First chemical synthesis report of an anthocyanin metabolite with in vivo occurrence: cyanidin-4′-O-methyl-3-glucoside

Anthocyanins are natural polyphenolic compounds with important biological properties. In humans, these compounds are metabolized into different derivatives namely methyl, glucuronyl, and sulfate conjugates. Among these, cyanidin-4'-O-methyl-3-glucoside, already detected in vivo, seems to be an interesting metabolite to be used as standard for biological studies. The lack of suitable standards is a major drawback in biological studies. Bearing this in mind, this work describes a strategy for the chemical synthesis of cyanidin-4'-O-methyl-3-glucoside 9, which involved in the synthesis of the 'Western' and 'Eastern' molecules, namely 2,4-diacetoxy-6-hydroxybenzaldehyde 2 and 2-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-3'-benzyloxy-4'-methoxyacetophenone 8, respectively. The final step consisted in the Robinson's acidic aldol condensation between 2 and 8 molecules, which after the respective deprotections yield product 9. (C) 2013 Elsevier Ltd. All rights reserved.