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

Isoplagiochin C 1 was prepared for the first time in 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 (PA,PB,P)-3 and (MA,PB,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.

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(P)-1,1′-Binaphthyl-2,2′-dicarboxylic-acid-1,1′-isoplagiochin-C-diesterC50H32O6CD (MeOH): λmax (Δε) [nm (M−1 cm−1)] = 212 (33.1), 213 (30.0), 215 (34.4), 220 (23.9), 233 (113), 258 (−15.7), 267 (0.581), 301 (−48.6)Source of chirality: isoplagiochin C and (P)-1,1′-binaphthyl-2,2′-dicarboxylic acidAbsolute configuration: (MA,PB,P)

(P)-1,1′-Binaphthyl-2,2′-dicarboxylic-acid-1,1′-isoplagiochin-C-diesterC50H32O6CD (MeOH): λmax (Δε) [nm (M−1 cm−1)] = 210 (148), 224 (46.3), 230 (64.3), 256 (−52.6), 274 (−8.57), 301 (−60.0)Source of chirality: isoplagiochin C and (P)-1,1′-binaphthyl-2,2′-dicarboxylic acidAbsolute configuration: (PA,PB,P)