Relation between structure and reactivity in porphobilinogen and related pyrroles

Catalytic diversification upon metal scavenging in a prebiotic model for formation of tetrapyrrole macrocycles

“…The occurrence of the aminoketone and dicarbonyl precursors employed to date is not known, although plausible routes for their formation have been proposed. 16,18 Regardless, the study of the formation of pyrroles equipped for selfcondensation, 73 the formation of tetrapyrroles therefrom, 74,75 the generation of tetrapyrrole structural diversity via combinatorial processes, 19,21 the photooxidation of porphyrinogens, 20,21,76 the partitioning of porphyrins in vesicle membranes, 20,21,77 and the photochemical properties of the resulting porphyrins 20 are all of fundamental interest and together provide a prebiotic model.…”

Abiotic formation of uroporphyrinogen and coproporphyrinogen from acyclic reactants

“…31 Similarly, PBG (0.26 mM) at pH 7.4 and 70 1C for 2 h under anaerobic conditions affords the uroporphyrinogen isomers in B65% yield. 32 Treatment of a given uroporphyrinogen isomer to the acidic macrocyclization conditions results in the statistical distribution of isomers, providing evidence for the thermodynamic stability of the macrocycles. 33 These data indicate the robustness of the macrocyclization process under plausible prebiotic conditions.…”

Aminomethylated Pyrroles: Casting a Spotlight

“…The attempt to apply the same strategy to 3,4-diaryl-substituted pyrrole Mannich bases led only to porphins (76) (R = Ar, R 1 = H); the formation of the related chlorines can not be excluded, but their absence in the reaction mixture has been tentatively explained based on these compounds' high tendency to oxidize to porphins [30]. In the end, it is worth mentioning the research conducted with porphobilinogen with the view of establishing the best reaction conditions for its cyclotetramerization and the resulting products [93], and the effect of the C -4 substituent on its reactivity in uroporhyrinogen formation [94]. Furthermore, under the appropriate conditions, an aminomethylated pyrrole was shown to produce porphyrinogen (80), a hexahydroporphyrin in which the four pyrrole rings are linked through methylene bridges [92].…”

“…A series of β-aminomethylated 1,5-diaryl-2methylpyrroles (94), containing the nitrogen atom of the C-3 substituent in a piperazine and pyrrolidine ring, as part of an acyclic secondary amine such as dimethylamine, or introduced by an aniline or an imidazole substituent with a lesser available nitrogen lone pair of electrons, have been synthesized (Fig. The working hypothesis was that the mentioned pharmacological properties can be ascribed to the presence of non-bonded electrons of a nitrogen atom on a C-3 substituent.…”