Preparation of Pyrrolidine-Based PDE4 Inhibitors via Enantioselective Conjugate Addition of α-Substituted Malonates to Aromatic Nitroalkenes
| Autor: | Nicole A. LeFur, Kevin Koch, Anthony D. Piscopio, Paul J. Nichols, Tsung-Hsun Chuang, John Demattei, Bradley R. Barnett |
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| Rok vydání: | 2006 |
| Předmět: |
Addition reaction
Pyrrolidines Molecular Structure Stereochemistry Chemistry Organic Chemistry Enantioselective synthesis Stereoisomerism General Medicine Alkenes Nitro Compounds Combinatorial chemistry Biochemistry Malonates Pyrrolidine Cyclic Nucleotide Phosphodiesterases Type 4 Stereocenter chemistry.chemical_compound Malonate 3' 5'-Cyclic-AMP Phosphodiesterases Michael reaction Pyrrolidinones Physical and Theoretical Chemistry PDE4 Inhibitors Conjugate |
| Zdroj: | Organic Letters. 8:1495-1498 |
| ISSN: | 1523-7052 1523-7060 |
| DOI: | 10.1021/ol060398p |
| Popis: | [reaction: see text] The enantioselective conjugate addition of alpha-substituted malonates to aromatic nitroalkenes generates a stereocenter at the carbon bearing the aromatic group and an adjacent prochiral center from the alpha-substituted malonate. Nitro reduction followed by diastereoselective cyclization provides pyrrolidinones with two contiguous stereocenters, one of which is quaternary. This sequence was used for the preparation of the PDE4 inhibitor IC86518. Additional examples of the enantioselective Michael addition illustrate the scope of the reaction. |
| Databáze: | OpenAIRE |
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