Design and synthesis of 4-arylidenetetrahydrocurcumins

A novel series of 4-arylidene tetrahydrocurcumins was synthesized from tetrahydrocurcumin and various aldehydes via Knoevenagel condensation in 81–90% yield. Aliphatic and aromatic aldehydes substituted with electron-donating and withdrawing groups were found to be effective substrates. The synthesized compounds were characterized using various spectroscopic techniques, and the structure of one of the derivatives was unambiguously established by single-crystal X-ray diffraction. These compounds were designed as a resemblance of combretastatin A4 scaffold integrated with curcumin. Our design and synthesis offer 4-arylidene tetrahydrocurcumin derivatives as a new class of compounds for evaluating bioactivity, with improved bioavailability, stability, and therapeutic efficacy.