An Intramolecularly Hydrogen Bonded Dihydrotripyrrinone

Abstract

A yellow tripyrrole analog (1) of bilirubin has been synthesized, and its lone propionic acid group is found to engage in conformation determining, intramolecular hydrogen bonding in solution and in the crystal. Molecular modelling and X-ray crystallography reveal an abbreviated ridge-tile or L-shape conformation in which an essentially planar dipyrrinone is hydrogen bonded to the single opposing propionic acid group. In the (arbitrary) (P)-helicity ridge-tile, the torsion angles about C(10) are computed to be 55 and 61 by molecular dynamics and found to be 66 and 53 in the crystal. Such torsion angles lead to an interplanar dihedral angle ($93 ) between the dipyrrinone and its adjoining pyrrole that is very close to the dihedral angle ($98 ) found in intramolecularly hydrogen bonded bilirubin.

An improved coupling procedure for the barton‐zard pyrrole synthesis

“…Pyrrole 1b was prepared in 78% yield using potassium carbonate in tetrahydrofuran-ethanol. In either 1a or 1b, the yields are higher than those reported previously using the BartonZard procedure with TMG or DBU as base [8,10,11], and they are much higher than those obtained by multistep conversion of 5.…”

“…α-Tosylpyrroles 2a and 2b have been shown to be very useful precursors to 3-methyl-4-ethyl-3-pyrrolin-2-one (4) [8][9][10] and 3-ethyl-4-methyl-3-pyrrolin-2-one [11], respectively, which are valuable components for the syntheses of dipyrrinones and linear tetrapyrroles related to bilirubin, biliverdin and phytochrome [1].…”

Homorubins and homoverdins

“…: 60–61 °C (Ref. [26, 42] 61–62 °C); 1 H NMR (300 MHz): δ = 1.25 (3H, t, J = 7.1 Hz), 1.38 (3H, t, J = 7.1 Hz), 2.30 (3H, s), 2.55 (2H, t, J = 7.1 Hz), 3.06 (2H, t, J = 7.1 Hz), 4.10 (2H, q, J = 7.1 Hz), 4.35 (2H, q, J = 7.1 Hz), 9.46 ( 1 H, brs), 9.81 ( 1 H, s) ppm; 13 C NMR (75 MHz): δ = 9.8, 14.1, 14.3, 18.8, 35.3, 60.6, 60.9, 124.5, 126.6, 129.9, 132.1, 160.8, 172.1, 179.5 ppm.…”

Intramolecular hydrogen bonding and linear pentapyrrole conformation

“…1A) of bilirubin [1–3], the yellow pigment of jaundice [4], where intramolecular hydrogen bonding between a dipyrrinone and carboxylic acid proved to be surprisingly effective in rendering bilirubinoids lipophilic, in dictating conformation [5–7], and even in organizing self-assembly [8, 9]. Dipyrrinones are now known to be avid participants in hydrogen bonding [10–13], and absent an available carboxylic acid group, they tend to form intermolecularly hydrogen-bonded dimers [14]. The dipyrrinone chromophore thus constitutes an effective molecular platform for molecular recognition [15].…”

“…The dipyrrinone chromophore thus constitutes an effective molecular platform for molecular recognition [15]. Its proclivity to form intramolecular hydrogen bonds to a carboxylic acid group was explored in numerous linear tetrapyrroles [16–22], with chemically-designed dipyrrinones [10–13, 23–25] and even with a few centrally expanded bilirubin analogs (Fig. 1B) [26–30], some of which (Fig.…”