Enantioselective synthesis of a tricyclic, sp³‐rich diazatetradecanedione: an amino acid‐based natural product‐like scaffold

Bischoff, Matthias ; Mayer, Peter ; Meyners, Christian ; Hausch, Felix (2020)
Enantioselective synthesis of a tricyclic, sp³‐rich diazatetradecanedione: an amino acid‐based natural product‐like scaffold.
In: Chemistry – A European Journal, 26 (21)
doi: 10.1002/chem.201905144
Artikel, Bibliographie

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Kurzbeschreibung (Abstract)

6‐, 7‐, and 8‐membered rings are assembled from a linear precursor by successive cyclisation reactions to construct a tricyclic diazatricyclo[6.5.1.0⁴,⁹]‐tetradecanedione scaffold. Advanced building blocks based on d‐aspartic acid and l‐pyroglutamic acid were combined by a sp³−sp² Negishi coupling. A carbamate‐guided syn‐diastereoselective epoxidation followed by an intramolecular epoxide opening allowed the construction of the piperidine ring. An efficient one‐pot hydroxyl‐group protection twofold deprotection reaction prepared the ground for the cyclisation to the bicycle. A final deprotection of the orthogonal protecting groups and lactamisation led to the novel, sp³‐rich tricycle. The final compound is a substrate mimic of peptidyl‐prolyl cis‐trans isomerases featuring a locked trans‐amide bond. Cheminformatic analysis of 179 virtual derivatives indicates favourable physicochemical properties and drug‐like characteristics. As proof of concept we, show a low micromolar activity in a fluorescence polarisation assay towards the FK506‐binding protein 12.

Typ des Eintrags:

Artikel

Erschienen:

2020

Autor(en):

Bischoff, Matthias ; Mayer, Peter ; Meyners, Christian ; Hausch, Felix

Art des Eintrags:

Bibliographie

Titel:

Enantioselective synthesis of a tricyclic, sp³‐rich diazatetradecanedione: an amino acid‐based natural product‐like scaffold

Sprache:

Englisch

Publikationsjahr:

2020

Ort:

Weinheim

Verlag:

Wiley-VCH

Titel der Zeitschrift, Zeitung oder Schriftenreihe:

Chemistry – A European Journal

Jahrgang/Volume einer Zeitschrift:

(Heft-)Nummer:

DOI:

10.1002/chem.201905144

Zugehörige Links:

TUprints Zweitveröffentlichung

Kurzbeschreibung (Abstract):

Alternatives oder übersetztes Abstract:

Alternatives Abstract	Sprache
sp³-Enriched scaffolds: Using simple amino acids, an elaborated synthesis was designed to construct a rigid tricyclic scaffold consisting of six-, seven- and eight-membered rings.	Englisch

Freie Schlagworte:

amino acids, diastereoselective epoxidation, FK506-binding protein, natural products, sp³−sp² Negishi coupling

Sachgruppe der Dewey Dezimalklassifikatin (DDC):

500 Naturwissenschaften und Mathematik > 540 Chemie

Fachbereich(e)/-gebiet(e):

07 Fachbereich Chemie
07 Fachbereich Chemie > Clemens-Schöpf-Institut > Fachgebiet Biochemie

Hinterlegungsdatum:

24 Jan 2024 07:26

Letzte Änderung:

24 Jan 2024 07:26

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