Procyanidin oligomers. A new method for 4→8 interflavan bond formation using C8-boronic acids and iterative oligomer synthesis through a boron-protection strategy

Interest in the synthesis of procyanidin (catechin or epicatechin) oligomers that contain the 4 -> 8 interflavan linkage remains high, principally due to research into their health effects. A novel coupling utilising a C8-boronic acid as a directing group was developed in the synthesis of natural procyanidin 83 (i.e., 3,4-trans-(+)-catechin-4 alpha -> 8-(+)-catechin dimer). The key interflavan bond was forged using a novel Lewis acid-promoted coupling of C4-ether 6 with C8-boronic acid 16 to provide the a-linked dimer with high diastereoselectivity. Through the use of a boron protecting group, the new coupling procedure was extended to the synthesis of a protected procyanidin trimer analogous to natural procyanidin C2. (C) 2011 Elsevier Ltd. All rights reserved.