Reaction of flavanoids with mercaptoacetic acid

Abstract

Flavanoids are shown to react with mercaptoacetic acid at both benzylic positions, C-2 and C-4. Flavan-4-ols bearing no substituents in the B-ring undergo substitution (S_N1) to yield (flavan-4α-ylthio)acetic acids. 4′-Methoxyflavan on the other hand is attacked at the 2-position with cleavage of the heterocyclic ring. 4′-Methoxyflavan-4β-ol, which can be readily attacked at both positions, can be caused by an increase of the pH of the reaction mixture to react exclusively at the 4-position. Desulphurisation of the resulting substituted methyl mercapto-acetates occurs readily with Raney nickel and affords new routes for removal of a 4-hydroxy-group from a flavanoid or for reductive ring opening.

(+)-Methyl 2,3-cis-3,4-trans-(3-hydroxy-3′,4′,5,7-tetramethoxyflavan-4-ylthio)acetate, a degradation product from Calluna tannin, has been synthesised from (–)-epicatechin via(–)-2,3-cis-3,4-trans-3′,4′,5,7-tetramethoxy-flavan-3,4-diol.