Semisynthetic Enzymes for Organic Synthesis 赵峰

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,

Combination——Semisynthetic Enzymes 3

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

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

General Structure of Artificial Metalloenzymes 6

Covalent Anchoring Strategies Lewis, J. C. ACS Catal. 2013, 3,

Covalent Anchoring Strategies Lewis, J. C. ACS Catal. 2013, 3,

Representative Cofactors 9

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

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

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

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

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

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

Represetative Biotinylated Cofactors 16

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

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

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

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

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

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

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

General Structure of Nonmetal- Containing Systems 24

Colvalent Anchoring Strategy Jones, J. B. J. Am. Chem. Soc. 1997, 119, Jones, J. B. Bioorg. med. Chem , 7,

Colvalent Anchoring Strategy Distefano, M. D. J. Am. Chem. Soc., 1996, 118, Kaiser, E. T. Biochem. Biophys. Res. Commun. 1977, 76, Hilvert, D. J. Am. Chem. Soc. 1989, 111, Suckling, C. J. Bioorg. Med. Chem. 1993, 3,

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

Suckling, C. J. Bioorg. Med. Chem. 1993, 3,

Reactions by Nonmetal Artificial Enzymes Hilvert, D. J. Am. Chem. Soc. 1989, 111,

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

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

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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