A-Type Proanthocyanidins

The double interflavanyl linkage in A-type proanthocyanidins introduces a high degree of conformational stability which culminates in high-quality and unequivocal NMR spectra conspicuously free of the effects of dynamic rotational isomerism at the dimeric level. Compounds of this class are readily recognizable from the characteristic AB-doublet ( J3 4 = 3-4 Hz) of the C-ring protons in the heterocyclic region of their 

Both carbon-oxygen bonds of the acetal functionality in the procyanidin A-1 (91) and A-2 (92) derivatives are thus susceptible to reductive cleavage under acidic conditions. This process is presumably triggered by random protonation of the acetal oxygens and concomitant 

The protocol described here should thus contribute substantially towards a straightforward chemically orientated structural definition of the A-class proanthocyanidins. 

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On the other hand, the flavan-3-ol units can also be doubly linked by an additional ether bond between C2 07 (A-type). Structural variations occurring in proanthocyanidin oligomers may also occur with the formation of a second interflavanoid bond by C-0 oxidative coupling to form A-type oligomers (Fig. 3) [17,20]. Due to the complexity of this conversion, A-type proanthocyanidins are not as frequently encountered in nature compared to the B-type oligomers. 

The A-type proanthocyanidins are characterized by a second ether linkage between an A-ring hydroxyl group of the lower unit and C-2 of the upper unit. Since they are less frequently isolated from plants than the B-types, they have been considered unusual structures [18,19]. The first identified A-type proanthocyanidin was procyanidin A2 isolated from the shells of fruit of Aes-culus hippocastanum. Since then, many more A-type proanthocyanidins have been found in plants, including dimers, trimers, tetramers, pentamers and ethers [18,21]. 

Only a few studies have reported the antiprotozoal activity of proantho-cyanidins. Bioassay-guided fractioning of the extract of Geranium niveum led to the isolation of two new A-type proanthocyanidins epf-afzelechin-(4j6 8,2j6 0 7)-afzelechin and EC-(4/l 8,2/1 0 7)-afzelechin... 

Bilia, A.R. et al., Flavans and A-type proanthocyanidins from Prunus prostrata, Phytochemistry, 43, 887, 1996. 

Drewes, S.E. and Taylor, C.W., Methylated A-type proanthocyanidins and related metabolites from Cassipourea gwnmiflua. Phytochemistry, 31, 551, 1994. 

Prasad, D., Two A-type proanthocyanidins from Prunus armeniaca roots, Fitoterapia, 71, 245, 2000. 

A-type proanthocyanidins are often incorrectly named due to the fact that the DEF moiety in, e.g., trimeric analogs, is rotated through 180°. The proposed system cognizant of this aspect will thus be used. Proanthocyanidin A-2 (8) is thus named epicatechin-(2(3 7, 4(3 8)-epicatechin. The proper name for the trimeric analog 9 is epicatechin-(2(3 7, 4(3 8)-epicatechin-(4(3 8)-epicatechin. 

In addition to identification of flavan-3-ols and derivatives from natural sources (Table 11.3, Figure 11.3-Figure 11.5, Figure 11.7, and Figure 11.8), several synthetic studies and efforts at establishing absolute configuration have been reported. The modified Mosher method has been successfully applied to configurational definition of the flavan-3-ols and 4-arylflavan-3-ols, and the A-type proanthocyanidins. " The first stereoselective synthesis of a series of flavan-3-ol... 

The report on aesculitannins A-G from the seed shells of Aesculus hippocastanum demonstrates three important chemical methods to facilitate the unequivocal structural elucidation of the A-type proanthocyanidins. These protocols include thiolytic degradation using phenylmethanethiol in acidic medium, oxidative formation of the ether linkage when... 

Despite the apparent clarity of the nomenclature rules, several papers in the area of the A-type proanthocyanidins still lack proper implementation of these rules. The reader must therefore ascertain the correctness of published names. In addition, the reader is also referred to the growing body of evidence of the physiological importance of these compounds, data of which can be found in several of the papers listed in the references. 

FIGURE 11.17 Scheme 11.6 Proposed route to the reductive cleavage of both interflavanyl bonds in A-type proanthocyanidins including the structures of compounds 167-173. 

Cronje, A. et al.. Oligomeric flavanoids. Part 16. Novel prorobinetinidins and the first A-type proanthocyanidin with a 5-deoxy A- and a 3,4-cw-C-ring from the maiden investigation of commercial wattle bark extract, J. Chem. Soc., Perkin Trans. 1, 2467, 1993. 

Steynberg, P.J. et al., Oligomeric flavanoids. Part 25. Cleavage of the acetal functionality in A-type proanthocyanidins, Tetrahedron, 53, 2591, 1997. 

Foo, L.Y. et al., A-type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli, J. Nat. Prod, 63, 1225, 2000. 

Lou, H. et al., A-type proanthocyanidins from peanut skins. Phytochemistry, 51, 297, 1999. 

Calzada, F. et al., Geranins C and D, additional new antiprotozoal A-type proanthocyanidins from Geranium niveum, Planta Med., 67, 677, 2001. 

The flavan-3-ols (catechins), flavan-4-ols/flavan-3,4-diols (leucoanthocyani-dins), A-type proanthocyanidins, B-type proanthocyanidins including the... 

Maldonado, P.D. Rivero-Cruz, L Mata, R. Pedraza-Chaverri, J. 2005. Antioxidant activity of A-type proanthocyanidins from Geranium niveum (Geraniaceae). J. Agric. Food Chem. 53 1996-2001. 

Indirect evidence for the intermediacy of a /)-quinone methide of type (213) in the oxidative conversion of B- into A-type proanthocyanidins came from the oxidation of epigallocatechin (216) with the homogenate of banana fruit flesh polyphenol oxidase. " Besides racemization at C-2, the oxidative conversion also gave retro-ct-hydroxydihydrochalcone (219) (Scheme 24), presumably via initial oxidation of (216) to the B-ring quinone methide (217). Hydration gave the unstable hemiacetal (218) that would equilibrate with the 1,3-diarylketone (219). It was also shown that laccase (EC 1.10.3.2) catalyzed the conversion of procyanidin B-2 (5) into procyanidin A-2 (215). 

Balde, A.M. Pieters, L.A. Wray, V Kolodziej, H. Vanden Berghe, D.A. Claeys, M. Vlietinck, A.J. A-Type Proanthocyanidins from Stem Bark of Pavetta owariensis. Phytochemistry, 1991, 30, 337-342. 

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