Tetrapyrroles reactions

With the catalysis of strong Lewis acids, such as tin(IV) chloride, dipyrromethenes may aiso be alkylated. A very successful porphyrin synthesis involves 5-bromo-S -bromomethyl and 5 -unsubstituted 5-methyl-dipyrromethenes. In the first alkylation step a tetrapyrrolic intermediate is formed which cyclizes to produce the porphyrin in DMSO in the presence of pyridine. This reaction sequence is useful for the synthesis of completely unsymmetrical porphyrins (K.M. Smith, 1975). 

A sequence of an ozonolysis-PK reaction has been used to convert functionalized cyclohexenes to pyrroles (for example 49 and 50) that are important precursors to natural tetrapyrroles, hemes, and porphyrins ... 

The extremely high sensitivity of bacteriochlorins to various reactions makes their chemistry very difficult. This might also be one reason why methods for the total synthesis of bacteriochlorins had not, until very recently, been developed.13 Total synthesis of a tolyporphin model was reported by Kishi et al.13 using an approach that is very closely related to Eschenmoser s syntheses of hexahydroporphyrins from reduced linear tetrapyrroles by cyclization (see Section 1.5.1). 

The yield of the cyclization step under the influence of a metal template can be increased when the corresponding dialdehyde 19 of the tetrapyrrole 16 is used. The reaction sequence is initiated by insertion of palladium(II) or nickel(II) into the tetrapyrrole to give 20 followed by Michael addition of one acrylaldehyde side chain to the other yielding the macrotetracycle 21 from which in a retro-Michael reaction acetaldehyde is eliminated to give 22. 

Most of the subsequent steps of tetrapyrrole synthesis are identical in plants, animals, and bacteria. The pathway includes synthesis of the monopyrrole porphobilinogen from two molecules of ALA by the action of ALA dehydratase with the elimination of two molecules of water, followed by the assembling of a linear tetrapyrrole hydroxymethylbilane from fonr molecnles of porphobilinogen, ring closure and two modification reactions of side chains. This produces the first tetrapyrrole macrocycle, uroporphyrinogen HI. Therefore, eight molecules of ALA are necessary to form one tetrapyrrole. 

Figure 15.7 The Ni-containing tetrapyrrole F430 of methylCoM reductase and the reaction catalysed by methylCoM reductase (Mcr). (From Shima et al., 2002. Copyright 2002, with permission from Elsevier.)...

Free haem groups are ferroporphyrins (cyclic tetrapyrroles). The first reaction of haem catabolism is the release of iron this is followed by the opening of the ring to produce a linear tetrapyrrole called biliverdin. A molecule of carbon monoxide is released as the ring opens. Biliverdin is converted to bilirubin by reduction. These initial reactions may occur in the liver or in other tissues of the reticuloendothelial system, notably the spleen. 

Pyrrole is very reactive towards electrophiles charge distribution from the nitrogen makes either C-2 (or C-3) electron rich. Thus, a second porphobilinogen acts as the nucleophile towards the methylidene pyrrolium cation in a conjugate addition reaction. It is now possible to see that two further identical steps will give us the required linear tetrapyrrole, and that one more time will then achieve ring formation. 

A ruthenium(VI) nitrido complex containing a tetrapyrrolic macrocycle ligand, [Ru (N)(L)] (82) (H4L = mcio-octamethylporphyrinogen), has been synthesized by the reaction of diphewldiazomethane with [Ru"(L)] , which is prepared from [Ru(cod)(Cl)2] and Na4(L) 4THF. X-ray crystal studies reveal that [Ru (N)(L)] has a Cjv symmetry, and it has the usual saddle conformation, with the metal atom displaced 0.482 A out of the N4 mean plane. The reactivities and redox chemistry of this complex are summarized in Scheme 12 (see also Section 5.6.5.2). 

After the protein part (globin) has been removed, the tetrapyrrole ring of heme is oxidatively cleaved between rings A and B by heme oxygenase. This reaction requires molecular oxygen and NADPH+H", and produces green biliverdin, as well as CO (carbon monoxide) and Fe which remains available for further use (see p. 286). 

The photochemistry of true organomagnesium compounds remains almost completely unexplored. A literature search in preparation of this work found only a few scattered examples of photochemical studies, mostly in relation to Grignard reactions and 1,3-diketonate chelates Similar to the situation with organozinc compounds magnesium tetrapyrrole chelates, i.e. magnesium porphyrins 1, 5,10,15,20-tetraazaporphyrins (por-phyrazines) 2 and phthalocyanines 3 have found more interest. This is primarily related... 

The first step in the two-step pathway, catalyzed by heme oxygenase (HO), converts heme to biliverdin, a linear (open) tetrapyrrole derivative (Fig. 22-25). The other products of the reaction are free Fe2+ and CO. The Fe2+ is quickly bound by ferritin. Carbon monoxide is a poison that binds to hemoglobin (see Box 5-1), and the production of CO by heme oxygenase ensures that, even in the absence of environmental exposure, about 1% of an individual s heme is complexed with CO. 

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