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Bilirubin, the yellow pigment of jaundice, is a bichromophoric tetrapyrrole formed in mammals by heme catabolism. It readily adopts either of two enantiomeric folded conformations which are shaped like ridge tiles and are stabilized by a network of intramolecular hydrogen bonds. Interconversion of the conformational enantiomers is rapid at room temperature and may bc displaced toward either enantiomer by complexation with chiralagents. Intramolecular steric effects may also affect enantioselection

Bilirubin, the yellow pigment of jaundice, is a bichromophoric tetrapyrrole formed in mammals by heme catabolism. It readily adopts either of two enantiomeric folded conformations which are shaped like ridge tiles and are stabilized by a network of intramolecular hydrogen bonds. Interconversion of the conformational enantiomers is rapid at room temperature and may bc displaced toward either enantiomer by complexation with chiralagents. Intramolecular steric effects may also affect enantioselection

An inexpensive gram-scale, three-step procedure is described to convert methyl xanthobilirubinate and it alkanoic acid ester analogs (methyl 5-[(3-ethyl-1,5-dihydro-4-methyl-5-oxo-2H-pyrrol-2-ylidene)methyl]-1,4-dimethylpyrrol-3-ethanoate, -propanoate, -butanoate, -pentanoate, -hexanoate) into mesobilirubin-XIIIα and analogs in >90% yield at each step

(4Z,15Z)-Bilirubin IXα, the cytotoxic yellow tetrapyrrole pigment of jaundice, readily adopts either of two interconverting, enantiomeric conformations, which are stabilized through complementary intramolecular hydrogen bonding between the pyrrole and lactam N-H and C=O residues of one dipyrrinone moiety and the CO 2 H group of propionic acid side chains on the second dipyrrinone. One conformational enantiomer can be destabilized relative to the other through allosteric action by judicious placement of methyl groups in the propionic acid side chains. Thus, insertion of a methyl group at the pro-R site on the α-carbon of the propionic acid destabilizes the M-chirality intramolecularly hydrogen-bonded conformational enantiomer by introducing a severe nonbonded CH 3 |CH 3 steric interaction with a pyrrole methyl substituent

Dipyrrinone analogs of xanthobilirubic acid, 5-[1,5-didehydro-3-ethyl-4-methyl-5-oxo-2H-pyrrol-2-ylidene)-methyl]-2,4-dimethyl-1H-pyrrol-3-propanic acid, with alkanoic acid chain lengths varying from formic to caproic have been synthesized as their methyl esters and characterized spectroscopically. All of the dipyrrinones studied exhibit intermolecular hydrogen bonding in chloroform, as detected by 1 H-nmr, and the influence of the carboxyl group on the uv-visible spectrum decreases with increasing chain length

Chiroptical properties of the title compounds have been studied. The influence of the substitution pattern of the aromatic ring and the configuration of the centre of chirality on the Cotton effects appearing in various wavelengths ranges are discussed.

Conformational analysis of (4Z, 15Z)-bilirubin-IX(alpha) by molecular mechanics computations reveals a global energy minimum folded conformation. Powerful added stabilization is achieved through intramolecular hydrogen bonding. Theoretical treatment of bilirubin as a molecular exciton predicts an intense bisignate circular dichroism spectrum for the folded conformation: (Delta) (epsilon) is congruent to 270 L (DOT) mole-1 (DOT) cm-1 for the $OM450 nm electronic transition(s). Synthesis of bilirubin analogs with propionic acid groups methylated at the (alpha) or (beta) position introduces an allosteric effect that allows for an optical resolution of the pigments, with enantiomers exhibiting the theoretically predicted circular dichroism.© (1991) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

2,3-Dihydro-2-aryl-1,5-benzothiazepin-4(5)-ones and 2,3-disubstituted 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones have hitherto been synthesized by heating the mixture of 2-aminothiophenol and appropriately sub-stituted acrylic acids without solvent.2–7 This is a very simple and convenient method, but because of the accompanying decompositions, the yield of the reaction is generally quite poor (20 − 40%). For this reason, it seemed expedient to work out new procedures for the synthesis of these biologically important benzothiaze-pines. Preparation of 2,3-dihydro-2-phenyl-1,5-benzothia-zepin-4(5H)-one (20) was achieved by the ring enlargement of 1-thioflavanone8 but, because of the difficulties in the synthesis of the 1-thiochromanone deriva-tives in some cases, this procedure could hardly be generalized.

Optically active 2,3-dihydro-1,5-benzothiazepin-4(5H)-ones (14–17) have been synthesizedvia resolution and chemical transformation of nitrocarboxylic acids6–9. Starting from the latter various optically active substances have been synthesized as well. Optical purity was checked by NMR spectroscopy.

The absolute configuration of (−)-(1′R,3S)-4 has been determined by X-ray diffraction. The UV- and CD-spectra of the title compound8 and the intermediates for its synthesis are discussed. The stronger Cotton effects can be explained by application of the exciton theory to the observed CD-couplets. The CD of the lower homologue9 of known absolute configuration is in full agreement with that of homochirally analogue8.