♦ 课题组成员

孙健研究员	卢晓霞研究员	唐亚雄副研究员	周莉研究实习员

♦ 主要研究进展和成果

 　　针对不对称亚胺还原、分子间直接Aldol以及Michael加成等手性合成反应，围绕催化剂的发展，开展了深入和系统的研究工作，取得了一系列高水平的研究成果。尤其是在手性路易斯碱催化三氯硅烷不对称氢转移还原反应研究领域，取得了突出的成绩，并已形成了自己的研究特色，不但使对该类反应的研究获得了突破性进展，同时也使其发展成为了一类高效、高对映选择性和高底物适应性并具有广阔应用前景的有机化学反应。相关研究已在包括Org. Lett.、Chem. Eur. J、Adv. Synth. Catal.、Chem. Commun.在内的国际主流期刊上发表了8篇系列SCI论文，并受到了国际同行的关注，其中有3篇论文工作分别被SYNFACTS和Nature China杂志专题报道并作为亮点介绍，有2篇研究论文工作被Organic Chemistry Portal专题收录。目前本研究小组已成为三氯硅烷不对称氢转移还原反应研究领域国际上最重要的研究小组之一。

　　运用现代药物设计理念，发展了一系列新型血管紧张素II受体拮抗剂，并进行了活性测试研究，有望发展出抗高血压新药；发展了通过水相反应、微波合成、有机小分子催化等绿色合成技术合成含氮化合物的新方法，将这些方法用于药物合成，实现了对绿色兽药盐酸沃林妙尼、抗疟药物磷酸哌喹和盐酸阿莫地喹、降血脂药物苯氟雷斯（Benfluorex）和拟钙剂Mimpara的合成工艺改进，有望发展出经济实用、绿色环保并适用于规模化生产的新工艺。

　　运用现代分子生物学与分子细胞生物学等多学科研究手段，从分子、细胞、动物个体水平上深入研究Wnt信号通路蛋白抗拮剂的抗癌药效及其分子机制，从而为癌症的预防与临床治疗提供新的分子靶向治疗策略。与此同时，筛选并设计合成具有抗癌活性的小分子化合物。

♦ 近期代表研究论文 

1.　P. Wu, Z. Wang, M. Cheng, L. Zhou, J. Sun*, “Development of Highly Enantioselective New Lewis Basic N-Formamide Organocatalysts for Hydrosilylation of Imines with an Unprecedented Substrate Profile”, Tetrahedron 2008, 64, 11304-11312.

2.　C. Wang, X. Wu, L. Zhou, J. Sun*, “A Highly Enantioselective Organocatalytic Method for Reduction of Aromatic N-Alkyl Ketimines”, Chem. Eur. J. 2008, 14, 8789-8792. 

3.　D. Pei, Y. Zhang. S. Wei, M. Wang, J. Sun*, “Rationally-Designed S-Chiral Bissulfinamides as Highly Enantioselective Organocatalysts for Reduction of Ketimines”, Adv. Synth. Catal. 2008, 350, 619-623. 该论文被Benjamin List在SYNFACTS 2008, 5, 0531撰文专题正面评述.

4.　L. Zhou, Z. Wang, S. Wei, J. Sun*, “Evolution of Chiral Lewis Basic N-Formamide as Highly Effective Organocatalyst for Asymmetric Reduction of Both Ketones and Ketimines with an Unprecedented Substrate Scope”, Chem. Commun. 2007, 2977 - 2979. 该论文被Nature China专题报道并作为亮点介绍.

5.　Z. Wang, S. Wei, C. Wang, J. Sun*, “Enantioselective Hydrosilylation of Ketimines Catalyzed by Lewis Basic C2-Symmetric Chiral Tetraamide”, Tetrahedron: Asymmetry 2007, 18, 705-709.

6.　D. Pei, Z. Wang, S. Wei, Y. Zhang, J. Sun*, “S-Chiral Sulfinamides as Highly Enantioselective Organocatalysts”, Org. Lett. 2006, 8(25), 5913-5915. 该论文被Benjamin List在SYNFACTS 2008, 5, 0531撰文专题正面评述. 

7.　Z. Wang, M. Cheng, P. Wu, S. Wei, J. Sun*, “L-Piperazine-2-Carboxylic Acid Derived N-Formamide as Highly Enantioselective Lewis Basic Catalyst for Hydrosilylation of N-Aryl Imines with an Unprecedented Substrate Profile”, Org. Lett. 2006, 8(14), 3045-3048. 该论文被Organic Chemistry Portal收录（www.organic-chemistry.org/abstracts/lit1/316.shtm）.

8.　Z. Wang, X. Ye, S. Wei, P. Wu, A. Zhang, J. Sun*, “A Highly Enantioselective Lewis Basic Organocatalyst for Reduction of N-Aryl Imines with Unprecedented Substrate Spectrum”, Org. Lett. 2006, 8(5), 999-1001. 该论文被Organic Chemistry Portal收录（www.organic-chemistry.org/abstracts/lit1/183.shtm）.

9.　C. Cheng, J. Sun*, C. Wang, Y. Zhang, S. Wei, F. Jiang, Y. Wu, “Protonated N’-benzyl-N’-prolyl Proline Hydrazide as Highly Enantioselective Catalyst for Direct Asymmetric Aldol Reaction”, Chem. Commun. 2006, (2), 215 - 217.

10.　  X. Z. Guo, L. Shi, R.Wang, X. X. Liu, B. G. Li, X. X. Lu* “Synthesis and biological activities of novel nonpeptide angiotensin II receptor antagonists based on benzimidazole derivatives bearing a heterocyclic ring”, Bioorg. Med. Chem. 2008, 16, 10301–10310。 

11.　  T. K. Huang, R. Wang, L. Shi, X. X. Lu*, “Montmorillonite K-10: An efficient and reusable catalyst for the synthesis of quinoxaline derivatives in water”, Catal. Commun., 2008, 9, 1143–1147.

12.　  R. Wang, T. K. Huang, L. Shi, B. G. Li, X. X. Lu*, “Heteropoly Acids Catalyzed Direct Mannich Reactions: Three-Component Synthesis of N-Protected β-Amino Ketones”，Synlett 2007, 2197–2200.

13.　  R. Wang, B. G. Li, T. K. Huang, L. Shi, X. X. Lu*, “NbCl5-Catalyzed One-pot Mannich-type Reaction: Three Component Synthesis of β–Amino Carbonyl Compounds”, Tetrahedron Lett., 2007, 48, 2071–2073.

14.　  R. Wang, X. X. Lu*, X. Q. Yu, L. Shi, Y. Sun, “Acid-Catalyzed Solvent-Free Synthesis of 2-Arylbenzimidazoles under Microwave Irradiation”, J. Mol. Catal. A: Chem., 2007, 266, 198–201.

15.　  Tang Y, Simoneau AR, Liao W, Guo Y, Hoang BH, Hope C, Liu F, Li S, Xie J, Holcombe RF, Jurnak FA, Mercola D, Zi X. WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition of human invasive urinary bladder cancer cells. Molecular Cancer Therapeutics 2009, 8(2): 458–68.

16.　  Tang Y, Simoneau AR, Xie J, Shahandeh B, Zi X. Effects of the Kava Chalcone Flavokawain A Differ in Bladder Cancer Cells with Wild-type versus Mutant p53. Cancer Prevention Research 2008, 1(6):439–51. (Perspectives: Rajesh Agarwal and Gagan Deep. Kava, a Tonic for Relieving the Irrational Development of Natural Preventive Agents. Cancer Prevention Research 2008, 1(6):409-412.)

17.　  Guo Y, Xie J, Rubin E, Tang YX, Lin F, Zi X, Hoang BH. Frzb, a secreted Wnt antagonist, decreases growth and invasiveness of fibrosarcoma cells associated with inhibition of Met signaling. Cancer Research 2008, 68(9):3350-60.