Synthesis of a fluorine analog of hematoporphyrin by ring closure

Benzyl 3,5-dimethyl-2-pyrrolecarboxylate (1) was converted to 4-(2,2,2-trifluoro-1-hydroxyethyl) derivative (2) on treatment with trifluoroacetaldehyde ethyl hemiacetal in the presence of zinc chloride. After protection of the hydroxyl group with a methyl group, 2 was converted to benzyl 4-methyl-3-(2,2,2-trifluoro-1-methoxyethyl)-2-pyrrolecarboxylate (9) and benzyl 5-acetoxymethyl-3-methyl-4-(2,2,2-trifluoro -1-methoxyethyl)-2-pyrrolecarboxylate (10). Both esters were condensed to dipyrrylmethane compound 11, which was debenzylated, decarboxylated and condensed with a bottom half of the porphyrin to give hexafluorohematoporphyrin derivative 14, potentially useful for photodynamic therapy of cancer. Copyright (C) 1996 Elsevier Science Ltd.