Synthesis and cytotoxicity screening of substituted isobenzofuranones designed from anacardic acids.

This work is part of a large program, which seeks to discover new antitumor isobenfuranones designed from anacardic acids. The synthetic strategy for the construction of the title compounds takes into consideration the use of inexpensive anacardic acids (2), the major natural cashew (Anacardium occidentale) nut-shell phenolic lipid, and features one-pot construction of fused-ring aromatic gamma-lactones, phthalides. The cytotoxicity screening in different human cancer cell lines (HL-60 leukemia, SF295 glioblastoma and MDA-MB435 melanoma) by the MTT assay showed that acyclic precursor (6), and isobenfuranones (1a and 1b) are active compounds. Interestingly, 1a exhibits significant antiproliferative effect against HL-60 cells and moderate activity against SF295 and MDA-MB435 cell lines. Analysis of mechanisms involved in the cytotoxic activity showed that active compounds were leading to DNA damage, triggering apoptosis or necrosis induction.

(+)- and (-)-mutisianthol: first total synthesis, absolute configuration, and antitumor activity.

The first synthesis of the natural product (+)-mutisianthol was accomplished in 11 steps and in 21% overall yield from 2-methylanisole. The synthesis of its enantiomer was also performed in a similar overall yield. The absolute configuration of the sesquiterpene (+)-mutisianthol was assigned as (1S,3R). Key steps in the route are the asymmetric hydrogenation of a nonfunctionalized olefin using chiral iridium catalysts and the ring contraction of 1,2-dihydronaphthalenes using thallium(III) or iodine(III). The target molecules show moderate activity against the human tumor cell lines SF-295, HCT-8, and MDA-MB-435.