Uroporphyrin isomers

A mild procedure which does not involve strong adds, has to be used in the synthesis of pure isomers of unsymmetrically substituted porphyrins from dipyrromethanes. The best procedure having been applied, e.g. in unequivocal syntheses of uroporphyrins II, III, and IV (see p. 251f.), is the condensation of 5,5 -diformyldipyrromethanes with 5,5 -unsubstituted dipyrromethanes in a very dilute solution of hydriodic add in acetic acid (A.H. Jackson, 1973). The electron-withdrawing formyl groups disfavor protonation of the pyrrole and therefore isomerization. The porphodimethene that is formed during short reaction times isomerizes only very slowly, since the pyrrole units are part of a dipyrromethene chromophore (see below). Furthermore, it can be oxidized immediately after its synthesis to give stable porphyrins. 

All acute porphyrias show similar urinary porphyrin patterns with predominant elevation of uroporphyrin and coproporphyrin III isomer in addition, hepta-, hexa-, and especially pentacarboxyporphyrins are increased (see Fig. 7.3.3). 

Porphyrins in plasma are mainly used to distinguish between PCT and pseudoporphyria in patients with chronic hemodialysis. CEP patients also show characteristic elevations with dominance of I-isomers, especially of uroporphyrin and its decarboxylation products, in both plasma and erythrocytes. Plasma porphyrins may be used for follow-up of the patients. 

Porphyrias are inherited or acquired disorders caused by a deficiency of enzymes in the heme biosynthetic pathway. Porphyrin is synthesized in both the erythroblasts and the liver, and either one may be the site of a disorder. Congenital erythropoietic pOTjdtyria, for example, prematurely destroys eythrocytes. This disease results from insufficient cosynthase. In this porphyria, the synthesis of the required amount of uroporphyrinogen III is accompanied by the formation of very large quantities of uroporphyrinogen I, the useless symmetric isomer. Uroporphyrin I, coproporphyrin I, and other symmetric derivatives also accumulate. The urine of... 

Analysis of type I and II isomers of uroporphyrins and coproporphyrins in urine by means of HPLC/FD. According to the disposition the substitutes may adopt around the tetrapyrrol ring of the porphyrin molecule, there are only four possible types of uroporphyrinogens (I, II, III and IV), but in nature only the type I and III uroporphyrinogens exist and, consequently, decarboxylation will only produce coproporphyrinogens I and IIL... 

With this method, a chromotagram is obtained in which the separation and identification can be observed of the isomers of uroporphyrins I and III and coproporphyrins I and III... 

Uroporphyrin, the Nomenclature of Porphyrin Isomers, and the Condensation of Monopyrroles. 298... 

Porphobilinogen when boiled in 0.5 N HCl for 20 minutes is converted to uroporphyrin to the extent of 40%. Cookson and Rimington isolated a crystalline octamethyl ester which had a m.p. of 255°. The major part of this material behaved as uroporophyrin III on paper chromatography, but at least one other isomer was present. To explain the formation of uroporphyrin III from porphobilinogen it may be necessary to assume some branched tri- or tetrapyrrylmethane as an intermediate, perhaps formed by a Corwin condensation vide infra). 

This nomenclature of the isomers is derived from Hans Fischer s nomenclature of the four possible etioporphyrins (f.e., porphyrins having methyl and ethyl side chains). By decarboxylation of uroporphyrin one would obtain an etioporphyrin. There are only four possible ways in which four methyl (Me) and four ethyl groups (Et), one Me and one Et per pyrrole, can be arranged around the ring (Fig. 6). All physiologically... 

In the normal human being the excretion of porphyrins in the urine per day may amount to 100 jug., of which the coproporphyrin I isomer is the main component lesser amounts of coproporphyrin III and only traces of uroporphyrin are excreted. In the feces, per day, about 200-300 jug. of a mixture of coproporphyrin, protoporphyrin, and deuteropor-phyrin are excreted. The traces of deuteroporphyrin are assumed to be formed by the action of the intestinal bacteria on the excreted porphyrins and heme. 

All of the naturally occurring porphyrins and chlorins seem to be derived from the isomer III series. Isomer I uroporphyrin and coproporphyrin have been found, but isomer II has not yet been found. Isomer IV is still chromatographically inseparable from isomer III, and other classic methods of separation would not detect small amounts (10 % ) of the various isomers. The chemical conditions which form a large amount of isomer III are of interest for their possible relation to the biogenesis of these important pigments. 

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