Total synthesis and biological evaluation of histone deacetylase inhibitor WF-3161

Michael Kohr; Niklas Papenkordt; Manfred Jung; Uli Kazmaier

doi:10.1039/d3ob00641g

Total synthesis and biological evaluation of histone deacetylase inhibitor WF-3161

Org Biomol Chem. 2023 May 31;21(21):4382-4387. doi: 10.1039/d3ob00641g.

Authors

Michael Kohr¹, Niklas Papenkordt², Manfred Jung², Uli Kazmaier¹

Affiliations

¹ Organic Chemistry, Saarland University, D-66123 Saarbrücken, Germany. u.kazmaier@mx.uni-saarland.de.
² Institute of Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104 Freiburg, Germany.

PMID: 37194325
DOI: 10.1039/d3ob00641g

Abstract

A novel synthesis of the naturally occurring HDAC inhibitor WF-3161 is described. Key steps include the Matteson homologation to generate the stereogenic centres in the side chain, and Pd-catalysed C-H functionalisation to connect the side chain to the peptide backbone. WF-3161 was found to be highly selective for HDAC1, whereas no activity was observed towards HDAC6. High activity was also found against the cancer cell line HL-60.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Histone Deacetylase 6
Histone Deacetylase Inhibitors* / chemistry
Histone Deacetylases* / metabolism
Peptides

Substances

Histone Deacetylase Inhibitors
WF 3161
Histone Deacetylases
Histone Deacetylase 6
Peptides