Ring-closing metathesis as key step in the synthesis of Luffarin I, 16-epi-Luffarin I and Luffarin A.

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 2.8-15μM, 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 [Formula: see text] values in the range 2.8-15 M.