Synthetic and biosynthetic studies of porphyrins: III. Structures of the intermediates between uroporphyrinogen-III and coproporphyrinogen-III: Synthesis of fourteen heptacarboxylic,hexacarboxylic, and pentacarboxylic porphyrins related to uroporphyrin-III

Four heptacarboxylic, six hexacarboxylic, and four pentacarboxylic porphyrins related to uroporphyrin-III by decarboxylation of one, two, or three of the acetic acid side chains have been synthesised as their methyl esters by application of the MacDonald or b-oxobilane methods, as appropriate. Comparison (mixed mp, “mixed” nmr spectra, and hplc) of the synthetic materials with the methyl esters of hepta-, hexa-, and pentacarboxylic porphyrins isolated from natural sources showed that the structures of the latter corresponded to the D-ring methyl, the DA-dimethyl, and the DAB-trimethyl analogs of uroporphyrin-III. Because the naturally occurring porphyrins arise by oxidation of intermediate porphyrinogens, we conclude that the enzymic decarboxylation of uroporphyrinogen-III to coproporphyrinogen-III takes place in a preferred sequential clockwise fashion (both in normal and abnormal metabolism) starting with the acetic acid moiety on the D-ring and followed by those on the A, B, and C rings.