Stereogenic competition in bilirubin conformational enantiomerism

Optically active bilirubin analogs (1 and 2) with a stereogenic center in each propionic acid side chain were synthesized and examined by CD and NMR spectroscopy. Introduction of an alpha-methyl and a beta-methyl forces the pigment to adopt either a left-handed (M) or right-handed (P) helicity with a folded, ridge-tile conformation. As evidenced by exciton-type circular dichroism spectra, the (alpha S, alpha'S-3), (beta S, beta'S-5), (alpha S, beta'S-1) stereoisomers strongly prefer the M-helicity ridge-tile conformation, but the (alpha R, beta'S) stereoisomer (2) prefers the P-helicity. (C) 1997 Elsevier Science Ltd.