Highly Oxidized Ellagitannins of Carpinus japonica and Their Oxidation–Reduction Disproportionation

Abstract

In the research on ellagitannin metabolism, two unique dehydroellagitannins, carpinins E (1) and F (2), bearing dehydrohexa­hydroxy­diphenoyl (DHHDP) and hydrated biscyclo­hexenetrione dicarboxyl ester (HBCHT) groups, were isolated from young leaves of Carpinus japonica. Upon heating in H2O or treatment with pH 6 buffer at room temperature, 1 and 2 afforded the reduction product 3, isocarpinin A, with an (R)-hexahydroxy­diphenoyl (HHDP) group, suggesting the occurrence of redox disproportionation of the (S)-DHHDP group. This was supported by the increase in production of 3 in the pH 6 buffer solution by coexistence of epigallocatechin-3-O-gallate (15), accompanied by oxidation of 15. In contrast, treatment of 1 and 2 with ascorbic acid yielded 4, carpinin A, with an (S)-HHDP group. Upon heating with ascorbic acid, the HBCHT group was also reduced to an (S)-HHDP group, and 2 was converted to 2,3;4,6-bis­(S)-HHDP glucose. In leaves of C. japonica, the tannins 1 and 2 are dominant in young spring leaves, but compounds 3 and 4 become the major components of tannins in mature leaves. These results suggest that, in ellagitannin biosynthesis, oxidative coupling of the two galloyl groups first generates a DHHDP group, and subsequent reduction of DHHDP esters produces HHDP esters.

Ferroptosis-Inhibitory Difference between Chebulagic Acid and Chebulinic Acid Indicates Beneficial Role of HHDP

“…The chiral axis in HHDP may show different absolute configurations, ( R )- or ( S )-. Correspondingly, HHDP-containing tannins exist as two atropisomers [ 31 ]. From the perspective of organic stereochemistry, these two atropisomers are actually two diastereomers, some of which can be individually isolated from plants [ 32 ].…”

Formation of Dehydrohexahydroxydiphenoyl Esters by Oxidative Coupling of Galloyl Esters in an Aqueous Medium Involved in Ellagitannin Biosynthesis

“…Furthermore, we recently reported that some ellagitannin HHDP groups were reductively metabolized from DHHDP groups in the leaves of Castanopsis sieboldii , Triadica sebifera , Carpinus laxiflora , and Carpinus japonica [15] . Moreover, amariin and isoamariin having 3,6‐DHHDP esters and carpinins E and F with 2,3‐DHHDP esters were spontaneously degraded to 3,6‐HHDP and 2,3‐HHDP groups, respectively, in aqueous solutions at pH 6 and room temperature, and the reactions of the DHHDP groups were suggested to be a reduction‐oxidation disproportionation [15b,c] …”

“…CH 3 CN was stable at room temperature, heating of the solution at 85 °C converted 8 into 6 without a reducing agent (Figure S3), which supports the metabolic conversion of the DHHDP group into the HHDP group. This reaction can be considered to occur via a reduction‐oxidation disproportionation caused by an intermolecular electron transfer [15c] …”