Enantioselective Synthesis of Antiinfluenza Compound A-315675

Citations Over TimeTop 10% of 2002 papers

Abstract

Drug discovery efforts at Abbott Laboratories have led to the identification of influenza neuraminidase inhibitor A-315675 (1) as a candidate for development as an antiinfluenza drug. A convergent, stereoselective synthesis of this highly functionalized pyrrolidine is reported that utilizes pyrrolinone 2 as the key intermediate. The C5, C6 stereochemistry was established through a diastereoselective condensation of chiral imine compound 3 with silyloxypyrrole 4 to give pyrrolinone 2. The stereochemical outcome of this reaction depended critically on the choice of the imine functional group (FG), with tritylsulfenyl and (R)-toluenesulfinyl providing the desired products in good yields as crystalline intermediates. Conversion of pyrrolinone 2 into 1 was accomplished in seven subsequent steps, including Michael addition of cis-1-propenylcuprate at C4 and introduction of a cyano group as a carboxylic acid equivalent at C2.

Related Papers

• → Recent developments in enantioselective iron-catalyzed transformations(2019)58 cited
• → Optical Activation of 2-Phenylpropionaldehyde via Some 2-Substituted Pyrrolidine Enamines(1978)12 cited
• → Synthesis of pyrrolidine analogues of solamin(2005)10 cited
• → New Phosphorylated Derivatives of Piperidine and Pyrrolidine(1997)7 cited
• → Chiral B(III) Lewis Acids(2000)19 cited