The Porphobilinogen Conundrum in Prebiotic Routes to Tetrapyrrole Macrocycles
8
Citation
72
Reference
10
Related Paper
Citation Trend
Keywords:
Porphobilinogen
Tetrapyrrole
Enamine
Pyrrole
Chemical Biology of the Nitrogen Heterocycle Porphobilinogen in Tetrapyrrole Macrocycle Biosynthesis
This final chapter analyzes the chemical logic in the tetrapyrrole biosynthetic pathway to heme B with focus on how the aminomethylpyrrole heterocycle of prophobilinogen is assembled and then utilized to build the tetrapyrrole macrocycles of heme and chlorphyll. Enzymatic steps include the formation of the porphobilinogen building block by aldol condensative dimerization of 4-aminolevulinate, its chain extension to the linear tetrapyrrole hydroxybilane, and its enzyme-directed cyclization to uroporphyrinogen III. Subsequently the tailoring of the macrocycle periphery involves loss of the six of the eight peripheral carboxylates as CO2, six-electron oxidation of the macrocycle to a 20 π-electron system and ferrous iron insertion to give heme B. The aminopyrrole framework of porphobilinogen serves both as electrophile via a C2 azafulvene form and as a nucleophile at C5. Fourteen of the starting 48.
Tetrapyrrole
Porphobilinogen
Hexacoordinate
Porphobilinogen deaminase
Cite
Citations (0)
Porphobilinogen synthase
Porphobilinogen
Porphobilinogen deaminase
Cite
Citations (4)
Abstract Durch säurekatalysierte Kondensation der einfachen Monopyrrole (III) bzw. (VII), die der Porphyrin‐Biosynthesevorstufe Porphobilinogen strukturverwandt sind, lassen sich in hochselektiver Reaktion die bisher unbekannten Porphyrinoctacarbonsäuren (Va) bzw. (Vc) ‐ charakterisiert als Methylester (Vb) bzw. (Vd) ‐ darstellen.
Tetrapyrrole
Porphobilinogen
Cite
Citations (1)
Tetrapyrrole
Porphobilinogen
Condensation reaction
Cite
Citations (27)
Porphobilinogen
Tetrapyrrole
Cite
Citations (70)
A short synthesis of the tetrapyrrole pigment precursor porphobilinogen (1) has been developed which requires only readily available and inexpensive starting materials, and which is amenable to introduction of isotopic labels at key positions required for biosynthetic studies.
Porphobilinogen
Tetrapyrrole
Porphobilinogen synthase
Cite
Citations (27)
Changes in some of the key intermediates and procedures used in our earlier total synthesis of porphobilinogen from pyrrole that improve the yield to 11% are reported. Ethyl pyrrole-3-acetate was formylated by the Vilsmeier–Haack method and then iodinated. The desired 2,3,4-substituted pyrrole isomer was isolated in moderate yield and, after conversion of iodide to acrylate and aldehyde to aldoxime, reduction and work-up afforded porphobilinogen lactam ethyl ester. Hydrolysis of the latter gave porphobilinogen in ten steps from pyrrole.
Porphobilinogen
Pyrrole
Methyl iodide
Cite
Citations (25)
A synthetic strategy has been developed which enables pyrrole to be used as the starting material for the synthesis of 2,3,4-trisubstituted pyrroles of the type used to construct porphyrins. The total synthesis of porphobilinogen has been accomplished as a demonstration of the applicability of the approach.
Porphobilinogen
Pyrrole
Cite
Citations (33)
Tetrapyrrole macrocycles (e.g., porphyrins) have long been proposed as key ingredients in the emergence of life, yet plausible routes for forming their essential pyrrole precursor have previously not been identified. Here, the anaerobic reaction of δ-aminolevulinic acid (ALA, 5–240 mM) with 5-methoxy-3-(methoxyacetyl)levulinic acid (1-AcOH, 5–240 mM) in water (pH 5–7) at 25–85 °C for a few hours to a few days affords uroporphyrinogen, which upon chemical oxidation gives uroporphyrin in overall yield of up to 10%. The key intermediate is the α-methoxymethyl-substituted analogue of the pyrrole porphobilinogen (PBG). Reaction of ALA and the decarboxy analogue of 1-AcOH (1-Me) gave coproporphyrinogen (without its biosynthetic precursor uroporphyrinogen as an intermediate); oxidation gave the corresponding coproporphyrin in yields comparable to those for uroporphyrin. In each case a mixture of porphyrin isomers was obtained, consistent with reversible oligopyrromethane formation. The route investigated here differs from the universal extant biosynthetic pathway to tetrapyrrole macrocycles, where uroporphyrinogen (isomer III) – nature's last common precursor to corrins, heme, and chlorophylls – is derived from eight molecules of ALA (via four molecules of PBG). The demonstration of the spontaneous self-organization of eight acyclic molecules to form the porphyrinogen under simple conditions may open the door to the development of a chemical model for the prebiogenesis of tetrapyrrole macrocycles.
Tetrapyrrole
Levulinic acid
Porphobilinogen
Uroporphyrinogen III decarboxylase
Pyrrole
Structural isomer
Cite
Citations (35)
Porphobilinogen
Tetrapyrrole
Cite
Citations (60)