Abstract
Natural sesterterpenolides, luffarin I and luffarin A, from Luffariella geometrica have been synthesized, and this is the first reported synthesis of luffarin A. The Yamaguchi esterification of the nor-diterpenic fragment, obtained from 2.8–15 \(\upmu \)M, with the appropriate furane alcohols yielded the necessary diene intermediates for the synthesis of the target molecules. The key strategic step in this synthesis was the ring-closing metathesis (RCM) reaction of the diene intermediates. This strategy allowed for the synthesis of 16-epi-luffarin I and analogues for structure–activity relationship (SAR) studies. The most active compound exhibited antiproliferative activity against a panel of six human solid tumour cell lines with \(\hbox {GI}_{50}\) values in the range 2.8–15 M.
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Acknowledgments
The authors gratefully acknowledge the help extended by C. Raposo (MS) of the Universidad de Salamanca; and FSE, Junta de Castilla and León, BIO/SA74/13 for financial support. A.U. is grateful to the JCyL and FSE for his fellowship. J.M.P. thanks the EU Research Potential (FP7-REGPOT-2012-CT2012-31637-IMBRAIN), the European Regional Development Fund (FEDER), and the Spanish Instituto de Salud Carlos III (PI11/00840) for financial support. G.B.P. thanks Fundación CajaCanarias for a postgraduate grant.
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Urosa, A., Marcos, I.S., Díez, D. et al. Ring-closing metathesis as key step in the synthesis of Luffarin I, 16-epi-Luffarin I and Luffarin A. Mol Divers 20, 369–377 (2016). https://doi.org/10.1007/s11030-015-9638-7
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DOI: https://doi.org/10.1007/s11030-015-9638-7