Epicatechin reaction rates

Table 3.2 Relative Reaction Rates for the Reactions between Oxygen Free Radicals and Selected Antioxidant Compounds and (—)-Epicatechin... 

As expected, k2 for catechin and epicatechin are the same, since the reaction rate would be expected to be independent of C-ring stereochemistry. The comparatively smaller rate constants observed for the two procyanidins could be explained by the fact that they possess fewer reaction sites per monomer unit than catechin or epicatechin and also by steric effects. 

In addition to the effect pH has on the overall reaction rate, it is also important to note the effect of pH on rearrangement reactions of (+)-catechin. At alkaline pH, these secondary rearrangement reactions dominate. Epimerization of (+)-catechin to (-b)-epicatechin is a prominent reaction at pH 9.0. This is not serious in terms of adhesive formulation because it does not alter the reactivity of the aromatic nucleus toward condensation with benzyl alcohols. However, in reactions at pH 10.0 or 11.0, the intramolecular rearrangement to catechinic acid dominates and results in loss of the phloroglucinol functionality. 

PEDRIELLI p, PEDULLi G F and SKIBSTED L H (2001a) Antioxidant mechanism of flavonoids. Solvent effect on rate constant for chain-braining reaction of quercetin and epicatechin in autoxidation of methyl linoleate, JAgric Food Chem, 49, 3034-40. 

The last decade has seen quite remarkable advances in our knowledge of the structure and properties of the proanthocyanidins. Viscosity measurements were made of solutions of procyanidins isolated from Theobroma cacao and Chaenomeles speciosa with number-average degrees of polymerization of 6.1 and 11.8, respectively, in water and 1% sodium hydroxide at 25 °C. Procyanidins are apparently completely crosslinked by formaldehyde up to a chain length of 6 units, but few units are crosslinked in polymeric procyanidins. The second order rate constants observed for the formaldehyde reaction with catechin or epicatechin are approximately six times higher than that observed for the C. speciosa polymer. 

If the supply of NADPH is rate limiting, intermediate C-4 carbocations with either (2S) or (2/ )-stereochemistry could react with either (+ )-catechin (3) or (- )-epicatechin (30) (Fig. 12.1) to produce dimers or oligomers of procyanid-ins. The nucleophilic character at C-6 or C-8 can be used with either cation. The reactions would be regulated by the stability of the cations arising from flavan-3,4-diols. Furthermore, substitution occurs more readily at C-8 than at C-6. Substitution at nucleophilic centers is highly sensitive to ste-ric factors and reactions occur preferenially at the least hindered sites (Hillis, 1985). 

The situation is more complex in defining the regioselectivity of procyanidin synthesis. Here differences between kinetic control and thermodynamic equilibrium ratios become particularly important because of the lability of the in-terflavanoid bond in these compounds and because of differences in both the relative rate of acid-catalyzed cleavage and rate of condensation for the C-6 and C-8 substituted isomers (148). Work of Haslam s group indicated that the C-8 substituted procyanidins predominated over their C-6 linked pairs by a factor of 8 to 9 to 1 (177, 352). However, Botha et al. (28) obtained catechin-(4a- 8)-catechin and catechin-(4a- 6)-catechin in relative yields of 3.2 to 1 from a 2-hour bio-mimetic synthesis with 0.1 M HCl at ambient temperature. Similarly, Hemingway et al. (143) obtained epicatechin-(4)ff- 8)-catechin and epicatechin-(4)ff- 6)-cate-chin in relative yields of about 2.5 to 1 through synthesis by reaction of Pinus taeda proanthocyanidins with excess catechin for 48 hours at 25 °C using HCl as a catalyst. This ratio was similar to the yield of the two isomers isolated from the phloem of Pinus taeda. The extreme lability of the interflavanoid bond in the procyanidins causes one to wonder if true kinetic control ratios can be obtained from acid-catalyzed reactions of the procyanidins. 

Two other approaches to determination of a kinetic control ratio for substitution at the C-6 and C-8 positions of procyanidins have been attempted (139,148). Determination of the relative rate of cleavage of C-8 and C-6 regio-isomers (2.6-1) and a determination of their relative yields at the thermodynamic equilibrium (1.3-1) permitted an estimation of a kinetic control ratio of 3.3 1 for the C-8 and C-6 linked isomers (148). The other approach was to determine the ratio of the C-8 and C-6 linked dimers after synthesis by reaction of epicatechin-(4)ff)-phenylsulfide and catechin at pH 9.0 and ambient temperature through quinone methide intermediates (139). Here the C-8 and C-6 linked isomers were obtained in an approximate ratio of 3.5-4 1. These later results, together with evidence for interflavanoid linkage isomerism in trimeric and polymeric procyanidins (141,143) (Sect. 7.6.3.3), show that substitution is not as heavily favored at the C-8 position in procyanidins as had been thought. 

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