How are pyrrole-2-carboxaldehydes (Py-2-C) synthesized chemically?

Py-2-C derivatives can be synthesized chemically by the strong acid-catalyzed condensation of glucose and amino acid derivatives in vitro. This process involves the formation of various intermediates and products, including N-substituted-5-methoxymethyl-2-formyl-pyrroles.

From: "Pyrrole-2-carboxaldehydes: Origins and Physiological Activities", Molecules 2023, 28(6), 2599;

The chemical synthesis of Py-2-C involves the condensation of glucose with alkylamines under acidic conditions, such as acetic acid catalysis. This reaction produces N-substituted-5-methoxymethyl-2-formyl-pyrroles in low yields. The proposed mechanism includes the formation of 3-deoxy-D-glucose, followed by an attack of the alkylamine on the enol site, leading to the formation of a dihydropyrrole, which then undergoes dehydration to form the final Py-2-C product. This synthetic route suggests that similar reactions could occur under physiological conditions over time.