Synthesis and cytotoxic activity of some novel polycyclic γ-butyrolactones

Induction of apoptosis by cyclobutanones and derived polycyclic γ-lactones: a preliminary analysis of antiproliferative activity

“…23, 24 The obtained cyclobutanones (7a-f) were oxidized with H 2 O 2 -formic acid (BV oxidation) in methanol at room temperature to obtain carbocyclic fused γ-lactones; these were purified by column chromatography over silica gel (60-120 mesh, eluted with 5% ethyl acetate in hexane). 23, 24 The obtained cyclobutanones (7a-f) were oxidized with H 2 O 2 -formic acid (BV oxidation) in methanol at room temperature to obtain carbocyclic fused γ-lactones; these were purified by column chromatography over silica gel (60-120 mesh, eluted with 5% ethyl acetate in hexane).…”

“…Chemistry β-Ionone-derived chalcones (4a-f) were irradiated in aqueous methanol (1% v/v) leading to the formation of C11 exo compounds (6a-f), which rearrange on silica to furnish 5-aryl-7,11,11-trimethyltricycloij5.4.0.0 3,6 ]undec-1-en-4-ones (7a-f) in high yield. 23,24 The obtained cyclobutanones (7a-f) were oxidized with H 2 O 2 -formic acid (BV oxidation) in methanol at room temperature to obtain carbocyclic fused γ-lactones; these were purified by column chromatography over silica gel (60-120 mesh, eluted with 5% ethyl acetate in hexane). Purified major products (7a-f and 8a-f) were isolated in high yields (Scheme 1 and Table 1).…”

“…Earlier, we have reported the cytotoxic activity of para-substituted carbocyclic γ-lactones, and almost all compounds showed insignificant cytotoxicity, 24 which prompted us to synthesize some novel compounds (7a-f and 8a-f) with varied substitutions. Against the colon cancer cell line (HCT-116), compounds 7d and 8d showed promising inhibitory activity with IC 50 = 12 and 15, respectively, whereas compounds 7b, 7c and 8d exert moderate inhibitory potential.…”

“…21a In contrast, etoposide (2) and teniposide (3), which are two semisynthetic glycosidic 4′demethylepipodophyllotoxin derivatives, do not affect tubulin, but instead act by inhibiting DNA topoisomerase II (topo II). 23, 24 Therefore, we decided to synthesize some novel cyclobutanones and polycyclic γ-lactones by using the above method and evaluate them against human cancer cell lines, and also investigate the mechanism of induced cell death in cancer cells. 21c Various methods have been employed by chemists for the synthesis of fourand five-membered ketones.…”

“…22 Recently, we have reported a route to synthesize cyclobutanones through direct irradiation of IJE,E)-arylidene-β-ionones in aqueous solvents and then conversion to polycyclic γ-lactones through Baeyer-Villiger oxidation by using hydrogen peroxide as an oxidant. 23,24 Therefore, we decided to synthesize some novel cyclobutanones and polycyclic γ-lactones by using the above method and evaluate them against human cancer cell lines, and also investigate the mechanism of induced cell death in cancer cells.…”