Synthesis of porphyrin c-type compounds from protoporphyrinogen

Abstract

The products formed in the reaction of proto-porphyrinogen with L-cysteine, mercaptoethanol, reduced glutathione and thioglycollic acid have been purified and characterized by paper chro-matography. L-Methionine and S-methyl-L-cysteine do not react with protoporphyrinogen or haematoporphyrinogen. No reaction occurred between the above mercaptans and protoporphyrin, protohaem, meso-porphyrin, deuteroporphyrin, coproporphyrin, uroporphyrin (or their corresponding porphyrinogens), haematoporphyrin, haematohaem or diacetyldeuteroporphyrin. However, a thioglycollateporphyrin could be prepared from haematoporphyrin and thioglycollic acid in the presence of a condensing agent. Haematoporphyrinogen reacted readily with thiol compounds, but evidence was obtained that haematoporphyrinogen is probably not an intermediate in those reactions in which protoporphyrinogen is the starting material. The porphyrin c-like adduct formed from protoporphyrinogen and L-cysteine has been crystallized and its spectral properties in the visible and infrared regions have been recorded. Cleavage of the adduct with silver sulphate yields cysteine and a haematoporphyrin. On the basis of chromatography, visible and infrared spectral properties, rate of conversion into protoporphyrin and oxidation to 2,4-diacetyldeuteroporphyrin it is identical with authentic haematoporphyrin. This establishes that the sulphur atoms are attached to the a-carbon atoms of the vinyl side chains. Iron has been incorporated into the adduct by two different methods to produce a c-type haem. The synthesis of isohaematoporphyrin [2,4-di- [beta]-hydroxyethyl)-l,3,5,8-tetramethylporphin- 6,7-dipropionic acid] from 2,4-diformyldeuteroporphyrin is described. 2,4-Diacetaldehydodeutero-porphyrin, an intermediate in this synthesis, and its oxime were characterized by their spectral properties in the visible and infrared regions.