Synthesis and Base-Catalyzed Transformations of Proanthocyanidins

Studies in Polyphenol Chemistry and Bioactivity. 1. Preparation of Building Blocks from (+)-Catechin. Procyanidin Formation. Synthesis of the Cancer Cell Growth Inhibitor, 3-O-Galloyl-(2R,3R)-epicatechin-4β,8-[3-O-galloyl-(2R,3R)-epicatechin]

“…The decaacetate 22 derived from our material exhibits 1 H and 13 C NMR spectra which are in good agreement with those reported by these authors for the decaacetate of the natural product. Selected 1 H NMR signals published for 22 derived from natural material 85a, agree also with ours, and appropriate 13 C NMR signals of our product agree with selected data published earlier for the decaacetate of natural and synthetic material 38a…”

“…Catechin is known to undergo quite readily a base-catalyzed epimerization at C-2 to form ent -epicatechin through reversible opening of ring C via a B-ring quinone methide intermediate 38a…”

“…The free epicatechin 4β,8-dimer ( 21 , procyanidin B 2 ) 31a,38a,, was uneventfully prepared from its benzylated precursor by hydrogenolysis. Only one set each of 1 H and 13 C NMR signals is observed, but the 1 H signals are close to the coalescence point at room temperature, and part of the 13 C signals are strongly broadened as well.…”

“…The synthetic challenge posed by proanthocyanidins is related to the difficulty in controlling the interflavan regio- and stereochemistry, as well as the sensitivity of the nonprotected compounds to acids, , bases, 1v,, and oxidizing agents . The condensation between flavan-3-ols and 4-substituted, electrophilic flavans has traditionally been performed without the use of phenol protecting groups in a mildly acidic medium 1v,31b,, or recently with AgBF 4 for SBn as the 4-substituent . The products are mixtures of regio- and sometimes stereoisomers, as well as higher oligomers despite the application of an excess of the nucleophilic building block.…”

Scale-Up Syntheses of Two Naturally Occurring Procyanidins: (−)-Epicatechin-(4β,8)-(+)-catechin and (−)-Epicatechin-3-O-galloyl-(4β,8)-(−)-epicatechin-3-O-gallate

“…Our interest is focused mainly at the cancer and vascular biology areas, where initial observations have shown different procyanidins to evoke different activities. − To unequivocally determine the natural oligomeric procyanidins associated with these activities and to confirm the structures assigned to these compounds, a synthesis program was initiated. − A series of oligomers of defined regio- and stereochemistry were synthesized for comparison to oligomers purified from cocoa extracts for structure−activity relationships in various in vitro , ex vivo , and in vivo models of assessment. The results from these initial studies has addressed some of the complex, synthetic challenges posed by the proanthocyanidins (condensed or nonhydrolyzable tannins) related to the difficulty in controlling the interflavan regio- and stereochemistry, as well as the sensitivity of the unprotected compounds to acid, alkali, and oxidizing environments. Through these efforts, 10−100 milligram quantities of some of these compounds have been made to confirm much of the in vitro results elaborated by the natural products. , However, in order to fully develop the potential clinical applications for this class of compounds and address pharmacological and toxicological requirements, 100 g to 1000 g levels of material are essential for full investigations.…”