Synthesis and antitumor activity of NO-donating CDDO analogues

The target compounds( 4a-4k ) were synthesized by building an α,β-unsaturated ketone moiety on C-ring of oleanolic acid (OA) via a five-step reaction sequence,yielding a CDDO analogue( 1 ),followed by coupling of C3-OH in Compound 1 with substituted furoxans using butanedioic acid as a linker.The structures of the target compounds were identified by IR,MS and ¹H NMR.The most active compound 4i displayed significant inhibitory effects(IC₅₀=0.8-1.4 μmol/L) against the proliferation of four human tumor cell lines(HepG2,BEL-7402,MCF-7 and Caco-2),and was as potent as the positive control 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester(CDDO-Me).Compound 4i is thus worthy of further studies.