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Updated: Jul 2, 2026

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis and activity of largazole analogues with linker and macrocycle modification
Yongcheng Ying1, Yanxia Liu, Seong Rim Byeon
1Department of Chemistry, Duke University, Durham, North Carolina 27708, USA.
Abstract:
To characterize largazole's structural requirements for histone deacetylase (HDAC) inhibitory and antiproliferative activities, a series of analogues with modifications to the side chain or 16-membered macrocycle were prepared and biologically evaluated. Structure-activity relationships suggested that the four-atom linker between the macrocycle and octanoyl group in the side chain and the (S)-configuration at the C17 position are critical to repression of HDAC activity. However, the valine residue in the macrocycle can be replaced with alanine without significant loss of activity.
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