An enantiomerically pure bilirubin. Absolute configuration of (αR,α′R)-dimethylmesobilirubin-XIIIα

摘要: Abstract Enantiomerically pure (+)-(α R ,α′ )-dimethylmesobilirubin-XIIIα 1 and its (α S ) enantiomer ent - were synthesized in ten steps from simple precursors. Resolution was achieved at an early stage the synthesis, with a racemic monopyrrole precursor rac 6 being converted to amides 8 (1 )-camphor-2,10-sultam. of 99% d.e. accomplished three crystallizations, absolute configuration acid deduced by X-ray crystallography more crystalline, diastereomerically amide 7 . Circular dichroism spectroscopy showed intense bisignate Cotton effects: Δ e max 435 =+344, 391 =−193 (CHCl 3 ), as expected for molecular exciton, consistent P -helical intramolecularly hydrogen-bonded ridge-tile conformation. The effect magnitudes match almost exactly those found (−)-(β ,β′ 11 )-dimethylmesobilirubin-XIIIα. However, pseudo- meso diastereomer 12 is not zero. Its large positive exciton couplet H NMR NOE analysis confirm that α-CH exerts greater steric demand than β-CH —by factor ∼3.