed Role for Glutamine in Cancer Cell Growth through Acid Resistance.
Cell Research
2013,
23, 724-727.
19.Cai, S.; Duan, H.; Rong, H.; Wang, D.; Li, L.;
*He, W.; *Li, Y.
Highly Active and Selective Catalysis of Bimetallic Rh3Ni1 Nanoparticles in the Hydrogenation of Nitroarenes
ACS Catalysis,
2013,
3, 608-612.
20.Cai, S.; Rong, H.; Yu, X.; Liu, X.; Wang, D.;
*He, W.; *Li, Y.
Room Temperature Activation of Oxygen by Monodispersed Metal Nanoparticles: Oxidative Dehydrogenative Coupling of Anilines for Azobenzene Syntheses.
ACS Catalysis,
2013,
3, 478-486.
21.Wu, Y.; Cai, S.; Wang, D.; *
He, W.; *Li, Y.
Syntheses of Water-Soluble Octahedral, Truncated Octahedral and Cubic Pt−Ni Nanocrystals and Their Structure−Activity Study in Model Hydrogenation Reactions.
J. Am. Chem. Soc.
2012.
134, 8975-8981.
22. Niu, Z.; Peng, Q.; Zhuang, Z.;
*He, W.; *Li, Y.
Evidence of an Oxidative-Addition-Promoted Pd-Leaching Mechanism in the Suzuki Reaction by Using a Pd-Nanostructure Design.
Chem. Eur. J.
2012,
18, 9813-9817.
