32562-61-1

Treatment of hematoporphyrin IX dimethyl ester (7) with tetrapropylammonium perruthenate (Pr(n)4N(RuO4) and N-methylmorpholine N-oxide affords a high yield of the separable monoacetylmono(1-hydroxyethyl)-deuteroporphyrin isomers 5 and 6. Proton NMR NOE experiments and chemical transformations involving specific individual deuteration at the 1- and 3-methyls and 2- and 4-vinyls are used to characterize the isomers.

The N-protonations in the deutero, hemato, meso and protoporphyrin IX dimethyl esters (DME) were investigated by spectrophotometric titrations using HCl as the acid and methanol as the solvent. Two spectroscopically different protonated species were observed for each porphyrin DME in addition to the neutral form. These were assigned to the N-protonated monocation and dication. There were no difficulties encountered in observing the monocation formation in the HCl-MeOH system. Very sharp isosbestic points were characteristic of each protonation stage. The pK3 values for the porphyrins in the above order were 3.23, 4.70, 2.93 and 3.37; the pK4 values were 2.48, 2.62, 2.41 and 2.64, respectively. For all porphyrins studied, no further spectral changes were observed after the dication was completely formed. This was interpreted as indicating that the formation of more highly protonated species is not possible in fullydelocalized porphyrins possessing the 18 π-electron [18]diazaannulene delocalization pathway. When the titration was performed on the free dicarboxylic acid porphyrins, aggregation obscured the first protonation step and no clear monocation spectrum could be distinguished. However, also in that case the titration ended up to a UVvis spectrum typical of the dication and the effect of aggregation on the pK4 values was negligible. The UVvis spectrometric parameters are given for the neutral forms and for the protonated species of the porphyrin DMEs. The results are discussed in terms of the NH tautomerization connected to the π-electron delocalization pathway (aromaticity), which tends to hinder outofplane distortions in the porphyrin plane, and in terms of solvation and counterion stabilization of the protonated forms.

The present invention relates to a process for preparing a porphyrin of formula (I), optionally in the form of a salt with an alkali metal and/or in the form of a metal complex: in which: R and R′ are as defined in claim 1, comprising: a step of condensation, in an acidic medium, between a dipyrromethane of formula (II): in which R′b is as defined above for (I), and a dipyrromethane of formula (III): in which R″ is as defined in claim 1, and also the compounds of formula (III).

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Porphyrin carboxylic acids and 1-hydroxyethyl groups can be rapidly esterified and etherified using alcohol/trialkyl orthoformate/strong acid mixtures; addition of water to the reagent permits esterification only.

A mixture of acetic and sulfuric acids converts haematoporphyrin into a complex mixture of porphyrins of which the main product has been characterized as the diacetate (1g).Other compounds identified in the reaction mixture were the known vinylporphyrins (1b-d), (1h) and (1i) and the isomeric monoacetoxyethyl(monohydroxyethyl)porphyrins (1l) and (1m).Analysis of the reaction mixture was complicated by the presence of 1'-ethoxyethyl derivatives (1e) or (1f), (1j) and (1k) which presumably arose by solvolysis of the corresponding acetate with ethanol present in the chloroform used for the the chromatographic separation.

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