2. Academic Validation
  3. Total synthesis of bicyclic depsipeptides spiruchostatins C and D and investigation of their histone deacetylase inhibitory and antiproliferative activities

Total synthesis of bicyclic depsipeptides spiruchostatins C and D and investigation of their histone deacetylase inhibitory and antiproliferative activities

  • Eur J Med Chem. 2013 Feb:60:295-304. doi: 10.1016/j.ejmech.2012.12.023.
Koichi Narita 1,  Yurie Fukui,  Yui Sano,  Takao Yamori,  Akihiro Ito,  Minoru Yoshida,  Tadashi Katoh
Affiliations

Affiliation

  • 1 Laboratory of Synthetic and Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
PMID: 23313638 DOI: 10.1016/j.ejmech.2012.12.023
Abstract

The bicyclic depsipeptide histone deacetylase (HDAC) inhibitors spiruchostatins C and D were synthesized for the first time in a highly convergent and unified manner. The method features the amide coupling of a D-leucine-D-cysteine- or D-valine-D-cysteine-containing segment with a D-alanine- or D-valine-containing segment to directly assemble the corresponding seco-acids, key precursors of macrolactonization. The HDAC inhibitory assay and cell-growth inhibition analysis of the synthesized depsipeptides determined the order of potency of spiruchostatins A-D in comparison with the clinically approved depsipeptide FK228 (romidepsin). Novel aspects of structure-activity relationships (SAR) were revealed.

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