1) 基于全合成的活性天然产物结构改造与优化；即以全合成为手段、结合药物分子设计的基本原理与方法，对结构比较复杂、但具有显著药物开发前景的天然产物进行有目的的深度结构修饰，以期获得药效更强、毒副作用更小、理化性质更优、更易于实现规模化制备的天然产物类似物。目前该课题主要涉及苯(醌)安莎霉素(如格尔德霉素)和氨基香豆素(如新生霉素)两类天然产物。

2) 以热休克蛋白90 (Heat Shock Protein 90, Hsp90)为作用靶点的新型抗肿瘤药物研究。以课题组前期发现的杂环类小分子Hsp90抑制剂为先导化合物，运用计算机辅助设计方法，进行系统的构效关系探讨和全面的结构优化研究，以期获得具有显著临床应用前景的药物候选物。 

论文

1.        Jin L , Zhang R , Zhang Z , et al. Totalsynthesis based modification of Benzoquinone Ansamycin Antibiotics: C8Diversification of C5-C15 Fragments[J]. Tetrahedron Letters, 2019.

2.        Zhang Z , Xue N , Bian C , et al.C15-methoxyphenylated 18-deoxy-herbimycin A analogues, their in vitroanticancer activity and heat shock protein 90 binding affinity[J]. Bioorganic& Medicinal Chemistry Letters, 2016:4287-4291.

3.        Xu M Y , Xue N N , Liu D , et al.4,5,6,7-Tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine as a new scaffold for heatshock protein 90 inhibitors[J]. 中国化学快报(英文版),2016.

4.        李永强,严睿, 卞传才,等.Practical Synthesis of the C(11)~C(21) Fragment of Geldanamycin[J]. 有机化学,2014, 000(010):2035-2039.

5.        Li W , Li Y , Yu X . Synthesis ofOxazolidinone Derivative from Chloramphenicol and Its Asymmetric Induction inAldol Reaction[J]. Chinese Journal of Organic Chemistry, 2015, 35(8):1657-1664.

6.        张智,靳龙, 俞晓明.安莎霉素类天然产物的结构改造[C]// 第一届药学学报药学前沿论坛暨2015年中国药学会中药与天然药物专业委员会会议论文摘要集.0.

7.        M. Xu, N. Xue, D. Liu, Y. Zhou, W. Li, Y. Li, X. Chen, X. Yu,4,5,6,7-Tetrahydro -[1,2,3]triazolo[1,5-a]pyrazine as a new scaffold for heatshock protein 90 inhibitors, Manuscript in preparation.

8.        李永强，严睿，卞传才，张智，刘迪，俞晓明*；格尔德霉素C(11)-C(21)片段的合成；有机化学(Chin. J. Org. Chem.)2014, 34, 2035-2039.

9.        R. Yan, C. Bian, X. Yu, Total synthesis of herbimycin A, Org.Lett. 2014, 16, 3280−3283.

10.    C. Bian, R. Yan, X. Yu, Total synthesis of reblastatin: convenientpreparation of coupling partners and scaled assembly, Tetrahedron 70,2982-2991 (2014).

11.    D. Liu, X. Yu, L. Huang, Novel Concise Synthesis of(−)-Clausenamide, Chin. J. Chem. 31, 344-8 (2013).

12.    L. Zhang, Y. Zhou, X. Yu, Suzuki-Miyaura coupling basedenantioselective synthesis of epi-clausemamide and enantiomer of its 3-deoxyanalogue. Synlett 23, 1217-20 (2012).

13.    D. Liu, X. Yu, Ireland-Claisen rearrangement of secondary allyacetate revisited: inevitable C-silylation circumvented by one-pot applicationof excessive LDA/TMSCl and TBAF. Tetrahed. Lett. 53, 2177-80(2012).

14.    J. Luo, X. Yu, Concise and divergent approach to 3-O-acyl-L-noviosederivatives and their 3-amino bioisosteres: 3-O-benzoyl-L-noviose andN-benzoyl-3-amino-L -noviose. Tetrahed. Lett. 52, 2450 (2011).

15.    J. J. Xue, X. M. Yu, Synthesis of 3- and 6-des-phenyl(-)-clausenamide and alternative synthesis of (+)-epi-clausenamide, Chin.Chem. Lett. 22, 1261 (2011).

16.    J. J. Xue, X. M. Yu, Selective 3- and 6-OH modification of(-)-clausenamide, Chin. Chem. Lett. 22, 761 (2011).

17.    Y.-q. He, Y.-q. Li, L. Ma, X.-M. Yu, Synthesis of 4-des-hydroxylclorobiocin analogues as possible bacterial DNA gyrase B and human Hsp90inhibitors, J. Chin. Pharm. Sci. 20, 218 (2011).

18.    Y. He, J. Xue, Y. Zhou, J. Yang, X. Yu, Selective hydroxylprotection of (+)-noviose via improved synthesis, Tetrahed. Lett. 50,2317 (2009).

19.    李永强，袁霞，周玉美，罗志刚，陈晓光，俞晓明，热休克蛋白90 (Hsp90) 抑制剂荧光标记探针化合物的设计与合成,中国药物化学杂志 19, 170 (2009).

20.    Yu, X. M.; Shen, G.; Neckers, L. M.; Holzbeierlein, J.; Blagg, B.S. J.，Hsp90 Inhibitors Identified from a Library of Novobiocin Analogues. J.Am. Chem. Soc. 127, 12778 (2005). (ACS hot paper)

21.    X. M. Yu, Huijong Han, and Brian S. J. Blagg, Synthesis of Mono-and Dihydroxylated Furanoses, Pyranoses, and an Oxepanose for the Preparationof Natural Product Analogue Libraries. J. Org. Chem. 70, 5599(2005).

22.    X. M. Yu, G. Shen, B. S. J. Blagg, Synthesis of (-)-noviose from2,3-O-Isopropylidene -D-erythronolactol. J. Org. Chem. 69, 7375(2004).

23.    G. Shen, X. M. Yu, B. S. J. Blagg, Synthesis of photolabilenovobiocin analogues. Bioorg. & Med. Chem. Lett. 14, 5903(2004).

24.    B. WANG, X. M. Yu and G.-q. Lin, The first total synthesis ofsphingofungin E and the determination of its stereochemistry. Synlett904 (2001).

25.    X. M. Yu, S. Z. Chen and L. Huang, Studies on the total synthesisof hainanolide (VI)-The first access to the lactone function. Chin. Chem.Lett. 11, 295 (2000).

26.    T. B. HUNAG, X. M. Yu, L. F. LIU and K. WANG, The synthesis andreaction of heterocyclic thiophosphoryl chlorides with ALCl3 or CF3SO3Ag.Phosphorus, Sulfur and Silicon 156, 9 (2000).

27.    X. M. Yu, L. Y. Zhang, S. Z. Chen and L. Huang, Studies on thetotal synthesis of hainanolide (V)-oxidation of the tricyclic olefines withsinglet oxigen. Chin. Chem. Lett. 10 , 657 (1999).

28.    T. B. Huang, K. Wang, X. M. Yu and L. F. Liu, Molecular Structureof 1-diisopropylamino-2-(p-methylphenyl)-3-methylphosph-etane 1-oxide. JiegouHuaxue 17, 329 (1998).

29.    W. Q. YANG, X. M. Yu, S. Z. Chen and L. Huang, Studies on the totalsynthesis of hainanolide (IV)- revising the stereo-chemistry of C2a-H.Chin. Chem. Lett. 8, 1043 (1997).

30.    T. B. Huang, L. F. Liu, X. M. Yu, W. Q. Yang, X. H. Qian and J. L.Zhang, Reaction of Shiff Base of Thiohydrazides with P(NR2)3.Phosphorus, Sulfur and Silicon 122, 307 (1997).

31.    T. B. Huang, L. F. Liu, W. Q. Yang, X. M. Yu, W. Q. Yang, X. H.Qian and J. L. Zhang,Synthesis of Derivatives of [2,3,4]-thiadiazolo[3,2-c]-1,2,3-trihydro[1,3,5,2]- thia- diazaphosphorins. Phosphorus, Sulfur and Silicon 122,299 (1997).

专利

1.        俞晓明，陈晓光，刘迪，吕春婉，李永强，周玉美，马良；三唑并吡嗪（酮）以及异噁唑并哌啶酮类化合物，申请号：201210250715.3 ( 2012)。