Synthesis of Formyl(2,2,2-trifluoro-1-hydroxyethyl)deuteroporphyrins and Their Derivatization to Porphyrin Derivatives with Elongated Side-Chains.

Abstract

We previously synthesized 3- and 8-mono, and 3, 8-bis(2, 2, 2-trifluoro-1-hydroxyethyl)deuteroporphyrin dimethyl esters (2-4) by Friedel-Crafts reaction of deuteroporphyrin dimethyl ester (1) with trifluoroacetaldehyde, and trifluorohematoporphyrin analogs (5 and 6) by acetylation of 2 and 3 followed by reduction. These fluorine analogs of natural porphyrins have interesting biological properties; some of them accumulate selectively in certain tumor cells. In order to introduce larger substituents at the 8- or 3-position of 2 and 3, 2 and 3 were converted in several steps to 8- and 3-formyl derivatives (13 and 14), respectively. These were treated with vinylmagnesium bromide to give 8- or 3-(1-hydroxy-2-propenyl) derivatives (15 or 16). Further, reaction of 7 or 8 with the enol ether of 2-octanone gave the 8- or 3-(3-oxo-1-nonenyl) compounds (17 or 18). The affinities of the porphyrin derivatives, obtained by hydrolysis of the above porphyrin esters, for tumor tissues were examined. Among them, the porphyrin obtained by hydrolysis of 16 was found to accumulate in liver cancer transplanted in nude mice to a greater extent than hematoporphyrin.