Enantiopure isoplagiochin C by directed deracemization through axis-to-axis chirality transfer

Isoplagiochin C 1 was prepared for the first time in an enantiopure form from synthetic racemic material, using a novel stereochemical concept. This macrocyclic bisbibenzyl contains two biaryl axes. Of these, axis A is configurationally stable by its fixation within the macrocyclic framework, while axis B is stereochemically unstable. By diesterification of rac-1 with enantiopure (P)-1,1'-binaphthyl-2,2'-dicarboxylic acid, axis B is locked in its P-configuration, thus allowing the resolution and separate saponification of dilactones (P-A,P-B,P)-3 and (M-A,P-B,P)-3 to give the pure enantiomers of 1. This concept permits recycling of any undesired enantiomer of 1 by thermal equilibration of the respective diastereomer of 3. (C) 2013 Elsevier Ltd. All rights reserved.