Xanthobilirubic acid and its amides. Synthesis, spectroscopy, and solution structures

Abstract

Xanthobilirubic acid, 5‐[1,5‐didehydro‐3‐ethyl‐4‐methyl‐5‐oxo‐2H‐pyrrol‐2‐ylidene)methyl]‐2,4‐dimethyl‐1H‐pyrrol‐3‐propanoic acid, its methyl ester, amide, N‐methylamide and dimethylamide, and kryptopyrromethenone have been synthesized and characterized spectroscopically. In d6‐DMSO solution all pyrromethenones were monomeric, with lactam and pyrrole N‐Hs H‐bonded to solvent. In deuteriochloroform, the pyrromethenones preferred a dimeric form, with intramolecular H‐bonding between the lactam C = 0 of one unit and the lactam and pyrrole N‐Hs of the second.

Initial Photochemistry of Bilirubin Probed by Femtosecond Spectroscopy

“…In order to elucidate bilirubin's chemistry, complicated by exciton coupling and hydrogen bonding, model compounds as xanthobilirub(in)ic acid, XBR, and its methyl ester, MeXBR, have been synthesized and used in several studies. − Due to the structural similarities with BR, even these dipyrrinone compounds tend to form hydrogen bonds by dimerization in nonpolar solvents. − To mimic BR's intramolecular hydrogen bonding in single dipyrrinone units, on the other hand, compounds with flexible alkane chains have been synthesized and proven to engage in internal hydrogen bonding. − …”

Synthesis of water-soluble bile pigments bound to amine-ended monomethoxypolyethyleneglycol: thiol addition and attempted enzymatic reduction of a bilindione derivative

“…Small deviations from this behaviour have not been considered significant and a planar dimeric form has been proposed for them as well. This is the case for the model XBR methyl amide where the lactam and pyrrole NHs (obtained by extrapolation from the spectra in CDCl 3 -DMSO-d 6 mixtures) have been reported to appear at 10.9 and 10.1 ppm respectively [14]. It is also the case for XBR MPEG ester, in which the NHs appear at 10.8 and 10.2 ppm [5].…”

“…All other solvents were rendered oxygen-free, argon saturated by several cycles of degassing under vacuum at room temperature under magnetic stirring followed by argon saturation. The synthesis of the following compounds is described in the literature: xanthobilirubic acid, 1 [14], biliverdin-IXh, 4 [8,15], polyethylene glycol mono-methyl ether amino derivative (MPEG-NH 2 ) [16]. The cytosolic fraction from rat liver was obtained according to the following procedure: immediately after the sacrifice of the rats, the liver was extracted and homogenized in 3 vol (w/v) of 0.25 mol dm −3 sucrose in a Potter-Elvejhem apparatus.…”

“…Xanthobilirubic acid, 1, was obtained by total synthesis as previously reported [14]. The monomethoxypolyethyleneglycol amide of xanthobilirubic acid, 1-MPEGA, was prepared by reaction of the free acid, 1, with monomethoxypolyethyleneglycol amine, MPEG-NH 2 , [16] using dicyclohexylcarbodiimide/dimethylaminopyridine (DCC/DMAP) as the coupling reagent in dry dichloromethane [5].…”

“…Due to the difficulty in separating 1-MPEGA from unreacted MPEG-NH 2 , and in order to favour the conversion of all MPEG-NH 2 , an approximate 10% molar excess of 1 was used. In spite of this precaution, the isolated amide, 1-MPEGA, contained approximately 30% MPEG-NH 2 , as deduced from the m value in the UV-VIS spectrum of the reaction product in CH 2 Cl 2 , and assuming for the pure amide the literature value [14] for xanthobilirubic acid methyl amide. The amide 1-MPEGA was identified spectroscopically: in the IR, the amide C O band near 1670 cm −1 overlaps the chromophore lactam C O band; in the UV-VIS, the spectrum in water (u max = 412 nm) is similar to that in CH 2 Cl 2 (u max = 407 nm) with a slight broadening of the absorption band in water, perhaps due to some aggregation.…”