title: The Organocatalytic Approach to Enantiopure 2H- and 3H-Pyrroles: Inhibitors of the Hedgehog Signaling Pathway.
abstract: A divergent approach to enantioenriched 2H- and 3H-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 2H-pyrroles to be a potent but nontoxic inhibitor of the Hedgehog signaling pathway by binding to the Smoothened protein.
authors.affiliation: Max-Planck-Institut für Kohlenforschung, Kaiser Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kötzner
authors.affiliation: Max-Planck-Institut für Kohlenforschung, Kaiser Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Leutzsch
authors.affiliation: Max-Planck-Institut für Molekulare Physiologie, Compound Management and Screening Center (COMAS), Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Sievers
authors.affiliation: Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
authors.forename: Sumersing
authors.initials: S
authors.lastname: Patil
authors.affiliation: Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227, Dortmund, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.affiliation: Max-Planck-Institut für Kohlenforschung, Kaiser Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Max-Planck-Institut für Kohlenforschung, Kaiser Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Thiel
authors.affiliation: Max-Planck-Institut für Kohlenforschung, Kaiser Wilhelm-Platz 1, 45470, Mülheim an der Ruhr, Germany. list@mpi-muelheim.mpg.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: List
mesh_terms: D001896:Boron Compounds / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D008968:Molecular Conformation; D010756:Phosphoric Acids / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D053823:Hedgehog Proteins; D010756:Phosphoric Acids; D011758:Pyrroles; C030242:phosphoric acid
keywords: 2H-pyrroles; 3H-pyrroles; Brønsted acid catalysis; Hedgehog signaling inhibitors; [1,5]-alkyl shifts