Synthesis of functionalized chlorins sterically-prevented from self-aggregation

•Synthesis of six chlorins sterically self-prevented from aggregation is described.•A vinyl porphyrin and p-substituted maleimides were used as building blocks.•Amphiphilic chlorins were obtained after functionalizations.•These new chlorins have proven to be good candidates for PDT studies.

The synthesis of six new regioisomeric chlorin derivatives sterically-prevented from self-aggregation is described. The compounds were prepared by the Diels–Alder reaction between protoporphyrin IX dimethyl ester, and N-[p-(1,3-dithiolan)phenyl]maleimide and N-(p-formylphenyl)maleimide. The protopophyrin IX dimethyl ester was synthesized in 2 steps from natural hematoporphyrin using a modified procedure from literature, and the substituted maleimides were conveniently synthesized, aiming at producing formyl-chlorins for subsequent functionalization with amphiphilic groups. The Diels–Alder reactions were systematically studied in order to establish optimized conditions for the cycloadditions.The regioisomers were fully characterized and the aggregation studies were performed by NMR, UV–Vis spectroscopy, and also HRMS (ESI-TOF and MALDI-TOF). Preliminary evaluations on the photosensitizing activities and amphiphilicity were carried out indicating that these new compounds are potential candidates, to be studied in more advanced tests of Photodynamic Therapy (PDT). This work represents on advance on our previous study, with respect to these new structures, their photophysical properties and amphiphilicity.

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