Title
Total Synthesis of (15R)‐ and (15S)‐Prostaglandin A2
Author
Christoph Alberti
Fachbereich Chemie, Institut für Pharmazie, Universität Hamburg
Theresa Bock
Fachbereich Chemie, Institut für Pharmazie, Universität Hamburg
... show all
Abstract
From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ-aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5-dimethoxy-tetrahydrofuran employing an organocatalytic domino-aldol reaction, a Mizoroki-Heck reaction, a Wittig reaction as well as an oxidation-decarboxylation sequence. The (15R)-epimer significantly reduced GABA-induced currents through GABAA receptors while its (15S)-epimer did not show any significant effect. These data suggest that (15R)-PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators.
Keywords
Total synthesisProstaglandinsNatural productsGABAA receptorElectrophysiology
Object type
Language
English [eng]
Persistent identifier
phaidra.univie.ac.at/o:2112932
Appeared in
Title
Chemistry – A European Journal
Volume
30
Issue
50
ISSN
0947-6539
Issued
2024
Publication
Wiley
Version type
Date issued
2024
Access rights
Rights statement
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