Synthesis of cytochalasan analogues with aryl substituents at position 10.

Autor:	Javorská Ž; Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague, Czech Republic. perlikop@vscht.cz., Rimpelová S; Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic., Labíková M; Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague, Czech Republic. perlikop@vscht.cz., Perlíková P; Department of Organic Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Technická 5, 166 28 Prague, Czech Republic. perlikop@vscht.cz.; Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, 160 00 Prague, Czech Republic.
Jazyk:	angličtina
Zdroj:	Organic & biomolecular chemistry [Org Biomol Chem] 2024 Jun 05; Vol. 22 (22), pp. 4536-4549. Date of Electronic Publication: 2024 Jun 05.
DOI:	10.1039/d4ob00634h
Abstrakt:	Cytochalasans are fungal metabolites that are known to inhibit actin polymerization. Despite their remarkable bioactivity, there are few studies on the structure-activity relationship (SAR) of the cytochalasan scaffold. The full potential of structural modifications remains largely unexplored. The substituent at position 10 of the cytochalasan scaffold is derived from an amino acid incorporated into the cytochalasan core, thus limiting the structural variability at this position in natural products. Additionally, modifications at this position have only been achieved through semisynthetic or mutasynthetic approaches using modified amino acids. This paper introduces a modular approach for late-stage modifications at position 10 of the cytochalasan scaffold. Iron-mediated cross-coupling reactions with corresponding Grignard reagents were used to introduce aryl or benzyl groups in position 10, resulting in the synthesis of six new cytochalasan analogues bearing non-natural aromatic residues. This methodology enables further exploration of modifications at this position and SAR studies among cytochalasan analogues.
Databáze:	MEDLINE
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