韓国海綿から抗がん性化合物を合成(Soaking up the anti-cancer properties of a South Korean sea sponge)

2025-11-13 イェール大学

This illustration depicts the synthetic chemistry solution (left) for recreating a cancer-fighting molecule found in the marine sponge Phorbas gukhulensis.

<関連情報>

• https://news.yale.edu/2025/11/13/soaking-anti-cancer-properties-south-korean-sea-sponge
• https://www.science.org/doi/10.1126/science.aea9310

(–)-グクレニンAの3成分集合体と構造機能関係 Three-component assembly and structure–function relationships of (–)-gukulenin A

Vaani Gupta, Zechun Wang, Joshua B. Combs, Timothy Wright, […] , and Seth B. Herzon
Science  Published:13 Nov 2025
DOI:https://doi.org/10.1126/science.aea9310

Abstract

α-Tropolones comprise an unsaturated seven-membered ring bearing a hydroxyl substituent adjacent to a polarized carbon–oxygen π-bond. This polarization imparts a permanent molecular dipole and aromatic stabilization to the ring, resulting in unique physical properties, including affinity for divalent metals and ambiphilic reactivity. Among secondary metabolites that contain α-tropolones, the pseudodimeric isolate (–)-gukulenin A (7) stands out for its complexity and has shown promise in treating murine models of ovarian cancer. Here we describe an enantioselective synthesis of (–)-gukulenin A (7). Key steps include a directed C–H arylation, a tandem Grob fragmentation–alkylation, an innovative synthesis of methyl tropolone ethers, a multicomponent cross-coupling, and a thermal carbonyl–ene reaction. Structure–function studies establish the dimeric tropolone and aldehyde substructures as drivers of cytotoxicity.