Scope and limitations of two model prebiotic routes to tetrapyrrole macrocycles

New Journal of Chemistry Pub Date: 2016-07-05 DOI: 10.1039/C6NJ01423B

Abstract

Two routes have been proposed as chemical models for the prebiogenesis of tetrapyrrole macrocycles. In each case, the formation of a pyrrole equipped for self-condensation has proved to be the key step, given that the pyrrole self-condensation readily affords porphyrinogen macrocycles. The scope of the two routes is investigated herein. In the first route, a β-ketoester bearing a 4-phosphonooxy substituent was found to react with δ-aminolevulinic acid (ALA) at lower temperature (35 °C) than that of the 4-methoxy substituent (90 °C) to give the corresponding tetraalkyl-tetraester porphyrin, but eight other 4-substituents (Cl-, HO-, AcO-, AcS-, NCS-, MeS-, chloropyridinium-, and morpholino-) failed at 60 or 90 °C. In the second route, reaction of 1,5-dimethoxypentane-2,4-dione (bearing an acetic acid substituent at the 3-position) with 1-aminoacetone gave the corresponding octaalkylporphyrin in a yield comparable to that of the α-aminoketone ALA. Each pyrrole in the resulting porphyrin bears one methyl group and one acetic acid group, thereby constituting a des-methyl homologue of coproporphyrin. The results delineate the features of structure-directed reactions and highlight the limitations of such reactions where no explicit enzyme-like catalyst is present to guide the outcome.

Graphical abstract: Scope and limitations of two model prebiotic routes to tetrapyrrole macrocycles
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