Synthesis and Biological Evaluation of a Depsipeptidic Histone Deacetylase Inhibitor via a Generalizable Approach Using an Optimized Latent Thioester Solid-Phase Linker.
J Org Chem
; 85(12): 8253-8260, 2020 06 19.
Article
em En
| MEDLINE
| ID: mdl-32452203
ABSTRACT
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 IC50 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Depsipeptídeos
/
Inibidores de Histona Desacetilases
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article