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1 1In previous work we have used the term mono ionized, in the sense of formation of ions. This was the term used for ions resulting from the acid‐base reactions and the respective constants were defined as ionization constants.

2 2In any case, both processes are well separated in time and the respective amplitude can be obtained.

3 3In the case of 4’‐hydroxyflavylium the trans‐chalcones are almost 100% of CB and thus equilibrium is achieved with AH+ and the trans‐chalcones.

4 4Flash photolysis is applied when there is excited state flavylium/quinoidal base proton transfer.

5 5In the case of two derivatives bearing one acylated unit, the compound with the three glucoside units has the highest effect.

6 6It is possible to observe the blue color at pseudo‐equilibrium in other systems. The peculiar behavior of HBA1 is that the purplish and blue colors are observed at equilibrium.

7 7In principle, other analytical techniques, such as nuclear magnetic resonance (NMR), can be used to access the ratio FLV/Ct. The timer can be used only for a certain time interval (a few hours), because the spectral variations at the end of the reaction become very small.

Ken Ohmori and Keisuke Suzuki

Department of Chemistry, Tokyo Institute of Technology, Japan

Keywords:A‐type, afzelechin; catechin; epiafzelechin; epicatechin; flavan; flavonoid; oligomer; proanthocyanidin; procyanidin;

The oligomeric proanthocyanidins (PAs), i.e. the condensed tannins, constitute a large class of natural polyphenols with an extreme structure diversity. Although some of these compounds proved to show significant biological activities, such as antiviral, antibacterial, and antitumor effects, detailed studies on their biological effects at the molecular level have remained premature due to the scarce availability of pure samples. The natural products are generally obtained as a complex mixture of closely related compounds, which are hardly separable even with the aid of modern separation methods. In view of the potentially interesting bioactivities in individual compounds, this is an unfortunate situation, but may be solved by organic synthesis if general, effective synthetic routes to these compounds were developed. Given a sufficient supply of homogeneous samples for the biological study, one may expect discovery of enhanced biological activities and have access to synthetic congeners and probes for further research on the mode of action.

The tremendous structural diversity of oligomeric PAs has its origin in the combination of several elements:

1 Difference in the constituting monomers: Figure 2.1shows the representative flavan‐3‐ols contained as the monomers in the naturally occurring oligomeric PAs; that is, afzelechin (AZ), epiafzelechin (EZ), catechin (CA), epicatechin (EC), gallocatechin (GC), epigallocatechin (EGC) and their C(5)‐deoxy congeners, guibourtinidol, fisetinidol, and robinetinidol. They differ in the hydroxylation level of the A‐ring (one or two hydroxy groups) and the B‐ring (one, two, or three hydroxy groups), and in the relationship of the C‐ring substituents, cis or trans.

2 Single connectivity (B‐type): Figure 2.2shows the linear oligomers characterized by a single C–C interflavan linkage at the C(4)–C(8) position. This connectivity is schematically represented in section I of the figure. By a historic convention from the early days of catechin research, these compounds with single connectivity are called the B‐type (vide infra). The linear oligomers formed by an array of the single (B‐type) interflavan linkages constitute a huge variety of molecular entities, differing in the degree of oligomerization and in the constituent monomers. A broad range of oligomers—small to large—is seen, ranging from dimers to higher oligomers, exceeding dodecamers. Various monomers, such as AZ, EZ, CA, EC, GC, EGC, are uniformly included to form homo‐oligomers or heterogeneously included to form hetero‐oligomers. In addition, as schematically expressed by section II of Figure 2.2, the oligomers with the C(4)–C(6) interflavan bonds are also found as the minor members with type‐B linkages. Figure 2.1 Origin of the structural diversity in oligomeric PAs: structural diversity of monomers.