engleski

1, 3‐Dipolar cycloaddition reaction of 5, 10, 15, 20‐tetra(3‐pyridyl)porphyrin with azomethine ylide

Synthetic and natural porphyrins have a great potential as photosensitisers in photodynamic therapy (PDT). However, for many PDT applications, the main drawback is their low absorption in the red part of the spectrum. Therefore, methods to convert porphyrins into chlorins and bacteriochlorins are constantly sought [1]. Some of these strategies include cycloaddition reactions since porphyrins may act as dienes and dienophiles in Diels‐Alder reaction, and as 1, 3‐dipoles and dipolarophiles in 1, 3‐dipolar cycloaddition reactions [2]. Recently we reported the synthesis of a series of N‐methylated and N‐oxidised pyridylporphyrins and demonstrated high phototoxicity in vitro against various cancer cells with majority of the amphiphilic derivatives [3]. Before extending our research on tissues and in vivo, where the penetration of red light becomes more relevant, we wanted to investigate the reactivity of pyridylporphyrins in cycloaddition reactions. Silva et al. reported 1, 3‐dipolar cycloaddition reactions of meso‐ substitued porphyrins with azomethine ylides, describing higher reactivity of porphyrins with electron‐withdrawing groups [4]. We employed a similar procedure on 5, 10, 15, 20‐ tetra(3‐pyridyl)porphyrin and 5‐(4‐ acetamidophenyl)‐10, 15, 20‐tris(3‐ pyridyl)porphyrin. Azomethine ylide was generated in situ from sarcosine and either paraformaldehyde or benzaldehyde. Several different reaction conditions were applied, including microwave irradiation. In all cases, a very low reactivity was observed and mostly unreacted porphyrin was recovered. Monoadducts formed in all reactions, but could not be separated from other products of, presumably, multiple additions (bisadducts and trisadducts). Finally, a monoadduct from the reaction of 5, 10, 15, 20‐tetra(3‐pyridyl)porphyrin and azomethine ylide, that was generated from sarcosine and paraformaldehyde, in toluene, was isolated after several purifications by column chromatography. The chlorin structure of the monoadduct was confirmed by 1H, 13C NMR and UV/Vis spectroscopy. The product was also analysed by fluorescence spectroscopy. The synthesis, NMR, UV/Vis and fluorescence spectra of the cycloadduct will be presented and described in comparison to its parent compound.

Cycloaddition reaction ; Porphyrin ; Chlorin ; Azomethine Ylide

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