Synthesis and Biological Evaluation of a Depsipeptidic Histone Deacetylase Inhibitor via a Generalizable Approach Using an Optimized Latent Thioester Solid-Phase Linker.

Autor: Zang X; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Peraro L; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Davison RT; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Blum TR; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Vallabhaneni D; Department of Biology, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Fennell CE; Department of Biology, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Cramer SL; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Shah HK; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Wholly DM; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Fink EA; Department of Molecular Biology and Chemistry, Christopher Newport University, Newport News, Virginia 23606, United States., Sivak JT; Department of Molecular Biology and Chemistry, Christopher Newport University, Newport News, Virginia 23606, United States., Ingalls KM; Department of Molecular Biology and Chemistry, Christopher Newport University, Newport News, Virginia 23606, United States., Herr CT; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Lawson VE; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Burnett MR; Department of Biology, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Slade DJ; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Cole KE; Department of Molecular Biology and Chemistry, Christopher Newport University, Newport News, Virginia 23606, United States., Carle SA; Department of Biology, Hobart and William Smith Colleges, Geneva, New York 14456, United States., Miller JS; Department of Chemistry, Hobart and William Smith Colleges, Geneva, New York 14456, United States.
Jazyk: angličtina
Zdroj: The Journal of organic chemistry [J Org Chem] 2020 Jun 19; Vol. 85 (12), pp. 8253-8260. Date of Electronic Publication: 2020 Jun 09.
DOI: 10.1021/acs.joc.0c00854
Abstrakt: We describe the synthesis of Xyzidepsin, a depsipeptidic analogue of HDAC inhibitor Romidepsin (FK228), using a solid-phase strategy. Our latent thioester solid-phase linker was synthesized in 92% yield (three steps). Chemoselective conditions unmasked the thioester functionality and cyclized the depsipeptidic macrocycle. An IC 50 value of 0.50 μM ± 0.05 was obtained for U937 cells. This synthetic route, well-suited to SAR, represents a generalizable route toward all manner of analogues, including structures with acidic and basic amino acids.
Databáze: MEDLINE
Externí odkaz: