Bischoff, Matthias ; Mayer, Peter ; Meyners, Christian ; Hausch, Felix (2024)
Enantioselective Synthesis of a Tricyclic, sp³‐Rich Diazatetradecanedione: an Amino Acid‐Based Natural Product‐Like Scaffold.
In: Chemistry – A European Journal, 2020, 26 (21)
doi: 10.26083/tuprints-00015975
Artikel, Zweitveröffentlichung, Verlagsversion
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: |
2024 |
| Autor(en): |
Bischoff, Matthias ; Mayer, Peter ; Meyners, Christian ; Hausch, Felix |
| Art des Eintrags: |
Zweitveröffentlichung |
| Titel: |
Enantioselective Synthesis of a Tricyclic, sp³‐Rich Diazatetradecanedione: an Amino Acid‐Based Natural Product‐Like Scaffold |
| Sprache: |
Englisch |
| Publikationsjahr: |
23 Januar 2024 |
| Ort: |
Darmstadt |
| Publikationsdatum der Erstveröffentlichung: |
2020 |
| Ort der Erstveröffentlichung: |
Weinheim |
| Verlag: |
Wiley-VCH |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: |
Chemistry – A European Journal |
| Jahrgang/Volume einer Zeitschrift: |
26 |
| (Heft-)Nummer: |
21 |
| DOI: |
10.26083/tuprints-00015975 |
| URL / URN: |
https://tuprints.ulb.tu-darmstadt.de/15975 |
| Zugehörige Links: |
|
| Herkunft: |
Zweitveröffentlichung DeepGreen |
| 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. |
|
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 |
| Status: |
Verlagsversion |
| URN: |
urn:nbn:de:tuda-tuprints-159754 |
| 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: |
23 Jan 2024 13:55 |
| Letzte Änderung: |
24 Jan 2024 07:25 |
| PPN: |
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| Zugehörige Links: |
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| Export: |
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| Suche nach Titel in: |
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Enantioselective Synthesis of a Tricyclic, sp³‐Rich Diazatetradecanedione: an Amino Acid‐Based Natural Product‐Like Scaffold. (deposited 23 Jan 2024 13:55)
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