Synthesis, spectroscopic and anti‐tumor studies of polyphenol‐linoleates derived from natural polyphenols

Abstract

An efficient first synthesis of di-, hexa-and octa-esters (octadeca-Z-9,12-dienoates, linoleates) from natural 1,5-bis-(4'-hydroxyphenyl)penta-Z-1,4-diene (Ginkgo biloba L.), (-)-epigallocatechin and (-)-epigallocatechin-3-O-gallate (jasmine tea/green tea), respectively, was developed. Using dicyclohexyl carbodiimide as an activating reagent in the presence of a catalytic amount of 4-dimethylaminopyridine in the polyesterification reactions gave di-, hexa-and octa-products (4), (7), and (8), respectively, in quantitative yields. A three-step efficient procedure for the synthesis of 1,5-bis-[4'-O-(octadec-Z-9",12"-dienoate)phenyl]penta-Z-1,4-diene (4) was also developed. The key step in the synthesis involved a stereoselective Wittig diolefination reaction that produced the penta-Z-1,4-diene system of (4). 1 H and 13 C NMR and MS techniques confirmed the structures of the esters. The esterified compounds were tested for in vitro anti-tumor activities against four and three human cancer cell lines at NCNPR and at NCI, respectively. They were found inactive as they failed to inhibit 50% growth of these cancer cells.