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, October 16, 2012

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, October 16, 2012

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 Background: NADH and NADPH in Living Cells Anaerobic Conditions

5 Glyceraldehyde-3-phosphate Dehydrogenase

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

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

9 Relative Hydride Donor Ability of HEH

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

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

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

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,

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,

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,

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 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 Background: New NAD(P)H Analog

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

20 Development of New Regenerable NAD(P)H Mimics

21 Reaction Scope

22 Reaction Scope

23 Reaction Scope

24 Reaction Scope

25 Postulated Mechanism