Asymmetric Synthesis of Highly Functionalized Tetrahydropyran DPP-4 Inhibitor
| Autor: | Feng Xu, Yoshinori Kohmura, Michael J. Zacuto, Jon Rosen, Jeremy P. Scott, Andrew D. Gibb, Mahbub Alam, David M. Tschaen |
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| Rok vydání: | 2014 |
| Předmět: |
Dihydropyran
Stereochemistry Glycine Biochemistry Reductive amination Catalysis Ruthenium Stereocenter Kinetic resolution chemistry.chemical_compound Cycloisomerization Hypoglycemic Agents Enzyme Inhibitors Physical and Theoretical Chemistry Amination Dipeptidyl-Peptidase IV Inhibitors Molecular Structure Organic Chemistry Enantioselective synthesis Stereoisomerism Tetrahydropyran Kinetics Hydroboration chemistry Pyrones Oxidation-Reduction |
| Zdroj: | Organic Letters. 16:5422-5425 |
| ISSN: | 1523-7052 1523-7060 |
| Popis: | A practical synthesis of a highly functionalized tetrahydropyran DPP-4 inhibitor is described. The asymmetric synthesis relies on three back-to-back Ru-catalyzed reactions. A Ru-catalyzed dynamic kinetic resolution (DKR) reduction establishes two contiguous stereogenic centers in one operation. A unique dihydropyran ring is efficiently constructed through a preferred Ru-catalyzed cycloisomerization. Hydroboration followed by a Ru-catalyzed oxidation affords the desired functionalized pyranone core scaffold. Finally, stereoselective reductive amination and subsequent acidic deprotection afford the desired, potent DPP-4 inhibitor in 25% overall yield. |
| Databáze: | OpenAIRE |
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