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 (IC ₅₀ =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.