Porphyrin, from porphyrinogen

The synthesis of porphyrins from bilanones is free of all symmetry restraints.77 The oxo function is necessary to stabilize the bilane system by its electron-withdrawing effect. The synthesis of porphyrins from the parent bilane without the oxo function and with /3-substituents is possible,54 but the method gives rise to preparative problems due to the sensitivity of these compounds to oxidation, to electrophiles and to acids. Nature circumvents these problems in the cellular environment by exclusion of oxygen, when porphyrinogens, the precursors of porphyrins, are produced from bilanes55 in the course of their biosynthesis. 

Porphyrins were named from the Greek root for purple (porphyra) and owe their color to the conjugated doublebond structure of the tetrapyrrole ring. The porphyrinogens... 

By careful choice of conditions, the simplest dipyrromethane, bis(pyrrol-2-yl)methane, can be obtained directly from pyrrole with aqueous formalin in acetic acid reaction in the presence of potassium carbonate allows 2,5-bis-hydroxymethylpyrrole to be isolated. This diol reacts with pyrrole in dilute acid to give tripyrrane and from this, reaction with 2,5-bis(hydroxymethyl)pyrrole gives porphyrinogen, which can be oxidised with chloranil (2,3,5,6-tetrachloro-p-benzoquinone) to porphine, the simplest porphyrin. 

The most simple method of obtaining a porphyrin on the gram scale is to reflux a dilute benzaldehyde-pyrrole mixture in propionic acid (141°C) for 30 minutes, cool, and filter. A 20% yield of crystalline porphyrin is easy to achieve (Scheme 6.3.1) (Lindsey et al., 1987, 1994 Prathapan et al., 1993). Even pentamers have been obtained by such a reaction in one step from a porphyrin benzaldehyde building block and pyrrole. One just has to carry out the primary formation of the porphyrinogen at a relatively low concentration (10 M) and under nonoxidative conditions, which allow the rearrangement of undesired polymers. Up to 50% of the colorless porphinogens are obtained by acid-catalyzed condensation of pyrrole and aromatic aldehydes under nitrogen. 

Hydroporphyrins. H. are derived from completely unsaturated porphyrins by reduction of the double bonds in the porphine skeleton. The spectrum of naturally occurring H. ranges from the dihydro derivatives chlorin and phlorin(s) through the tetrahydro derivatives bacteriochlorin and isobacteriochlorins, the hexahydro derivatives porphyrinogens and precor-rins to the more highly reduced corphins and factor F430. 

The porphyrin family of compounds are cyclic tetra-pyrolles many of which are intermediates of the heme biosynthetic pathway. The majority of the compounds of interest to the clinical chemist are not in fact porphyrins (with the exception of protoporphyrin) but porphyrinogens in which all four methylene bridges are in the reduced form. The significance of the porphyrins in medicine relates to the class of inherited disorders - the porphyrias -where there is accumulation of the precursors due to an enzyme deficiency in the heme pathway. The clinical presentation of the porphyrias varies from a chronic photosensitivity to severe acute abdominal pain as in acute intermittent porphyria, which may be precipitated by exposure to certain drugs. Characterization of the type of porphyria depends upon the identification of particular patterns of porphyrins in blood, urine, and feces. 

Porphyria cutanea tarda (PCX) has been reported in humans following TCDD exposure (Bleiberg et al. 1964). However, normal urine porphyrin levels have been observed from individuals with severe chloracnegen exposure (Strik 1979). TCDD is a porphyrinogen in animal models and inhibits uroporphyrinogen decarboxylase, the enzyme precipitating PCX in some patients (Mukerjee 1998). 

AUcylidene porphyrins (including oxo-type porphyrinogens) occupy a special category since they are formed through synthetic modifications at both the periphery and the macro-cychc core and can have properties that depart significantly from those reported for the porphyrins. Several macrocycles... 

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