Protoporphyrin synthesis

In clinical cases, coproporphyrin I is found to be excreted in increased amounts in conditions of rapid blood regeneration. This fact has been suggested to favor the hypothesis that coproporphyrin I is a by-product of normal protoporphyrin synthesis. Coproporphyrin III is said to predominate over coproporphyrin I in the toxic conditions such as lead poisoning and in aplastic anemias. 

Protoporphyrin-IX, N-methyl-, 4, 396 Protoporphyrins, 4, 382 photooxygenation, 4, 402 Prototropic tautomerism polyheteroatom six-membered rings, 3, 1055 Prozapine properties, 7, 545 Pschorr reaction carbolines from, 4, 523 dibenzazepines from, 7, 533 dibenzothiophenes from, 4, 107 phenanthridines from, 2, 433 Pseudilin, pentabromo-synthesis, 1, 449 Pseudoazulene synthesis, 4, 526 Pseudobases in synthesis reviews, 1, 62 Pseudocyanines, 2, 331 Pseudothiohydantoin synthesis, 6, 296 Pseudouracil structure, 3, 68 Pseudoyangonin IR spectra, 3, 596 Pseudoyohimbine synthesis, 2, 271 Psicofuranine biological activity, 5, 603 as pharmaceutical, 1, 153, 160... 

The synthesis of porphyrins from monopyrrolic, dipyrrolic, tripyrrolic and tctrapyrrolic precursors requires, even for an experienced porphyrin chemist, a substantial amount of time and effort to accomplish. As an alternative to these total synthetic routes, nature provides a source of prefabricated porphyrins. Among the several porphyrins which can be isolated from natural material,s the red blood pigment heme, protoporphyrin dimethyl ester81 b and hemato-porphyrin, both derived from heme, are the only compounds which can be obtained in sufficient amounts. Heme is available in almost unlimited amounts from slaughter-house waste. From 1 L of blood ca. 1 g of heme can be isolated.81 b Currently, heme is offered commercially by chemical retailers at a relatively low price so that is cheaper to buy hemin than to perform a self-isolation in the laboratory. 

The modification of porphyrins leading to isobacteriochlorins by C —C-bond formation is important to obtain a wide range of structurally different isobacteriochlorins which can then be further transformed. Protoporphyrin, deutoroporphyrin and hematoporphyrin (readily accessible from red blood pigment) are interesting and useful starting materials in the synthesis of isobacteriochlorins. 

The final step in heme synthesis involves the incorporation of ferrous iron into protoporphyrin in a reaction catalyzed by ferrochelatase (heme synthase), another mitochondrial enzyme (Figure 32-4). 

It is possible that lead s interference with heme synthesis may underlie the effects on vitamin D metabolism. Evidence that lead affects heme synthesis in the kidney was presented in the section on hematological effects. In addition, apparent thresholds for the effects of lead on renal vitamin D metabolism and for erythrocyte protoporphyrin accumulation are similar. 

The regulatory network of IRPs appears also to connect the synthesis of protoporphyrin IX in erythroid cells, and of certain mitochondrial iron-sulfur proteins to iron bioavailability (reviewed in Hentze and Kuhn, 1996). mRNAs encoding erythroid... 

The second methodology involves direct introduction of glycosylated moieties onto a suitably functionalized meso-arylporphyrin scaffold, accessible from a natural source (protoporphyrin-IX) or by total synthesis. Several O-,133,145,146 S-,147 and N-glycoporphyrins148 (125-129) have thus been prepared (Fig. 12). Moreover, in order to explore the influence of the clustered peripheral saccharides around the porphyrin scaffolds, and to evaluate their photophysical properties, the synthesis of dodecavalent porphyrins bearing four trivalent glycodendrons via amide ligation (129) has been achieved.149... 

The Stille Pd-catalyzed cross coupling has been employed in the synthesis of modified porphyrins [54, 55, 82]. For example, the union of dOialoporphyrins with tri-n-butylvinylstannane affords protoporphyrin IX in excellent yield [82]. 

The starting material for the synthesis was the iron compound of deuteroporphyrin in which c and d = H. By means of the Friedel-Crafts reaction (SnCl4 in place of A1C13), acetyl groups were introduced at c and d, the diketone formed was reduced to the glycol (haemato-porphyrin, c and d = CHOH.CHs), and the latter converted into protoporphyrin with elimination of water. 

A similar reservation applies to the need to remove ligand precursors or byproducts from the support. This is a particular issue in relation to intrazeolite com-plexation reactions in which the corresponding homogeneous synthesis is less than quantitative. Another difficulty relates to estabUshing the efficacy of ligand synthesis within a zeoUte. Thus, for example, although several reports of the syntheses of metal porphyrin complexes within zeolites have appeared, the ligands are, in fact, domed porphodimethenes (diameter -14 A), or protoporphyrins [138,... 

Lead ions also inhibit ferrochelatase-cataiyzed insertion ofFe into protoporphyrin iX in the final step of heme synthesis. 

Committed step in heme synthesis, its coenzyme, and inhibitor The committed step in heme synthesis is the formation of 5-amlnolevulinic acid (ALA). The reaction, which requires pyridoxal phosphate as a coenzyme, is catalyzed by ALA synthase. The reaction is inhibited by hemin (the oxidized form of heme that accumulates in the cell when it is being under-used). The conversion of protoporphyrin IX to heme, catalyzed by ferrochelatase, is inhibited by lead. 

Methods using condensations of two dipyrrolic units suffer from inherent symmetry restrictions, though these are of course less serious than those involved in the use of monopyrrole tetramerization. Thus the routes through dipyrroles are limited to synthesis of porphyrins which are centrosymmetrically substituted (by way of self-condensation of a suitably activated dipyrrole), or to porphyrins which possess subunit symmetry in one or both halves of the molecule. It is very fortunate that this latter restriction is not serious for the synthesis of porphyrins from natural materials because rings c and d of uroporphyrin-III, coproporphyrin-III and protoporphyrin-IX (Table 1), for example, are symmetrically substituted about the C-15 atom. 

Chlorophyll. The pathway of chlorophyll synthesis has been elucidated through biochemical genetic studies of Rhodobacter spheroides y]7 118a which produces bacteriochlorophyll, from studies of cyanobacteria,419 420 and from investigations of green algae and higher plants,421 which make chlorophyll a. The first step in the conversion of protoporphyrin IX into chlorophyll is the insertion of Mg2+ (Fig. 24-23, step a). 

---