A highly diastereoselective vinylogous Mannich condensation and 1,4-conjugate addition of (Z)-propenyl cuprate in the synthesis of an influenza neuraminidase inhibitor |
| |
| Affiliation: | 1. Department of Chemistry, Innovative Drug Research Center, Shanghai University, Shanghai 200444, PR China;2. Key Laboratory of Synthetic Organic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China;3. Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China;4. Laboratory for Microstructures, Instrumental Analysis and Research Center of Shanghai University, Shanghai 200444, PR China;1. Department of Chemistry and Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China;2. Shanghai Key Laboratory of Functional Materials Chemistry, East China University of Science and Technology, Shanghai 200237, China |
| |
| Abstract: | A practical synthesis of neuraminidase influenza inhibitor, A-322278, has been developed. Asymmetry is introduced into the synthesis by an enzyme mediated ester hydrolysis. A highly diastereoselective vinylogous Mannich condensation reaction of N-Boc-2-tert-butyldimethylsilyloxypyrrole (TBSOP) and an N-(triphenylmethylsulfenyl)imine proceeds under thermodynamic control to assemble the framework. A significant temperature dependent rate difference for the transfer of (Z)- and (E)-propenyl moieties from a cuprate reagent during a 1,4-conjugate addition was observed. A very selective addition of cyanide to an N-acyliminium intermediate was employed to control the final stereocenter. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
