title: Synthesis of a hexahydropyrrolo indole (HPI) compound library.
abstract: Scaffolds of natural products represent promising starting points for the development of focused compound libraries. Here, we describe the development of a synthetic route to a compound library based on the hexahydropyrrolo indole (HPI) scaffold, the denoting structural motif of the HPI natural product family. To this end, a two-step approach consisting of a batch synthesis of an advanced functionalizable HPI intermediate followed by the establishment of reaction conditions that allow derivatization of this scaffold at three different positions is described. Subsequently, the optimized methods were applied to the synthesis of a 276-member library.
authors.affiliation: Chemical Biology, Zentrum für Medizinische Biotechnologie (ZMB), Fakultät für Biologie, Universtität Duisburg-Essen, Universitätsstr. 2, 45117 Essen, Germany.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Nickel
authors.affiliation: Chemical Biology, Zentrum für Medizinische Biotechnologie (ZMB), Fakultät für Biologie, Universtität Duisburg-Essen, Universitätsstr. 2, 45117 Essen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Nickel
authors.affiliation: Chemical Biology, Zentrum für Medizinische Biotechnologie (ZMB), Fakultät für Biologie, Universtität Duisburg-Essen, Universitätsstr. 2, 45117 Essen, Germany.
authors.forename: Marco
authors.initials: M
authors.lastname: Hellmert
authors.affiliation: Chemical Biology, Zentrum für Medizinische Biotechnologie (ZMB), Fakultät für Biologie, Universtität Duisburg-Essen, Universitätsstr. 2, 45117 Essen, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ernst
authors.affiliation: Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GF, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Jewell
authors.affiliation: Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GF, United Kingdom.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Pearce
authors.affiliation: Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GF, United Kingdom.
authors.forename: Geraint
authors.initials: G
authors.lastname: Jones
authors.affiliation: Sygnature Discovery, BioCity, Pennyfoot Street, Nottingham NG1 1GF, United Kingdom.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hamza
authors.affiliation: Chemical Biology, Zentrum für Medizinische Biotechnologie (ZMB), Fakultät für Biologie, Universtität Duisburg-Essen, Universitätsstr. 2, 45117 Essen, Germany. Electronic address: markus.kaiser@uni-due.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Kaiser
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis*; D061565:Cycloaddition Reaction; D055808:Drug Discovery; D007211:Indoles / Q000138:chemical synthesis*; D015394:Molecular Structure; D054852:Small Molecule Libraries / Q000138:chemical synthesis*
chemical_list: D001688:Biological Products; D007211:Indoles; D054852:Small Molecule Libraries
keywords: Compound library; European Lead Factory; Hexahydropyrrolo indole (HPI); Natural product; Synthesis