1. Dihydrophenanthridine: A New and Easily Regenerable NAD(P)H Model for Biomimetic Asymmetric Hydrogenation Chen, Q.-A.; Gao, K.; Duan, Y.; Ye, Z.-S.; Shi, L.; Yang, Y.; Zhou, Y.-G. J. Am. Chem. Soc. 2012, 134, 2442-2448 October 16, 2012

2. Dihydrophenanthridine: A New and Easily Regenerable NAD(P)H Model for Biomimetic Asymmetric Hydrogenation Chen, Q.-A.; Gao, K.; Duan, Y.; Ye, Z.-S.; Shi, L.; Yang, Y.; Zhou, Y.-G. J. Am. Chem. Soc. 2012, 134, 2442-2448 October 16, 2012

3. 3 Background: NADH and NADPH in Living Cells Coenzyme found in living cells. NADPH: anabolic pathways such as lipid synthesis, cholesterol synthesis and fatty acid chain elongation. (Reductive biosynthesis) NADH: coenzyme for oxidoreductases; citric acid cycle; catabolism; fatty acid oxidation; glycolysis (geneation of ATP)

4. 4 Background: NADH and NADPH in Living Cells Anaerobic Conditions

5. 5 Glyceraldehyde-3-phosphate Dehydrogenase

6. 6 Fatty Acid Biosynthesis How good hydride donors are NADH and NADPH?

7. 7 Relative Hydride Donor Ability of HEH Mayr, H.; Bug, T.; Gotta, M. F.; Hering, N.; Irrgang, B.; Janker, B.; Kempf, B.; Loos, R.; Ofial, A. R.; Remennikov, G.; Schimmel, H. J. Am. Chem. Soc. 2001, 123, 9500.

8. 8 Relative Hydride Donor Ability of HEH Richter, D.; Mayr, H. Angew. Chem. Int. Ed. 2009, 48, 1958.

9. 9 Relative Hydride Donor Ability of HEH

10. 10 Background: HEH As an Organic Reagent Mayer, S.; List, B. Angew. Chem. Int. Ed. 2006, 45, 4193.

11. 11 Background: HEH As an Organic Reagent Rueping, M.; Antonchick, A. P.; Theissmann, T. Angew. Chem. Int. Ed. 2006, 45, 6751.

12. 12 Background: HEH as an Organic Catalyst Will reduce pyridine without reducing the imine Regioselectivity of the reduction

13. 13 Background: HEH as an Organic Catalyst Chen, Q. A.; Chen, M. W.; Yu, C. B.; Shi, L.; Wang, D. S.; Yang, Y.; Zhou, Y. G. J. Am. Chem. Soc. 2011, 133, 16432.

14. 14 Background: HEH as an Organic Catalyst Chen, Q. A.; Chen, M. W.; Yu, C. B.; Shi, L.; Wang, D. S.; Yang, Y.; Zhou, Y. G. J. Am. Chem. Soc. 2011, 133, 16432.

15. 15 Background: HEH as an Organic Catalyst Chen, Q. A.; Chen, M. W.; Yu, C. B.; Shi, L.; Wang, D. S.; Yang, Y.; Zhou, Y. G. J. Am. Chem. Soc. 2011, 133, 16432.

16. 16 Background: HEH as an Organic Catalyst Harsh conditions for the regeneration of HEH limit the substrate scope: limited to benzoxazinones Search for New NAD(P)H Analogs

17. 17 Their Inspiration Chen, Q. A.; Wang, D. S.; Zhou, Y. G.; Duan, Y.; Fan, H. J.; Yang, Y.; Zhang, Z. J. Am. Chem. Soc. 2011, 133, 6126.

18. 18 Background: New NAD(P)H Analog

19. 19 Development of New NAD(P)H Mimics: Ease of Phenanthridine Reduction

20. 20 Development of New Regenerable NAD(P)H Mimics

21. 21 Reaction Scope

22. 22 Reaction Scope

23. 23 Reaction Scope

24. 24 Reaction Scope

25. 25 Postulated Mechanism