Abstract
A solid-phase synthesis protocol was developed, that enabled phenol-protected (-)-epicatechin, and (-)-epigallocatechin to be selectively linked to functionalised resins, as a method to investigate the mechanism of catechin oxidation, which during black tea manufacturing, leads to the ubiquitous and partially characterised thearubigins. Solid-phase synthesis was chosen because model oxidation of catechins can be undertaken, without the solution-phase disadvantage of producing undefined intermediates, and products, which are difficult to isolate. Although (-)-epigallocatechin has a lower redox potential than (-)-epicatechin, and is therefore required to be linked to the resin during oxidation to prevent uncontrolled oxidation-reduction dismutation, or oligomerisation, (-)-epicatechin was used as the model catechin to develop aspects of the synthetic protocol. The four phenol groups in (-)-epicatechin were selectively protected with the allyl protecting group. Phenol-protected (-)-epicatechin was then selectively linked, via the secondary, aliphatic 3-OH position, via a symmetrical diisopropylsilyl linker, to hydroxytentagel resin. The selective linkage was relatively high yielding (84.6%); however, solid-phase synthesis requires yields greater than 97%, rendering the protocol uneconomical. The five phenol groups in (-)-epigallocatechin were selectively protected with the allyl protecting group. Phenol-protected (-)-epigallocatechin was selectively linked, via the aliphatic, secondary 3-OH position, via a symmetrical diisopropylsilyl linker, a 1,4-disubstituted 1,2,3-triazole, and an amide bond, to aminotentagel resin in high yield (> 97%). The five allyl protecting groups were selectively removed with a palladium(0) catalyst. Subsequent chemical oxidation, with potassium hexacyanoferrate(III) and co-substrate (-)-epicatechin, led to one major, resin-linked product. The product was selectively cleaved from the resin by fluoride, and preliminary FT-IR, NMR and MS data were acquired. By substituting aminotentagel resin with PEGA resin, the synthetic protocol developed (linkage of (-)-epigallocatechin to a resin), can be used for the biomimetical oxidation of resin-linked catechins, using polyphenol oxidase and/or peroxidase.