Synthesis and applications of epicatechin and epiafzelechin derivatives from proanthocyanidins

Abstract

Proanthocyanidins (PAs), one of the most ubiquitous groups of plant polyphenols, are the natural polymer widespread throughout the plant kingdom but their application as raw materials for fine chemicals are largely unexplored. This thesis documented the results on the effort towards chemical conversion of PAs into epicatechin and epiafzelechin derivatives with potential application such as multidentate chiral ligands.

Mangosteen pericarps proanthocyanidins (MPPs) were extracted with 0.66% yield (dry matter) from mangosteen peels, agricultural waste in South East Asian countries. 13C{1H} and 1H NMR signals showed the presence of predominantly procyanidins together with a few prodelphinidin units along with small amounts of stereoisomers of afzelechin/epiafzelechin and gallocatechin/ epigallocatechin. Depolymerization of MPPs with benzylmercaptan indicated that the mean degree of polymerization (mDP) is 6.6. The electrospray ionization¿mass spectrometry (ESI-MS) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectra revealed the dominant B type oligomers with mainly epicatechin units and with a small amount of A-type oligomers.

MPPs and CPs extracted in our lab were compared with commercial pine bark proanthocyanidins (PBPs) and grape seed proanthocyanidins (GSPs) via MALDI-TOF-MS and thiolysis analysis. Both thiolysis and MALDI-TOF-MS results indicated that MPPs were ideal for synthesis of the new chiral ligands due to the higher mDP and ratio of epicatechin units.

MPPs were depolymerized with selective carbon and sulfur nucleophiles. The products were purified by column chromatography and characterized with ESI-MS/MS and NMR spectrometry. After screening the selective protecting reagents of the B-ring ortho-dihydroxyl groups, the depolymerized products were applied for one or two step reaction and finally sixteen chiral epicatechin derivatives were synthesized.

Dethiolation was observed in two sulfur-containing epicatechin derivatives. In order to synthesize stable sulfur-containing ligands, proanthocyanidins from the rhizomes Selliguea feei (FSPs), were extracted and characterized. FSPs are mainly A-type propelargonidin dimer and trimers. Then, three sulfur-containing epiafzelechin derivatives were synthesized together with a rare alkaloidal A-type propelargonidin.

Kinetics of the dethiolation of three sulfur-containing epicatechin derivatives under weakly basic conditions were investigated and the mechanism of the base-catalyzed condensation was proposed. The results indicated that epicatechin derivative 8 is an ideal intermediate for synthesis of bioactive natural products such as procyanidin B2 and some rare alkaloidal flavonoid under very mild conditions.