Cheng, Wei-Chieh 鄭偉杰






  • B.S., Chemistry, National Cheng-Kung University Taiwan, 1991
  • M.S., Chemistry National Tsing-Hua University Taiwan, 1993
  • Ph.D., Chemistry, University of California, Davis CA, USA, 1997-2002
  • Postdoctoral Fellow, the Scripps Research Institute, USA, 2002-2004
  • Assistant Professor, Genomics Research Center, Academia Sinica, Taiwan, 2004-2010
  • Associate Professor, Genomics Research Center, Academia Sinica, Taiwan, 2010-present


  • Skaggs Postdoctoral Fellowship, 2002-2004
  • The distinguished lectureship award (Natural products synthesis), the CSJ (Chemical Society of Japan) Asian International Symposium, Japan, 2007


The major research efforts of this group are directed toward the development of new synthetic strategies for biologically interesting natural products and heterocyclics. To understand the relationships between small molecules and biological systems, combinatorial approaches are applied in our diverse molecule library synthesis (core diversity, substituent diversity, and configuration diversity) with the assistance of automated or semi-automated equipment.

  • Organic Chemistry and Chemical Biology
  • Development of new synthetic methodology
  • Natural product and natural product-like molecule synthesis
  • Synthesis of biologically interesting molecule libraries
  • Development of new high-throughput library synthesis
  • Combinatorial approach towards the synthesis of natural product-like or novel heterocyclic molecule libraries
  • Study of the cell wall transglycosylase as a potential antibacterial target
  • Lead discovery of cell wall synthesis enzymes in mycobacterium
  • Novel chemical probe synthesis and application
  • Synthesis of chemical chaperones towards lysosomal storage disease associated enzymes
  • Synthesis of novel five- and six-membered iminosugars


同時也根據理論設計與組合式化學的合成方法,將包括雜環、非天然之氨基酸 (胜肽)、lysophosphatidic acid衍生物以及iminocyclotals等之新穎的小分子設計並合成為抑制劑或抗頡劑(agonists),以與疾病有關的酵素或受體 (receptors)為標的,研究其結構與活性之間的關係(SARs)。

由於近來在小分子組合式化學的研究日趨活絡,因此固相有機合成(SPOS)方面的應用與研究也受到高度關注。在此領域裡,我們的興趣在於新功能化樹 脂開發、linker開發(尤其是traceless linkers)、化學轉換、SPOS裂解策略,以及利用新方法來更有效率地建置小分子資料庫以供生化篩選使用。


  • Jan JT, Cheng TR, Juang YP, Ma HH, Wu YT, Yang WB, Cheng CW, Chen X, Chou TH, Shie JJ, Cheng WC, Chein RJ, Mao SS, Liang PH, Ma C, Hung SC, Wong CH, 2021, “Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection.”, Proceedings of the National Academy of Sciences of the United States of America, 118 (5), e2021579118. (SCIE)
  • Cheng Wei‐Chieh, You Ting‐Yun, Teo Zhen‐Zhuo, Sayyad Ashik A., Maharana Jitendra, Guo Chih‐Wei, Liang Pi‐Hui, Lin Chung‐Shun, Meng Fan‐Chun, 2020, “Further Insights on Structural Modifications of Muramyl Dipeptides to Study the Human NOD2 Stimulating Activity”, Chemistry – An Asian Journal, 15(22), 3836-3844.
  • Cheng WC, Liu WJ, Hu KH, Tan YL, Lin YT, Chen WA, Lo LC, 2020, “Rapid Synthesis of a Natural Product-Inspired Uridine Containing Library.”, ACS combinatorial science, 22(11), 600-607. (SCIE)
  • Chen Wei‐An, Sayyad Ashik, Chen Chiao‐Wen, Chen Yu‐Hsin, Cheng Ting‐Jen R., Cheng Wei‐Chieh, 2019, “Divergent Synthesis of Bicyclic Iminosugars: Preparation of (−)‐Swainsonine‐Based Alkaloids and Their Inhibition Study towards α ‐Human Mannosidases”, Asian Journal of Organic Chemistry, 8(12), 2233-2242. (SCIE)
  • Cheng WC, Lin CK, Li HY, Chang YC, Lu SJ, Chen YS, Chang SY, 2018, “A combinatorial approach towards the synthesis of non-hydrolysable triazole-iduronic acid hybrid inhibitors of human alpha-l-iduronidase: discovery of enzyme stabilizers for the potential treatment of MPSI.”, CHEMICAL COMMUNICATIONS, 54(21), 2647-2650. (SCIE)
  • Li HY, Lee JD, Chen CW, Sun YC, Cheng WC, 2018, “Synthesis of (3S,4S,5S)-trihydroxylpiperidine derivatives as enzyme stabilizers to improve therapeutic enzyme activity in Fabry patient cell lines.”, European journal of medicinal chemistry, 144, 626-634. (SCIE)
  • Chen KT, Lin CK, Guo CW, Chang YF, Hu CM, Lin HH, Lai Y, Cheng TR, Cheng WC, 2017, “Effect of the lipid II sugar moiety on bacterial transglycosylase: the 4-hydroxy epimer of lipid II is a TGase inhibitor.”, CHEMICAL COMMUNICATIONS, 53(4), 771-774. (SCIE)
  • Cheng WC, Wang JH, Yun WY, Li HY, Hu JM, 2017, “Rapid preparation of (3R,4S,5R) polyhydroxylated pyrrolidine-based libraries to discover a pharmacological chaperone for treatment of Fabry disease.”, European journal of medicinal chemistry, 126, 1-6. (SCIE)
  • Lin CK, Yun WY, Lin LT, Cheng WC, 2016, “A concise approach to the synthesis of the unique N-mannosyl d-beta-hydroxyenduracididine moiety in the mannopeptimycin series of natural products.”, Organic & biomolecular chemistry, 14(17), 4054-4060. (SCIE)
  • Cheng WC, Wang JH, Li HY, Lu SJ, Hu JM, Yun WY, Chiu CH, Yang WB, Chien YH, Hwu WL, 2016, “Bioevaluation of sixteen ADMDP stereoisomers toward alpha-galactosidase A: Development of a new pharmacological chaperone for the treatment of Fabry disease and potential enhancement of enzyme replacement therapy efficiency.”, European journal of medicinal chemistry, 123, 14-20. (SCIE)
  • Lin CK, Hou CC, Guo YY, Cheng WC, 2016, “Design and Synthesis of Orthogonally Protected d- and l-beta-Hydroxyenduracididines from d-lyxono-1,4-Lactone.”, Organic letters, 18(20), 5216-5219. (SCIE)
  • Chen KT, Chen PT, Lin CK, Huang LY, Hu CM, Chang YF, Hsu HT, Cheng TJ, Wu YT, Cheng WC, 2016, “Structural Investigation of Park's Nucleotide on Bacterial Translocase MraY: Discovery of Unexpected MraY Inhibitors.”, Scientific reports, 6, 31579. (SCIE)
  • Zuegg J, Muldoon C, Adamson G, McKeveney D, Le Thanh G, Premraj R, Becker B, Cheng M, Elliott AG, Huang JX, Butler MS, Bajaj M, Seifert J, Singh L, Galley NF, Roper DI, Lloyd AJ, Dowson CG, Cheng TJ, Cheng WC, Demon D, Meyer E, Meutermans W, Cooper MA, 2015, “Carbohydrate scaffolds as glycosyltransferase inhibitors with in vivo antibacterial activity.”, Nature communications, 6, 7719. (SCIE)
  • Chen PT, Lin CK, Tsai CJ, Huang DY, Nien FY, Lin WW, Cheng WC, 2015, “Expeditious Synthesis of Enantiopure, Orthogonally Protected Bis-alpha-Amino Acids (OPBAAs) and their Use in a Study of Nod1 Stimulation.”, Chemistry-An Asian Journal, 10(2), 474-482. (SCIE)
  • Cheng WC, Guo CW, Lin CK, Jiang YR, 2015, “Synthesis and Inhibition Study of Bicyclic Iminosugar-​Based Alkaloids, Scaffolds, and Libraries towards Glucosidase”, Israel Journal of Chemistry, 55(3-4), 403-411. (SCIE)
  • Lin CK, Chen KT, Hu CM, Yun WY, Cheng WC, 2015, “Synthesis of 1-C-Glycoside-Linked Lipid II Analogues Toward Bacterial Transglycosylase Inhibition.”, Chemistry-A European Journal, 21(20), 7511-7519. (SCIE)
  • Chen KT, Huang DY, Chiu CH, Lin WW, Liang PH, Cheng WC, 2015, “Synthesis of Diverse N-Substituted Muramyl Dipeptide Derivatives and Their Use in a Study of Human NOD2 Stimulation Activity.”, Chemistry-A European Journal, 21(34), 11984-11988. (SCIE)
  • Lin CK, Cheng LW, Li HY, Yun WY, Cheng WC, 2015, “Synthesis of novel polyhydroxylated pyrrolidine-triazole/-isoxazole hybrid molecules.”, Organic & biomolecular chemistry, 13(7), 2100-2107. (SCIE)
  • Tseng YY, Liou JM, Hsu TL, Cheng WC, Wu MS, Wong CH, 2014, “Development of bacterial transglycosylase inhibitors as new antibiotics: moenomycin A treatment for drug-resistant Helicobacter pylori.”, Bioorganic & medicinal chemistry letters, 24(11), 2412-2414. (SCIE)
  • Huang LY, Huang SH, Chang YC, Cheng WC, Cheng TJ, Wong CH, 2014, “Enzymatic Synthesis of Lipid II and Analogues.”, Angewandte Chemie-International Edition, 53(31), 8060-8065. (SCIE)
  • Hsu CH, Schelwies M, Enck S, Huang LY, Huang SH, Chang YF, Cheng TJ, Cheng WC, Wong CH, 2014, “Iminosugar C-Glycoside Analogues of alpha-d-GlcNAc-1-Phosphate: Synthesis and Bacterial Transglycosylase Inhibition.”, The Journal of organic chemistry, 79(18), 8629-8637. (SCIE)
  • Cheng TJ, Chan TH, Tsou EL, Chang SY, Yun WY, Yang PJ, Wu YT, Cheng WC, 2013, “From Natural Product-Inspired Pyrrolidine Scaffolds to the Development of New Human Golgi alpha-Mannosidase II Inhibitors.”, Chemistry-An Asian Journal, 8(11), 2600-2604. (SCIE)
  • Huang SH, Wu WS, Huang LY, Huang WF, Fu WC, Chen PT, Fang JM, Cheng WC, Cheng TJ, Wong CH, 2013, “New continuous fluorometric assay for bacterial transglycosylase using Forster resonance energy transfer.”, Journal of the American Chemical Society, 135(45), 17078-17089. (SCIE)
  • Cheng WC, Weng CY, Yun WY, Chang SY, Lin YC, Tsai FJ, Huang FY, Chen YR, 2013, “Rapid modifications of N-substitution in iminosugars: development of new beta-glucocerebrosidase inhibitors and pharmacological chaperones for Gaucher disease.”, Bioorganic & medicinal chemistry, 21(17), 5021-5028. (SCIE)
  • Chen KT, Kuan YC, Fu WC, Liang PH, Cheng TJ, Wong CH, Cheng WC, 2013, “Rapid preparation of mycobacterium N-glycolyl Lipid I and Lipid II derivatives: a biocatalytic approach.”, Chemistry-a European Journal, 19(3), 834-838. (SCIE)
  • Pan YW, Guo CW, Tu HY, Tsai CW, Cheng WC, 2013, “Solid-Phase Synthesis of Diverse Spiroisoxazolinodiketopiperazines.”, ACS combinatorial science, 15(8), 425-434. (SCIE)
  • Hao-Wei Shih, Kuo-Ting Chen, Wei-Chieh Cheng*, 2012, “One-pot synthesis of phosphate diesters and phosphonate monoesters via a combination of microwave-CCl3CN-pyridine coupling conditions”, Tetrahedron Lett., 53(2), 243-246. (SCIE)
  • Huang CY, Shih HW, Lin LY, Tien YW, Cheng TJ, Cheng WC, Wong CH, Ma C, 2012, “Crystal structure of Staphylococcus aureus transglycosylase in complex with a lipid II analog and elucidation of peptidoglycan synthesis mechanism.”, Proceedings of the National Academy of Sciences of the United States of America, 109(17), 6496-6501. (SCIE)
  • Shih HW, Chang YF, Li WJ, Meng FC, Huang CY, Ma C, Cheng TJ, Wong CH, Cheng WC, 2012, “Effect of the Peptide Moiety of Lipid II on Bacterial Transglycosylase.”, Angewandte Chemie-International Edition, 51(40), 10123-10126. (SCIE)
  • Hsu YC, Chen NC, Chen PC, Wang CC, Cheng WC, Wu HN, 2012, “Identification of a small-molecule inhibitor of dengue virus using a replicon system.”, Archives of virology, 157(4), 681-688. (SCIE)
  • Shih HW, Chen KT, Cheng TJ, Wong CH, Cheng WC, 2011, “A New Synthetic Approach toward Bacterial Transglycosylase Substrates, Lipid II and Lipid IV.”, Org. Lett., 13(17), 4600-4603. (SCIE)
  • Chang YF, Guo CW, Chan TH, Pan YW, Tsou EL, Cheng WC, 2011, “Parallel synthesis of natural product-like polyhydroxylated pyrrolidine and piperidine alkaloids.”, Molecular diversity, 15(1), 203-214. (SCIE)
  • Meng FC, Chen KT, Huang LY, Shih HW, Chang HH, Nien FY, Liang PH, Cheng TJ, Wong CH, Cheng WC, 2011, “Total Synthesis of Polyprenyl N-Glycolyl Lipid II as a Mycobacterial Transglycosylase Substrate.”, Org. Lett., 13(19), 5306-5309. (SCIE)
  • Tin-Hao Chan, Yi-Fan Chang, Jung-Jung Hsu, and Wei-Chieh Cheng, 2010, “Straightforward Synthesis of Diverse 1-Deoxyazapyranosides via Stereocontrolled Nucleophilic Additons to Six-Membered Cyclic Nitrones”, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2010(59), 5555-5559. (SCIE)
  • Chen-Yu Liu, Chih-Wei Guo, Yi-Fan Chang, Jen-Tsung Wang, Hao-Wei Shih, Yu-Fang Hsu, Chia-Wei Chen, Shao-Kang Chen, Yen-Chih Wang, Ting-Jen R. Cheng, Che Ma, Chi-Huey Wong, Jim-Min Fang* and Wei-Chieh Cheng*, 2010, “Synthesis and Evaluation of a New Fluorescent Transglycosylase Substrate: Lipid II-Based Molecule Possessing a Dansyl-C20 Polyprenyl Moiety”, Org. Lett., 12(7), 1608-1611.. (SCIE)
  • Shih HW, Chen KT, Chen SK, Huang CY, Cheng TJ, Ma C, Wong CH, Cheng WC, 2010, “Combinatorial approach toward synthesis of small molecule libraries as bacterial transglycosylase inhibitors.”, Organic & biomolecular chemistry, 8(11), 2586-2593. (SCIE)
  • Cheng TJ, Wu YT, Yang ST, Lo KH, Chen SK, Chen YH, Huang WI, Yuan CH, Guo CW, Huang LY, Chen KT, Shih HW, Cheng YS, Cheng WC, Wong CH, 2010, “High-throughput identification of antibacterials against methicillin-resistant Staphylococcus aureus (MRSA) and the transglycosylase.”, Bioorganic & medicinal chemistry, 18(24), 8512-8529. (SCIE)
  • Su CY, Cheng TJ, Lin MI, Wang SY, Huang WI, Lin-Chu SY, Chen YH, Wu CY, Lai MM, Cheng WC, Wu YT, Tsai MD, Cheng YS, Wong CH, 2010, “High-throughput identification of compounds targeting influenza RNA-dependent RNA polymerase activity.”, Proceedings of the National Academy of Sciences of the United States of America, 107(45), 19151-19156. (SCIE)
  • Sung, M. T. Lai, Y. T. Huang, C. Y. Chou, L. Y. Shih, H. W. Cheng, W. C. Wong, C. H. Ma, C., 2009, “Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli”, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106(22), 8824-8829. (SCIE)
  • Tsou, En-Lun, Yeh, Yao-Ting, Liang, Pi-Hui, Cheng, Wei-Chieh*, 2009, “A convenient approach toward the synthesis of enantiopure isomers of DMDP and ADMDP”, Tetrahedron, 65(1), 93-100. (SCIE)
  • Shih, Hao-Wei, Guo, Chih-Wei, Lo, Kien-Hock, Huang, Min-Yang, Cheng, Wei-Chieh*, 2009, “Solution-Phase Parallel Synthesis of Novel Spirooxazolinoisoxazolines”, Journal of Combinatorial Chemistry, 11(2), 281-287.
  • Shirley, Morgan E., Cheng, Wei-Chieh, 2008, “Synthesis of new polyhydroxylated pyrrolidine alkaloids and their future as biological inhibitors”, MEDI-306 pages, paper presented at 235th ACS National Meeting, New Orleans, LA, United States, Department of Biochemistry, IREU,Texas A&M,Overland Park,KS,USA.: Department of Biochemistry, IREU,Texas A&M,Overland Park,KS,USA., 2008-04-06 ~ 2008-04-10.
  • Cheng TJ, Sung MT, Liao HY, Chang YF, Chen CW, Huang CY, Chou LY, Wu YD, Chen YH, Cheng YS, Wong CH, Ma C, Cheng WC, 2008, “Domain requirement of moenomycin binding to bifunctional transglycosylases and development of high-throughput discovery of antibiotics.”, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 105(2), 431-6. (SCIE)
  • Chang, Yi-Fan, Liu, Chen-Yu, Guo, Chih-Wei, Wang, Yen-Chih, Fang, Jim-Min, Cheng, Wei-Chieh*, 2008, “Solid-Phase Organic Synthesis of Polyisoprenoid Alcohols with Traceless Sulfone Linker”, J. Org. Chem., 73(18), 7197-7203. (SCIE)
  • Shih, Hao-Wei, Cheng, Wei-Chieh*, 2008, “Solution-phase parallel synthesis of highly diverse spiroisoxazolinohydantoins”, Tetrahedron Lett., 49(6), 1008-1011. (SCIE)
  • Huang, Chih-Ming, Liu, Rai-Shung, Wu, Tian-Shung, Cheng, Wei-Chieh*, 2008, “Structural establishment of polygalatenosides A and B by total synthesis”, Tetrahedron Lett., 49(18), 2895-2898. (SCIE)
  • Tsou EL, Chen SY, Yang MH, Wang SC, Cheng TR, Cheng WC, 2008, “Synthesis and biological evaluation of a 2-aryl polyhydroxylated pyrrolidine alkaloid-based library.”, Bioorganic & medicinal chemistry, 16(24), 10198-204. (SCIE)
  • Chang, Yi-Fan, Jiang, Yi-Rui, Cheng, Wei-Chieh*, 2008, “Traceless sulfone linker cleavage triggered by ozonolysis: solid-phase synthesis of diverse alpha -beta -unsaturated carbonyl compounds”, Tetrahedron Lett., 49(3), 543-547.. (SCIE)
  • Sanna MG, Wang SK, Gonzalez-Cabrera PJ, Don A, Marsolais D, Matheu MP, Wei SH, Parker I, Jo E, Cheng WC, Cahalan MD, Wong CH, Rosen H, 2006, “Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P1 antagonist in vivo.”, Nature chemical biology, 2(8), 434-41. (SCIE)
  • P. H. Liang, W. C. Cheng, Y. L. Lee, H. P. Yu, Y. T. Wu, Y. L. Lin and C. H. Wong, 2006, “Novel five-membered iminocyclitol derivatives as selective and potent glycosidase inhibitors: new structures for antivirals and osteoarthritis”, Chembiochem, 7, 165-173. (SCIE)
  • Sawkar AR, Adamski-Werner SL, Cheng WC, Wong CH, Beutler E, Zimmer KP, Kelly JW, 2005, “Gaucher disease-associated glucocerebrosidases show mutation-dependent chemical chaperoning profiles.”, Chemistry & biology, 12(11), 1235-44.
  • M. D. Best, A. Brik, E. Chapman, L. V. Lee, W. C. Cheng and C. H. Wong, 2004, “Rapid discovery of potent sulfotransferase inhibitors by diversity-oriented reaction in microplates followed by in situ screening”, Chembiochem, 5, 811-819. (SCIE)
  • W. C. Cheng, 2003, “The sulfone linker in solid-phase organic synthesis: development of cleavage strategies for the preparation of small molecules”, ASSAY DRUG DEV TECHNOL, 1, 217. (SCIE)
  • W. C. Cheng , M. J. Kurth, 2002, “The Zincke reaction. A review”, Organic Preparations and Procedures International, 34(6), 585-608. (SCIE)
  • A. R. Sawkar, W. C. Cheng, E. Beutler, C. H. Wong, W. E. Balch and J. W. Kelly, 2002, “Chemical chaperones increase the cellular activity of N370S beta -glucosidase: a therapeutic strategy for Gaucher disease”, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 99, 15428-15433. (SCIE)
  • W. C. Cheng, C. C. Lin and M. J. Kurth, 2002, “Dimsyl anion in the monoalkylation of solid-phase alkyl sulfones”, Tetrahedron Lett, 43, 2967-2970. (SCIE)
  • W. C. Cheng, M. Wong, M. M. Olmstead and M. J. Kurth, 2002, “Solid-phase synthesis of novel isoxazolocyclobutanones and isoxazolinocyclobutenones”, Org Lett, 4, 741-744. (SCIE)
  • W. C. Cheng, Y. Liu, M. Wong, M. M. Olmstead, K. S. Lam and M. J. Kurth, 2002, “Stereoselective synthesis of unnatural spiroisoxazolinoproline-based amino acids and derivatives”, J Org Chem, 67, 5673-5677. (SCIE)
  • W. C. Cheng , M. J. Kurth, 2002, “The sulfone linker in solid-phase synthesis: preparation of 3,5-disubstituted cyclopent-2-enones”, J Org Chem, 67, 4387-4391. (SCIE)
  • W. C. Cheng, M. M. Olmstead and M. J. Kurth, 2001, “Vinyl sulfones in solid-phase synthesis: preparation of 4,5,6,7-tetrahydroisoindole derivatives”, J Org Chem, 66, 5528-5533. (SCIE)
  • W. C. Cheng, C. Halm, J. B. Evarts, M. M. Olmstead and M. J. Kurth, 1999, “Allylic sulfones in solid-phase synthesis: Preparation of cyclobutylidenes”, J Org Chem, 64, 8557-8562. (SCIE)