Highly Enantioselective Catalytic Vinylogous Propargylation of Coumarins Yields a Class of Autophagy Inhibitors. Issue 37 (28th July 2017)

• Record Type: Journal Article
• Authors: Xu, Hao; Laraia, Luca; Schneider, Laura; Louven, Kathrin; Strohmann, Carsten; Antonchick, Andrey P.; Waldmann, Herbert
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 37(2017)
• Page Start: 11232
• Page End: 11236
• Publication Date: 2017-07-28
• Subjects: asymmetric catalysis -- copper -- drug discovery -- heterocycles -- propargylic compounds; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201706005
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: A highly enantioselective copper‐catalyzed vinylogous propargylic substitution has been developed. Aromatic and aliphatic propargylic esters react smoothly with substituted coumarins under mild reaction conditions to give the desired products with excellent yields and enantioselectivities. Subsequent single‐step transformations enable the synthesis of a wide range of multifunctional and diverse compounds, and allow the efficient combination of different natural product fragments. Investigation of the obtained compound collection in cell‐based assays monitoring changes in phenotype led to the discovery of a novel class of autophagy inhibitors. Abstract : Class act : In the copper‐catalyzed title reaction, aromatic and aliphatic propargylic esters react with substituted coumarins to give the desired products in excellent yields and enantioselectivities. Single‐step transformations enabled the synthesis of several compounds. Biological investigation of the compound collection led to the discovery of a novel class of autophagy inhibitors.