STRATEGY FOR THE SYNTHESIS OF NEW WATER-SOLUBLE UNSYMMETRICAL SUBSTITUTED HETARYLPORPHYRINS

A strategy for the directed synthesis of several asymmetric water-soluble porphyrins with fragments of small heterocyclic molecules on the periphery of the macrocycle has been developed, which allow tuning to certain biotargets and regulating the hydrophobic/ hydrophilic balance. Organometallic catalysis methods were used to obtain a covalent bond between heterocyclic molecules and porphyrin macrocycle. It was found that the hetarylation of 5-(4ʹ-bromophenyl)-10,15,20-tri(pyridin-3ʹ-yl)porphine by heteroarenes containing ‘acidic’ C-H bonds, such as benzoxazole, benzothiazole, 1,3,7-trimethylxanthine, and N-methylbenzimidazole is carried out in the presence of the Pd(OAc)2/Cu(OAc)2/PPh3/K2CO3 catalytic system in boiling toluene. The porphyrin with guanine residue was obtained using a catalytic system based on copper (II) and palladium (II) acetate in boiling acetic acid, and the macrocycle with the adenine residue was obtained using a catalytic system based on palladium (II) acetate and copper (I) iodide in boiling water. To prepare a porphyrin with an indole residue, 4-bromobenzaldehyde was first modified using a PdCl2-based catalytic system based palladium chloride. We have proposed an alternative procedure for the preparation of this substituted benzaldehyde. Next, the corresponding porphyrinogen was obtained by mixed-aldehyde condensation with pyrrole in boiling propionic acid with the addition of propionic anhydride under argon atmosphere. Oxidation of the porphyrinogen with air oxygen gave the desired indole-substituted porphyrin. All porphyrins were separated and purified by column chromatography on aluminium oxide (activity grade III according to Brockmann). To make the hetaryl porphyrins water soluble, they were subjected to quaternization with methyl iodide on pyridyl moieties in boiling DMF. For citation: Syrbu S.A., Kiselev A.N., Lebedev M.A., Kibireva Y.E. Strategy for the synthesis of new water-soluble unsymmetrical substituted hetarylporphyrins. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2025. V. 68. N 7. P. 48-56. DOI: 10.6060/ivkkt.20256807.7237.