j. am. chem. soc. 2012 , 134 , 2442-2448 october 16, 2012
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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
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
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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)
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Background: NADH and NADPH in Living Cells
AnaerobicCondition
s
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Glyceraldehyde-3-phosphate Dehydrogenase
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Fatty Acid Biosynthesis
How good hydride donors are NADH and NADPH?
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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.
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Relative Hydride Donor Ability of HEH
Richter, D.; Mayr, H. Angew. Chem. Int. Ed. 2009, 48, 1958.
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Relative Hydride Donor Ability of HEH
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Background: HEH As an Organic Reagent
Mayer, S.; List, B. Angew. Chem. Int. Ed. 2006, 45, 4193.
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Background: HEH As an Organic Reagent
Rueping, M.; Antonchick, A. P.; Theissmann, T. Angew. Chem. Int. Ed. 2006, 45, 6751.
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Background: HEH as an Organic Catalyst
Will reduce pyridine without reducing the imineRegioselectivity of the reduction
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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.
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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.
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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.
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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
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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.
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Background: New NAD(P)H Analog
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Development of New NAD(P)H Mimics: Ease of Phenanthridine Reduction
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Development of New Regenerable NAD(P)H Mimics
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Reaction Scope
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Reaction Scope
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Reaction Scope
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Reaction Scope
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Postulated Mechanism
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