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Total Synthesis of Gastrodinol via Photocatalytic 6π Electrocyclization
Yong-Feng Lv1,2, Fu-Cai Ren1,2, Meng-Ting Kuang1,2
1State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, P.R. China.
Abstract:
The first total synthesis of gastrodinol, an unprecedented poly-p-cresol-substituted natural product with a rearranged and reconstructed C ring moiety, is reported. Our synthesis features a convergent fragment approach. The Sonogashira coupling reaction forges the two segments together to furnish the conjugated ene-yne. Photocatalytic 6π electrocyclization followed by spontaneous aromatization is used to construct the tetrasubstituted B ring at the late stage. Further study shows that gastrodinol exhibits significant cytotoxic activity against five human cancer cell lines in vitro (IC50 2.5-3.8 μM).
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