Synthesis of Porphyrin‐Anthraquinone Conjugates as Photosensitizing Agents

Abstract

A series of 5,10,15,20-tetraarylporphyrins covalently linked to anthraquinones belonging to the class of emodin were synthesized following two different pathways. The first method exploits the functionalization of the methyl group in position 6 of O-protected emodins, which can be converted either into a carboxylic acid or into a bromo-methyl derivative. The modified emodins were then bound through amido or ether bonds to one of the tetraarylporphyrins meso phenyl rings bearing an amino or hydroxyl group, respectively. An alternative synthesis exploits the mixed condensation of triacetoxy-emodinaldehyde (or trimethoxy-emodinaldehyde) with pyrrole in the presence of variable amounts of benzaldehyde, thus affording two similar 5-emodin-10,15,20-triphenylporphyrins differing from one another in the emodin hydroxyl group protection. These compounds are characterized by direct conjugation of the emodin moiety to the tetrapyrrolic ring. Preliminary experiments were performed in vitro on the human colon adenocarcinoma cell line HCT116 to evaluate the photocytotoxicity of the new compounds.

Facile Synthesis of a Phototoxic Monofunctionalized Tetraarylporphyrin as Scaffold for Porphyrin-Quinone Conjugates

“…The reported photoactivation of the anthraquinone moiety sensitized by the conjugated tetraarylporphyrin [12] has shown promise for the development of oxygenindependent PDT agents. To further explore this phenomenon, we conjugated porphyrin 1 with the anthraquinone aminoderivative 8 [15] (Scheme 2) and proved the structure of conjugate 3 by 1 H NMR and HRMS.…”

“…[2][3][4][5][6][7][8] Despite the recent advancements in these procedures, monofunctionalization of porphyrins remains a synthetic challenge. [9] The known phenomena of reductive activation of quinone anticancer drugs, [10] photoactivation of anthraquinones as DNA-cleaving agents, [11] and phototoxicity of porphyrin-anthraquinone hybrids [12] make facile conjugation of quinones and monofunctionalized porphyrins via adjustable linkers a possible approach to the design of oxygen-independent photodynamic therapy (PDT) systems. Here we report synthesis of the monocarboxylated porphyrin 1 and demonstrate its synthetic value as a building block for the design of porphyrin-containing systems including, but not limited to, PDT agents.…”

Phenyl Substituted Porphyrins. Part 5. Acylation of Aminophenylporphyrins

“…[22] As a catalyst, N,N-dimethylaminopyridine (DMAP) is generally used. [21][22][23]25] The current paper covers our research on optimal acylation conditions affording maximal yield of acylamidophenylporphyrins.…”

“…The common acylation agents include various carboxylic acid derivatives: chloroanhydrides, [2][3][4][5][6][7][8][9][10][11][12][13] anhydrides, [14][15][16][17][18][19] and carboxylic acids themselves as well. [20][21][22][23][24][25][26] In the latter case the common solvents are methylene chloride, [24,26] THF [22,23,25] and chloroform. [20,21] The reaction temperature varies from 0 ºС to ambient temperature.…”

“…[20,21] The reaction temperature varies from 0 ºС to ambient temperature. [20][21][22][23][24][25][26] It should be noted that when carboxylic acids are employed for acylation, activating agents must be added: N,N'-dicyclohexylcarbodiimide, [20,21,[24][25][26] 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDAC) [22,23] or mixtures of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) with N-methylmorpholine. [22] As a catalyst, N,N-dimethylaminopyridine (DMAP) is generally used.…”