Synthesis of heterocyclic triads by Pd-catalyzed cross-couplings and evaluation of their cell-specific toxicity profile.

Two complementary approaches for the preparation of linked 5-membered heterocycles were developed. The Pd-catalyzed Suzuki-Miyaura cross-coupling with halogenated furan, thiophene, and selenophene led to higher overall yields, but C,H-bond activation was a more efficient strategy for the coupling at C(2) of oxazoles. Potency and selectivity of the final hydroxymethyl products in renal (A498), lung (NCI-H226), kidney (CAKI-1), and breast (MDA-MB-468, MCF7) carcinoma cell lines were determined.