Tetrapyrroles

This is a general term for porphyrins and bilane derivatives (cyclic and open-chain tetrapyrroles, respectively), centered aronnd a nnmerically limited nnmber of natnral products. Other lUPAC parent skeletons are phorbine, corrin, chlorin, and phthalocyanine (synthetic). See Pure Appl. Chem., 59, 779-782,1987, for the nnmbering of these skeletons. 

The parent porphyrin system is called porphyrin (lUPAC) or porphine (CAS). In the old litera-tnre, the so-called Fischer nnmbering may be enconntered. 

Propionic acid bacteria can synthesize a number of tetrapyrrole compounds corrinoids, heme, heme-containing enzymes, cytochromes, and linear tetrapyrroles. Biosynthesis of tetrapyrroles by all microorganisms starts with the formation of 5-aminolevulinic acid (ALA) (Corcoran and Shemin, 1957) and proceeds through the formation of porphobilinogen (PBG) and uroporphyrinogen (UPB) (Fig. 4.19A). Of the four possible isomers of uroporphyrinogenes, only the derivatives of UPB III are found in nature. 

In coenzymes the upper ligand (Co-P) is represented by 5 -deoxyadenosyl, the resulting adenosylcobalamin (AdoCbl) has a molecular mass of 1600 D (Fig. 4.20B). Actually, the upper ligand can vary widely with no effect on the association with proteins or on the biological activity in 

The corrin ring and the nucleotide moiety are synthesized only by bacteria and some algae, but the cobalt-binding p-ligands can be introduced by some enzymatic systems in animals and humans. The synthesis of precursors in adequate amounts is often impaired, that is why microorganisms, in addition to the biologically active forms, also contain incomplete forms of corrinoids, mainly those in which the nucleotide moiety is lacking cobyric acid, cobinamide, cobinamide-P and cobinamide-GDP. Under conditions unfavorable for the synthesis of the nucleotide moiety incomplete forms may predominate, especially cobinamide. The content of complete forms increases in old (or aerated) cultures at the expense of incomplete forms. 

arabinosum and the bacteria that live in the gut of humans and animals synthesize mostly the purine-containing cobamides. If DMB is added to the feed, then the synthesis of cobalamins in the stomach of animals increases (Rickard et al., 1975). The finding of incomplete corrinoids in various bacteria and algae (Neujahr and Frires, 1966) shows that their biosynthesis may proceed with difficulty. Cobinamide, pseudo-vitamin B, factor A and factor III can act as growth factors for microorganisms if they contain a nucleotide, they are also active in enzymatic reactions in animals. 

A highly unusual porphynoid (117), named tunichlorin, was isolated from the Caribbean tunicate Trididemnum solidum from which didemnins (Section VIII), anticancer cyclopeptides, had previously been obtained 

From the Japanese bryozoan Bugula dentata, an antimicrobial blue pigment (121) was isolated (111) and found to be identical with a tetrapyr-role previously isolated from a mutant strain of Serratia marcescens (112). The color of the bryozoan B. dentata is unusually dark blue, suggesting that the pigment 121 is ubiquitously present in the animal. Whether compound 121 is biosynthesized by the bryozoan itself or by an associated microorganism or derived from food sources such as prodigiosin-producing bacteria is still unknown. 

173-Cyclopheophorbide enol (122) a nonmetalated chlorophyll a derivative was isolated from a New Zealand sponge (Darwinella oxeata) and its structure determined by X-ray measurements (113). Although 132,173-cyclopheophorbide enol (122) was first isolated from natural sources, it had previously been synthesized during a study of ring E enolization of chlorophyll derivatives (114). A new pheophorbide a-related compound named chlorophyllone a (123) was isolated from extracts of the short-necked clam Ruditapes philippinarum (115). Compound 123 exhibits antioxidative activity. 

All pyrrole units of the porphyrin system are partially hydrogenated in the C19 structure of corrin 6. Two pyrrole rings are directly linked at the expositions and not via a methine group. 

Porphyrins form a planar macrocycle that contains a conjugated, cyclic delocalized system of 22 n-electrons [17]. 18 Electrons can be assigned to the perimeter of a l,16-diaza[18]annulene, an arrangement which is also found in the chlorin and bacteriochlorin systems. Porphyrins and chlorins are intensely coloured (1 red to violet, Amax 500-700 nm 2-4 green, 600-700 nm). 

The reactions of porphyrins arise from the aromatic annulene character and the amphoteric behaviour of the pyrrole units which exist as IH- or 2//-structures. Accordingly, porphyrins form tetradentate chelate complexes 7 with many cations, and as weak bases pKaj 7, pKa2 4) they can be protonated to give dications 8. 

Porphyrins and their metal complexes can be substituted by electrophiles, e.g. by deuteriation, nitration and ViLSMElER formylation at the methine and pyrrole C-atoms. 

Reduction of porphyrins by catalytic hydrogenation leads to phlorins and with diimides, chlorins are obtained porphyrinogens are formed with sodium borohydride, Na/Hg or by catalytic hydrogenation under drastic conditions. 

Among natural products in this category, vitamin B12 and chlorophylls in particular have been extensively examined using the newer ionization techniques. Again the emphasis has been on model studies on known structures though some of these have relevance to aspects of their biosynthesis or the mechanism of their biological activities. 

The analysis of intact cobalamines by mass spectrometry requires desorption ionization methods and the first spectrum of vitamin B12 (20) containing molecular ion species was obtained in 1978 using FDMS 86), By a careful analysis of the relative abundances of the and C-containing 

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Figure B2.1.7 Transient hole-burned speetra obtained at room temperature with a tetrapyrrole-eontaining light-harvesting protein subunit, the a subunit of C-phyeoeyanin. Top fluoreseenee and absorption speetra of the sample superimposed with die speetnuu of the 80 fs pump pulses used in the experiment, whieh were obtained from an amplified CPM dye laser operating at 620 mn. Bottom absorption-diflferenee speetra obtained at a series of probe time delays.

Figure B2.1.10 Stimulated photon-echo peak-shift (3PEPS) signals. Top pulse sequence and iuterpulse delays t and T. Bottom echo signals scaimed as a fiinction of delay t at tluee different population periods T, obtained with samples of a tetrapyrrole-containing light-harvesting protein subunit, the a subunit of C-phycocyanin.

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). 

The Ni and V concentrated into the vacuum resid appear to occur in two forms. Erom 10 to 14% of each of these two metals can be distilled in the 565—705°C boiling range, where they exhibit the strong visible Soret bands associated with the porphyrin stmcture. This tetrapyrrole stmcture (48,49), possibly derived from ancient chlorophyll, has been confirmed by a variety of analytical techniques. 

Bile Pigments. The oxidative degradation of heme yields open-chain tetrapyrrole as a waste product in humans and other higher animals. The yellow color of the skin in jaundice victims is caused by the presence of biluubin [635-65-4] (32, R = (CH2)2COOH). 

Bilirubin [635-65-4] M 584.7, e450nm t OO in CHCI3, pKE t 3 0. An acyclic tetrapyrrole bile pigment with impurities which can be eliminated by successive Soxhiet extraction with diethyl ether and MeOH. It crystallises from CHCI3 as deep red-brown rhombs, plates or prisms, and is dried to constant weight at 80 under vacuum, [Gray et al. J Chem Soc 2264, 2276 1961.]... 

Corrole is a tetrapyrrolic macrocycle 1-Norbomyl is a bicyclo[2.2.1]hept-l-yl... 

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 ... 

Interesting tautomeric possibilities exist in the xanthobilirubic acid series (cf. reference 57) which can be illustrated by the equilibrium 62 63, More complex examples of the same type are found among the linear tetrapyrrole pigments— the bilenes, bilidienes, and bili-trienes—and have been discussed by Stevens. Relatively little evidence is available concerning the fine structure of these compounds, although the formation of complexes has been advanced as evidence for the 0X0 structure in some cases. ... 

Gray and his associates have discussed equilibria involving the side chains of tetrapyrrole bile pigments. 

Cyclization of l-bromo-19-methyl-1.19-dideoxybiladicnes-ac 11 to porphyrins 12 occurs simply by heating the tetrapyrrole in 1,2-dichlorobenzene solution or in few cases in dimethyl sulfoxide. 

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 synthesis of hexahydroporphyrins has been achieved using two principal routes. The first route makes use of cyclizations of linear tetrapyrroles which are alkylated at the /i-positions to block the corphin-porphyrinogcn tautomerization after cyclization has been performed. In the second route the metal-induced tautomerization of porphyrinogens is utilized to obtain conjugated hexahydroporphyrins. 

The starting material could be synthesized from the corresponding known dibenzyl tetrapyrrole-dicarboxylate17 by hydrogenolytic cleavage of the benzyl esters followed by decarboxylative Clezy formylation.18... 

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