Liquid-Phase Peptide Synthesis of Tropolone–Peptide Hybrid Antimalarials
Open Access
- 26 March 2026
- journal article
- Published by American Chemical Society (ACS) in Organic Letters
- Vol. 28 (14) , 4462-4467
Abstract
Tropolones are non-benzenoid aromatics with broad bioactivity, yet their inherent planarity and metal-chelating properties pose challenges to a medicinal chemistry campaign. We developed a liquid-phase peptide synthesis strategy that leveraged a hydrophobic TAG carrier to streamline condensation, deprotection, and purification steps, overcoming challenges that hinder traditional solution-phase derivatization of tropolones. Among the synthesized tropolone-peptide hybrid derivatives, the lead analogue exceeded antimalarial potency of puberulic acid and artemisinin, highlighting the advantage of three-dimensional peptide hybridization.Keywords
Funding Information
- Japan Agency for Medical Research and Development (JP25ama121035)
- Japan Society for the Promotion of Science (23K06197)
- Japan Society for the Promotion of Science (24K18256)
- Japan Society for the Promotion of Science (25K09877)
- Japan Society for the Promotion of Science (JP23H04884)
- Japan Society for the Promotion of Science (JP24H01789)
- Pharmaceutical Society of Japan
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