Porphyrinogen

Porphyrin, 5,10,15,20-tetraphenyl-, 4, 386 Porphyrin, vinyl-synthesis, 4, 278, 279 Porphyrin coenzymes in biochemical pathways, 1, 258-260 Porphyrinogen, mcso-tetraaryl-synthesis, 4, 230 Porphyrinogens, 4, 378, 394 pyrazoles, 5, 228 synthesis, 4, 231 Porphyrins, 4, 377-442 acetylation, 4, 395 aromatic ring current, 4, 385 basicity, 4, 400 biosynthesis, reviews, 1, 99... 

Porphyrinogen-porphyrin relationship the discovery of artificial porphyrins 96CC1257. 

Cyclization of 5, for entropic reasons via conformer 5, yields a porphyrinogen 6. Porphyrinogens 6 are extremely sensitive to oxidation so that even aereal oxidation gives the desired porphyrin 7 (contaminated sometimes by the cyclized dihydroporphyrin, i.e. chlorin 8). 

The enzymatic conversion of a-(aminomethyl)pyrroles is also used by nature to produce porphyrinogens like uroporphyrinogen III (see introduction, compound 8), which is the key building block in the biosynthesis of all known porphinoid natural products. This biomimetic method is a powerful tool for the synthesis of different porphyrins, e.g. for the preparation of JV,Af, V ,Ar"-tetramethylporphyrin-2,3,7,8,12,13,17,18-octaacetic acid dibromide 12.36... 

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. 

The tautomerization is induced by cobalt(II) which forms the thermodynamically more stable metalatcd hydroporphyrins from which the cobalt can be removed using trifluoroacctic acid under kinetic control. Experiments with porphyrinogen and hexahydroporphyrin show that the porphyrinogen-hexahydroporphyrin equilibrium can be shifted by complexation of porphyrinogen with metal ions to the more stable metal hexahydroporphyrins and that metal-free hexahydroporphyrins tautomerize back to the more stable metal-free porphyrinogens.29... 

During the systematic investigation of the tautomerization of octacthyl porphyrinogen 2110 it was observed that hexahydroporphyrins 22 could be oxidized in the presence of air to bac-teriochlorins 23 and isobactcriochlorins 24 (both tetrahydroporphyrins) on complexation with nickel(II) acetate. 

Transformations of isobacteriochlorins are rare. The hydrogenation of isobacteriochlorins, e.g. 1,llb-24 ieacjs t0 dihydroisobacteriochlorins, e.g. 2. which are on the same oxidation level as hexahydroporphyrins or porphyrinogens. The dihydrogenated forms of sirohydrochlorin and 20-methylsirohydrochlorin (which are also called precorrin 2 and precorrin 3, respectively) have been identified as important intermediates in the biosynthesis of vitamin B, 2.5... 

Systematic investigations have deary demonstrated that in the presence of metal ions the conjugated hexahydroporphyrin forms are thermodynamically favored by complexation whereas in the absence of metal ions the porphyrinogen form with isolated aromatic pyrrole rings is the thermodynamically stable tautomer. 

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. 

From Porphyrinogens and Other Hexahydroporphyrins by Tautomerization and Alkylation... 

The tautomerization of porphyrinogens to pyrrocorphins has been reported in detail in connection with the synthesis of chlorins (sec Section 1.2.1.3.), baeteriochlorins (see Section 1.3.1.) and isobacteriochlorins (see Section 1.4.1.3.). Therefore, only the porphyrinogen-pyrrocorphin tautomerization of uroporphyrinogen I octacarbonitrile 8- 96 will be described as it is of importance regarding the biosynthesis and a possible prebiotic formation of corrins.la,b-2 A major problem concerned with using this approach synthetically is the number of possible diastereomeric products (4 in a 1 1 1 1 ratio) obtained in the reaction and also the formation of isobacteriochlorin diastereomers 10. 

Acid-induced cyclization of the appropriate (hydroxypropenyl)pyrroles 30, which can be easily derived from a-unsubstituted pyrroles by vinylogous Vilsmeier reaction followed by reduction of the formyl function, yields the corresponding expanded porphyrinogens 31. The... 

In contrast, porphyrinogens 16 (Fig. 5) possess only 16 Ti-electrons and as a consequence the delocalization over the whole macrocycle is absent. The conformations of porphyrinogens are not planar any more and can approximate to the conformations known for calix[4]arenes (vide supra). Compounds 16 (Fig. 5) may, therefore, be considered as heteroatomic calixarene derivatives, of which some have additional heteroatoms in the bridging positions [15, 28-30]. 

As in the case of the tetrameric macrocycles discussed above, compounds 17 and 18 can be considered as porphyrinogen analogues or as heteroatom-bridged heteroaromatic calix[4]arene derivatives. The two different conformations observed for 17 and 18 have analogues in compounds 16 (Fig, 5) [15, 28-30],... 

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