Catechins, condensation synthesis

In a few cases, the synthesis was directed towards well-defined oligomers (dimers, trimers, etc.). The synthesis of bis(5,7,3, 4 -tetra-0-benzyl)-EC 4/1,8-dimer from 5,7,3, 4 -tetra-0-benzyl-EC and 5,7,3, 4 -tetra-0-benzyl-4-(2-hydroxyethoxy)-EC was described by Kozikowski et al. [41]. This compound exhibited the ability to inhibit the growth of several breast cancer cell fines through the induction of cell cycle arrest in the Gq/Gi phase. Analogously, procyanidin-B3, a condensed catechin dimer, has been obtained through condensation of benzylated catechin with various 4-0-alkylated flavan-3,4-diol derivatives in the presence of a Lewis acid. This reaction led to protected procyanidin-B3 and its diastereomer. In particular, octa-O-benzylated procyanidin-B3 has been produced with high levels of stereoselectivity and in excellent isolation yields [42]. 

Delcour, J.A., Ferreira, D., and Roux, D.G., Synthesis of condensed tannins part 9. The condensation sequence of leucocyanidin with (-l-)-catechin and with the resultant procyanidins. J. Chem. Soc. Perkin Trans. /1711, 1983. 

Delcour, J.A., D. Ferreira, and D.G. Roux Synthesis of Condensed Tannins. Part 9. The Condensation Sequence of Leucocyanidin with (-h)-Catechin and with the Resultant Procyanidins. J. Chem. Soc., Perkin Trans. 1, 1711 (1983). 

Young DA, Young E, Roux DG, Brandt EV, Ferreira D (1987) Synthesis of condensed tannins. 19. Phenol oxidative coupling of (-t)-catechin and (-t)-mesquitol - conformation of bis-(-l-)-catechins. J Chem Soc Perkin Trans 1 2345-2351... 

The situation is more complex in defining the regioselectivity of procyanidin synthesis. Here differences between kinetic control and thermodynamic equilibrium ratios become particularly important because of the lability of the in-terflavanoid bond in these compounds and because of differences in both the relative rate of acid-catalyzed cleavage and rate of condensation for the C-6 and C-8 substituted isomers (148). Work of Haslam s group indicated that the C-8 substituted procyanidins predominated over their C-6 linked pairs by a factor of 8 to 9 to 1 (177, 352). However, Botha et al. (28) obtained catechin-(4a- 8)-catechin and catechin-(4a- 6)-catechin in relative yields of 3.2 to 1 from a 2-hour bio-mimetic synthesis with 0.1 M HCl at ambient temperature. Similarly, Hemingway et al. (143) obtained epicatechin-(4)ff- 8)-catechin and epicatechin-(4)ff- 6)-cate-chin in relative yields of about 2.5 to 1 through synthesis by reaction of Pinus taeda proanthocyanidins with excess catechin for 48 hours at 25 °C using HCl as a catalyst. This ratio was similar to the yield of the two isomers isolated from the phloem of Pinus taeda. The extreme lability of the interflavanoid bond in the procyanidins causes one to wonder if true kinetic control ratios can be obtained from acid-catalyzed reactions of the procyanidins. 

Delcour J A, Ferreira D, Roux D G 1983 Synthesis of condensed tannins. Part 9. The condensation sequence of leucocyanidin with catechin and resultant procyanidins. J Chem Soc Perkin Trans I 1711-1717... 

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