Premium
The Organocatalytic Approach to Enantiopure 2 H ‐ and 3 H ‐Pyrroles: Inhibitors of the Hedgehog Signaling Pathway
Author(s) -
Kötzner Lisa,
Leutzsch Markus,
Sievers Sonja,
Patil Sumersing,
Waldmann Herbert,
Zheng Yiying,
Thiel Walter,
List Benjamin
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201602932
Subject(s) - enantiopure drug , hedgehog signaling pathway , hedgehog , chemistry , stereochemistry , signal transduction , biochemistry , catalysis , enantioselective synthesis
Abstract A divergent approach to enantioenriched 2 H ‐ and 3 H ‐pyrroles catalyzed by a spirocyclic phosphoric acid is reported that makes use of a Fischer‐type indolization and a [1,5]‐alkyl shift. Catalyzed by the chiral phosphoric acid STRIP, good to excellent yields and enantioselectivities could be obtained. Remarkably, biological evaluation reveals one of these novel 2 H ‐pyrroles to be a potent but nontoxic inhibitor of the Hedgehog signaling pathway by binding to the Smoothened protein.