Resolution of chiral interconvertible diastereoisomers of a 2,18-bridged biliverdin mediated by first-order asymmetric transformation

Abstract

Chiral diastereoisomers of the bridged biliverdin 2,18-(1′,4′-dimethoxybutane-1′,4′-diyl)-8,12-bis(2″-methoxycarbonylethyl)-3,7,13,17-tetramethylbilin-1,19-(21H,24H)-dionerac-(1a) and rac-(1b) have been resolved and isolated from the four-component mixture. Repetitive enrichment of M-helical isomers with (R)-(–)-mandelic acid followed by chromatographic separation afforded one enantiomer of each diastereoisomeric pair, viz. (M-SS)-(1a) and (M-RR)-(1b). The corresponding enantiomorphic species (P-RR)-(1a) and (P-SS)-(1b) were each obtained from their respective diastereoisomeric counterpart by thermal conversion. The enantiomeric purities achieved (>95%) were checked by n.m.r. techniques. The rotational strengths R(absolute values) of the visible c.d. bands exhibited by the diastereoisomers of (1) are close to one another and similar to those reported for open-chain bilatrienes. The influence of chirality centres on helical excess (h.e.) and helicity of the bridged bilatriene moiety and its pronounced solvent dependence is discussed.