1. Semisynthetic Enzymes for Organic Synthesis 赵峰 2014.3.22 1

2. Introduction HomogeneousEnzymatic Enantiomerseasy accesschallenging Solvent tolerancemostly organicmostly aqueous Substrate scopelargenarrow Optimizationchemicalgenetic Turnover numberlimitedlarge Metals involvedany metallimited (biorelevant) Features of Homogeneous and Enzymatic Catalysis Ward, T. R. Acc. Chem. Res. 2011, 44, 47-57 2

3. Combination——Semisynthetic Enzymes 3

4. Content Artificial Metalloenzymes – Covalent Strategies and applications – Supramolecular Strategies and applications Nonmetal-Containing Systems – Covalent Strategies and applications Conclusion 4

5. Content Artificial Metalloenzymes – Covalent Strategies and applications – Supramolecular Strategies and applications Nonmetal-Containing Systems – Covalent Strategies and applications Conclusion 5

6. General Structure of Artificial Metalloenzymes 6

7. Covalent Anchoring Strategies Lewis, J. C. ACS Catal. 2013, 3, 2954-2975 7

8. Covalent Anchoring Strategies Lewis, J. C. ACS Catal. 2013, 3, 2954-2975 8

9. Representative Cofactors 9

10. Reactions by Covalent Anchoring AME 10 Distefano,M. D. J. Am. Chem. Soc. 1997, 119, 11643-11652

11. Reactions by Covalent Anchoring AME 11 Hilvert, D. Chem. Commun., 2011, 47, 12068–12070

12. 12 Reactions by Covalent Anchoring AME Roelfes, G. Angew. Chem. Int. Ed. 2012, 51, 7472 –7475

13. 13 Reactions by Covalent Anchoring AME Roelfes, G. Chem. Sci., 2013, 4, 3578–3582

14. Content Metal-Containing Systems – Covalent Strategies and applications – Supramolecular Strategies and applications Nonmetal-Containing Systems – Covalent Strategies and applications Conclusion 14

15. Supramolecular Anchoring Strategies 15 Take advantage of the remarkable affinity of biotin for either avidin or streptavidin ！

16. Represetative Biotinylated Cofactors 16

17. Whitesides, G. M. J. Am. Chem. Soc. 1978, 100, 306–307 17 ProteinTON ee% PolarimetricNMR None475<2 Lysozyme450<1<2 CA50<10 BSA150<5 Avidin(1equiv)>5004144 Avidin.biotin200<4 Reactions by AME Bsed on Biotin-Avidin Technology

18. 18 Reactions by AME Bsed on Biotin-Avidin Technology Ward, T. R. J. Am. Chem. Soc. 2003, 125, 9030-9031

19. 19 Reactions by AME Bsed on Biotin-Avidin Technology Ward, T. R. J. Am. Chem. Soc. 2006, 128, 8320-8328

20. 20 Reactions by AME Bsed on Biotin-Avidin Technology Ward, T. R. Angew. Chem. Int. Ed. 2011, 50, 3026 –3029

21. 21 Reactions by AME Bsed on Biotin-Avidin Technology Ward, T. R. Angew. Chem., Int. Ed. 2008, 47, 701–705

22. 22 Reactions by AME Bsed on Biotin-Avidin Technology Ward, T. R. Chem. Commun. 2011, 47, 12065-12067

23. Content Artificial Metalloenzymes – Covalent Strategies and applications – Supramolecular Strategies and applications Nonmetal-Containing Systems – Covalent Strategies and applications Conclusion 23

24. General Structure of Nonmetal- Containing Systems 24

25. Colvalent Anchoring Strategy Jones, J. B. J. Am. Chem. Soc. 1997, 119, 5265-5266 Jones, J. B. Bioorg. med. Chem.. 1999, 7, 1381 25

26. Colvalent Anchoring Strategy Distefano, M. D. J. Am. Chem. Soc., 1996, 118, 10702-10706 Kaiser, E. T. Biochem. Biophys. Res. Commun. 1977, 76, 64-70 Hilvert, D. J. Am. Chem. Soc. 1989, 111, 4513-4514 Suckling, C. J. Bioorg. Med. Chem. 1993, 3, 531-534 26

27. Kaiser, E. T. Biochem. Biophys. Res. Commun. 1977, 76, 64-70 27 Reactions by Nonmetal Artificial Enzymes

28. Suckling, C. J. Bioorg. Med. Chem. 1993, 3, 531-534 28

29. Reactions by Nonmetal Artificial Enzymes Hilvert, D. J. Am. Chem. Soc. 1989, 111, 4513-4514 29

30. Reactions by Nonmetal Artificial Enzymes 30 Distefano, M. D. J. Am. Chem. Soc., 1996, 118, 10702-10706

31. Content Artificial Metalloenzymes – Covalent Strategies and applications – Supramolecular Strategies and applications Nonmetal-Containing Systems – Covalent Strategies and applications Conclusion 31

32. Conclusion A lot of AMEs have been synthesized, and some of them have been successfully applied to organic synthesis. Construction of AMEs can be complicated to get host Protein and guest motif ready for conjunction at the same time The reaction scope is still narrow, and selectivity is not very good Further research work is desired to enlarge the number of AME family and find new applications of them 32

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