Reactions between pyridoxal and L-amino acids in the absence and in the presence of zinc(II): The role of the metal in the prevention of Pictet-Spengler cyclization

Attempts to obtain Schiff bases from the reactions of pyridoxal with L-histidine and L-tryptophan resulted in Pictet-Spengler cyclization, with formation of potassium 4-[3-hidroxy-5-(methylpyridin-4-yl]-4,5,6,7-tetrahydropyrido[ 3,4-c]imidazole-6-carboxylate (1) and 1-[2-methyl-3-hydroxy-5-(hydroxymethyl)pyridine-4-yl]-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid (2). Investigations on the diastereoselectivity of the reactions by means of NOESY and ROESY bidimensional NMR spectra of 1 and 2 revealed the presence of the cis isomer in both cases. Theoretical calculations of the reactions' free energies showed that only the formation of the cis isomer of 1 is thermodynamically favored, in accordance with the experimental results. However, the formations of both cis and trans isomers of 2 are thermodynamically favored, suggesting that other factors might have been responsible for the experimental detection of only the cis isomer. One-pot reactions of pyridoxal with L-histidine or L-tryptophan in the presence of zinc acetate or zinc chloride resulted in the formation of [Zn-2(Pdx-LHis)(2)(H2O)(2)]center dot 4H(2)O (C1) and [Zn(Pdx-L-Trp)(H2O)]center dot 1.5H(2)O (C2) complexes in which Pdx-L-His and Pdx-L-Trp are the pyridoxal-L-histidine and pyridoxal-L-tryptophan Schiff bases, respectively, indicating that the metal prevents cyclization upon coordination of the Schiff base intermediate.

Automated summary

Attempts to obtain Schiff bases from the reactions of pyridoxal with L-histidine and L-tryptophan resulted in Pictet-Spengler cyclization, leading to the formation of specific cyclic compounds. The diastereoselectivity of the reactions was investigated and the cis isomer was found to be present in both cases. The theoretical calculations of the reactions' free energies and the formation of complexes with zinc indicated the thermodynamic preferences and the prevention of cyclization.