A scaleable process for the synthesis of two naturally occurringprocyanidins, namely (-)-epicatechin-(4
![](/images/gifchars/beta2.gif)
,8)-(+)-catechin (
1)and (-)-epicatechin-3-
O-galloyl-(4
![](/images/gifchars/beta2.gif)
,8)-(-)-epicatechin-3-
O-gallate (
2), is described. The key steps were highlighted byimprovements for the benzylation of (+)-catechin (
3), stereoselective reduction of the C-3 keto group of (2
R)-5,7,3',4'-tetrakis(benzyloxy)flavan-3-one (
10), and coupling between4-hydroxyethoxy-5,7,3',4'-tetra-
O-benzyl-(-)-epicatechin (
11)and 5,7,3',4'-tetra-
O-benzyl-(+)-catechin (
4) or 5,7,3',4'-tetra-
O-benzyl-(-)-epicatechin (
6), respectively. The debenzylationperformed in a biphasic system resulted in an improved yieldand purity of the target compounds. The chemistry was scaled-up to produce multigram quantities of the title compounds (
1and
2) for various
in vitro,
ex vivo, and
in vivo studies.Moreover, the scale-up process provided a detailed descriptionfor the preparation of multihundred to kilogram scale quantitiesof intermediates used in the synthesis of these two titledprocyanidins.