Synthesis of Water-Soluble Curcumin Analogues
Authors:
Phillip Hernandez, Tracy TumbaleMentor:
Philip Hernandez, Professor of Chemistry, California State University Channel IslandsCurcumin, a yellow pigment that comes from the root of turmeric, has been observed to have beneficial health benefits including having activity toward several forms of cancer, drug resistant bacteria, and malaria, and inhibiting HIV Protease and β-Secretase. Unfortunately, these studies have been limited by the poor water-solubility of curcumin and it concomitant low bio-availability in the body. The concept behind this research is to synthesize a curcumin analogue that is soluble in the body at physiological pH. To accomplish, this we are preparing curcumin analogs which possess a water-solubilizing amine group that would impart a charge to the curcumin analog and, hence, water-solubility. To achieve this end, we have prepared aminoethyl-alkylated analogs of vanillin to be used as precursors to the water-soluble curcumin analogs. We report that the best approach to the synthesis of these molecules involves the alkylation of vanillin and other hydroxybenzaldehydes with 2-chloroethyl-substituted amines in acetonitrile. Yields are fair (approximately 60%) as a result of competing N-alkylation of the O-alkylated hydroxybenzaldehyde product. These amine-containing benzaldehydes will be converted into curcumin analogues by performing an Aldol condensation with a diketone under reduced pressure conditions.