Procyanidin stereochemistry

Kozikowski, A.P., Tuckmantel, W., and George, C., Studies in polyphenol chemistry and bioactivity. 2. Establishment of interflavan linkage regio- and stereochemistry by oxidative degradation of an 0-alkylated derivative of procyanidins B2 to (R)-(—)-2,4-diphenylbutyric acid, J. Org. Chem., 65, 5371, 2000. 

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. 

The B-ring substitution pattern influences the absorbance. Pure prodelphinidin polymers show much lower specific absorption coefficients (El% = 62) than pure procyanidin polymers (E 0/o = 130) [141]. The molar absorption coefficients of dimeric and higher oligomeric procyanidins are similar (see Tab. (8)). The overall UV absorbance of an oligomer approximately amounts to the sum of the absorbances of the monomer units [226,254], However, UV detection of individual procyanidins after chromatographic separation implies that - in this case - molar absorbances depend on structure. In the series (+)-catechin, procyanidin B2, Cl and a tetramer molar absorbances decreased [262], Treutter et al. [154] found lower molar absorbances for dimers with a 2,3-cis stereochemistry (procyanidin B2 and B5) compared to (-)-epicatechin and (+)-catechin which nearly showed identical molar calibration plots. The molar absorbance of the doubly-linked procyanidin A2 was much higher than the ones of the monomers. 

Analysis of these molecules is particularly complex, due to the great structural diversity resulting from the number of hydroxyl groups, their position on the aromatic nuclei, the stereochemistry of the asymmetrical carbons in the pyran cycle, as well as the number and type of bonds between the basic units. In spite of the progress made in liquid chromatography, mass spectrometry and NMR, all of the structures have not been analyzed only the procyanidin dimers and some of the trimers have been completely identified. 

The prodelphinidins are less well characterized. Barley and beer contain a biflavan which gives catechin and delphinidin (58) on treatment with acid in agreement with structure (53) with either procyanidin B-1 or B-3 stereochemistry [51, 54]. Evidence for the occurrence of a [catechin-gallocatechin]... 

The structures of procyanidins 35-38 were assigned on a basis of H-NMR spectra of the decaacetates. The absolute stereochemistry has been determined as (45) for compounds (38) and (36) and (4/ ) for compounds (37) and (35). Mixtures of these particular dimers have not been found, but other dimers and trimers have been detected with them (Hillis, 1985 Porter, 1988). C-NMR spectra are especially useful for analyses of these compounds because a pronounced 7 effect (— 4.5 ppm) is observed and the chemical shift of C-2 is dependent on the orientation of the substituent at C-4 of the flavan system. All major natural procyanidin dimers possess a /ra/w-orientation of the hydroxyl group at... 

The most important members, however, are proanthocyanidin polymers, also called nonhydrolyzable or condensed tannins. Proanthocyanidin polymers exist as chains of C-4-C-8 (or C-6) linked flavan-3-ol units (Fig. 318). The monomer unit may be based on either of two stereochemistries designated as cis and trans and on either of two B-ring hydroxylation patterns, the procyanidin (PC) and the prodelphinidin (PD) units. Thus the polymer chains are characterized by the average stereochemistry and the PC PD ratios (Table 56). 

The procyanidins are broadly distributed in the leaves, fruit, bark, and less commonly the wood of a wide spectrum of plants (Sect. 7.7). About 50 procyanidins ranging from dimers to pentamers have now been isolated and their structures defined. The 2/ ,3/ -(2,3-c/5 )-procyanidins linked by (4)8- 8)- and/or (4)8- 6)-inter-flavanoid bonds occur most frequently. Many plants contain mixtures of 2R,3R-(2,3-cis) and 2R,3S-(2,3-trans) procyanidins but the compounds of the former stereochemistry normally predominate. The distribution of these compounds in commercially important woody plants has been extended continually from the early work of Porter (300) on Pinus radiata bark through the survey of Pinaceae by Samejima (329) to the recent isolation of dimers from the bark of Juniperus communis (94). The plants that contain predominantly 2R,3S- 2,3-trans) compounds are, so far, restricted to few plant genera, including fruits of Ribes species or the catechins of Salix species. All 2,3-cis procyanidins have [4-)8]-interflavanoid bonds (i.e., 3,4-/wa25 configuration). Most natural 2y3-trans procyanidins isolated to date have [4-a]-interflavanoid bonds (i.e. also 3 A-trans but opposite configuration). However, Delcour et al. (68) and Kolodziej (210, 211) have recently ob-... 

Nearly all of the procyanidins isolated to date have either catechin or epicate-chin as terminal units. It is common to find 2/ ,3i -(2,3-c/5 )-stereochemistry for the procyanidin extender units and a 2/ ,3S-(2,3-/AiflrA25 )-configuration for the terminal unit. The catechin-(4a- 8)-epiafzelchin dimer isolated from Wisteria sinensis by Weinges (380) and the catechin-(4a- 2)-phloroglucinol isolated from Nelia meyeri by Kolodzeij (208) are the only natural procyanidins reported to date that are not terminated with either catechin or epicatechin. Nelia meyeri also contains epicatechin-(4)ff- 8)-epicatechin and epicatechin-(4)ff- 6)-epicatechin (209). 

Delcour J A, Serneels E J, Ferreira D, Roux D G 1985 Synthesis of condensed tannins. Part 13. The first 2,3- ra/i5-3,4-c/5 procyanidins sequence of units in a trimer of mixed stereochemistry. J Chem Soc Perkins Trans I 669-676... 

Condensed tannins, when present in a woody plant, may not always exhibit a constant structure throughout the plant. There are a number of examples of this phenomenon known Acacia species commonly elaborate both 5-oxy and -deoxy-flavanoid tannins (for example, profisetinidins and procyanidins) in the wood (34) and bark (140), and exclusively 5-oxy-flavanoids and associated flavanoids (for example, quercetin glycosides) in the leaves (20, 138). Other examples include many Ribes species that commonly contain prodelphinidins. These are predominantly of the gallocatechin-4 (6) type in the leaves, but with the contrasting epigallocatechin-4 (3) stereochemistry in the fruits (37). Further, the tannins of Pinus radiata display contrasting structures between the bark in which 2,3-trans stereochemistry, catechin-4 (5), procyanidin polymers predominate, and tannins in the phloem, needles, male cones, and winter buds, in which a variety of mixed procyanidin and prodelphinidin polymers exist with predominantly 2,3-c/5 stereochemistry (Thble 7.7.5). 

Thus there are many examples of a contrasting B-ring oxidation pattern found between the proanthocyanidin units and the terminal flavan-3-ol units. Also, as pointed out by Haslam, there are many examples of contrasting stereochemistry between these units in procyanidins (57), and our work has shown that this is equally true of prodelphinidins (37). 

From this, and from the fact that feeding experiments by Haslam s and Stafford s groups have shown that the efficiency of labelling in procyanidin units is much higher than for the flavan-3-ol terminal units of dimers, it is tempting to speculate that the two types of unit may sometimes be derived from quite distinct biosynthetic pathways in the plant, so that these pathways are not always in direct sequence. The oxidation pattern and stereochemistry of the proanthocyanidin and chain-terminating groups will, therefore, not always be the same. 

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