Isobacteriochlorins

Isay reaction, 2, 79-80 3, 259 Ismelin 7, 656 Isoalloxazine oxidation states, 1, 252 Isoaminopterin synthesis, 3, 327 Isoarsindolines, 1, 543-544 Isoarsinoline, tetrahydro-synthesis, 1, 552-553 stability, 1, 552 Isoascorbic acid structure, 4, 552 ( )-IsoavenacioIide synthesis, 1, 416 Isoazapenem synthesis, 1, 465 Isobacteriochlorin synthesis, 4, 419 Isobacteriochlorin, dimethyl-biosynthesis, 1, 105 Isobacteriochlorin, methyl-biosynthesis, 1, 105 Isobacteriochlorin, trimethyl-biosynthesis, 1, 105 Isobarbituric acid Mannich reaction, 3, 71 synthesis, 3, 133... 

Tire macrocyclic core of porphyrin systems 71 is highly conjugated and a number of effective resonance forms can be written. Tliere are nominally 22 TT-electrons but only 18 of these can be included in any one conjugative path (for a modern discussion on this topic, see references 98AGE177 and 99CEJ267). Chlorins (73, dihydroporphyrins), bacteriochlorins (74, tetra-hydroporphyrins), and isobacteriochlorins (75, tetrahydroporphyrins) also have full 18-7r delocalization available, though the number of possible resonance forms is reduced. 

Synthesis of chlorins, bacteriochlorins, isobacteriochlorins, and higher reduced porphyrins 98PHC1. 

In a study of the photoreduction of zinc(II) or magnesium chlorophyll derivatives 8 with ascorbic acid in the presence of l,4-diazabicyclo[2.2.2]octane (DABC-O), a 2,3-m-hydrogenated isobacteriochlorin 9 is formed which subsequently rearranges to a 3-ethylidenc derivative... 

Direct Vilsmeier reaction can also be applied to chlorins as in the porphyrin scries32k (see Section 1.1.2.3.). An interesting extension to this approach is the vinylogous Vilsmeier reaction with / -(dimethylamino)acrylaldehyde.24 The products, e.g. 19, can be further used for instance in the transformation of nickel(II) octaethylchlorin 18 into isobacteriochlorins. 

In contrast, with the corresponding zinc complexes isobacteriochlorins are formed. 5,10,15,20-Tetraphcnylbactcriochlorin (1, R = H) Typical Procedure 3 ... 

In the case of the osmium(VIII) oxide oxidation of 5,10,15,20-tetraphenylchlorin,3b the metal-free macrocycle gives the bacteriochlorin 6, whereas the corresponding zinc derivative leads to an isobacteriochlorin. 

Isobacteriochlorins with two adjacent saturated pyrrole rings are the constitutional isomers of bacteriochlorins, in which two neighboring rings are partially reduced. 

Whereas in porphyrins, chlorins and bacteriochlorins the 1871-aromatic perimeter includes two nitrogens excluding their lone pairs, the.1871 perimeter of the isobacteriochlorin includes three nitrogens, one with its electron lone pair as part of the aromatic perimeter. The electron pair of the /J,/J -C —C double bond of ring D of isobacteriochlorin is not involved in the cyclic conjugation path. 

In 1973, the first naturally occurring isobacteriochlorin, iron-containing siroheme, was isolated1 from a sulfite reductase of Escherichia coli. Later it was also discovered in sulfite and nitrite reductases of numerous bacteria and plants.2 Iron-free sirohydrochlorins (also called factor II) were discovered in vitamin B12 producing bacteria.3-4 Together with factor III. a sirohydrochlorin methylated in the 20-position, the reduced forms of factor II and factor III were identified as biosynthetic intermediates in the biosynthesis of vitamin B12.5... 

Heme d,6 another isobacteriochlorin, occurs as one of two cofactors in the reductase cytochrome cdj which mediates the nitrite reduction to nitrogen monoxide (NO) and from there to dinitrogen oxide (N20) in denitrifying bacteria.7... 

The important biological role of the isobacteriochlorins has decisively influenced the development of synthetic approaches leading to the isobacteriochlorin class of compounds. All of the naturally occurring isobacteriochlorins contain geminally dialkylated structural parts in the saturated pyrrole rings, which require special approaches for their synthesis. Until the discovery of siroheme and sirohydrochlorin, this structural element could only be found in vitamin B,2. Using the synthetic potential, which was invented during numerous syntheses of... 

Another approachl2a e makes use of bilenimincs which can be photochemically cyclized to isobacteriochlorins. A plausible mechanism for this ring-closure process involves the formation of an enamine tautomer from the imine at the 1-position, which is then cyclized in a photochemical 1 STc-n-isomcrization process followed by elimination of the leaving group at the 19-... 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

As for chlorins and bacteriochlorins, reactions at the chromophore periphery of porphyrins can be used to prepare isobacteriochlorins. The lack of regioselectivity in these reactions necessitates the use of highly symmetric porphyrins as starting materials. In some cases, intramolecular reactions have been used to solve the problems of regioselectivity. 

Isobacteriochlorins, since they are tetrahydroporphyrins, can be obtained by tetrahydrogena-tion of porphyrins and dihydrogenation of chlorins. However, alkali-metal reduction of porphyrins and metalloporphyrins always gives a mixture of chlorins, bacteriochlorins or isobacteriochlorins.14 The method of choice for the preparation of pure isobacteriochlorins, e.g. 2, is the diimide reduction of zinc(II) chlorins, e.g. l.15a,b... 

Nickel(II) chlorophyll derivatives undergo catalytic hydrogenation with Raney nickel as catalyst to yield stereoisomeric isobacteriochlorins in which ring A of the chlorophyll derivatives is reduced.16... 

Similiar problems of regioselectivity as in reduction reactions are encountered in oxidation reactions of porphyrins and chlorins. The oxidation of chlorins to isobacteriochlorins can be directed by insertion of zinc(II) or nickel(II) into the macrocycle. Again here, the metal-free chlorins give the bacteriochlorins whereas the metal chlorins, e.g. 1, give isobacteriochlorins, e.g. 3.15a,b I 7... 

The oxidation of octaethylporphyrin 418 with hydrogen peroxide in sulfuric acid leads under pinacol rearrangement to a mixture of hydroporphyrinones, among them the expected three constitutionally isomeric isobacteriochlorins. 

In the above route, zinc(II) can be replaced by other metal ions such as copper(II) and nickel(II). The pinacol approach to isobacteriochlorins has also been successfully applied to the synthesis of heme dj. 20a b... 

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. 

Single isobacteriochlorin stereoisomers even in enantiomcrically pure form can be obtained230 when the Claisen rearrangement is performed with the pure hematoporphyrin stereoisomers23d which can be prepared by stereogenic enantioselective reduction from diacetyl deuteroporphyrin dimethyl ester. 

The cw-isobacteriochlorin 16A formed by the Claisen rearrangement has been utilized for the further transformation into porphyrin dp2311 0 the metal-free ligand of heme dr... 

A similar rearrangement of a methyl group occurs with palladium(II) octamethylcorphin 7 which on heating is transformed into palladium(II) isobacteriochlorin 8.27... 

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... 

Oxidation reactions were used in the synthesis of porphyrin d, the metal-free ligand system of naturally occurring heme d,. In a total synthesis of porphyrin d,12d oxo functions were introduced into isobacteriochlorin 3 by selenium dioxide oxidation to yield 4. The selenium dioxide selectively attacks the 3- and 8-positions of the partially reduced pyrrole rings of the chromophore. In another synthesis23a c of porphyrin d, an isobacteriochlorin 5, derived by... 

A/eso-carboxylated isobacteriochlorins, e.g. 7, can be decarboxylated after ester hydrolysis to me.w-unsubstituted isobacteriochlorins, c.g. 8.lla... 

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. 

Experiments have been carried out to mimic the reactions of model systems for coenzyme F430 that is involved in the terminal step in the biosynthesis of methane, and that is able to dechlorinate CCI4 successively to CHCI3 and CH2CI2 (Krone et al. 1989). Nickel(I) isobacteriochlorin anion was generated electrolytically and used to examine the reactions with alkyl halides in dimethylformamide (Helvenston and Castro 1992). The three classes of reaction were the same as those observed with Fe(II) deuteroporphyrin IX that have already been noted. 

Murphy Ml, LM Siegel, H Kamin (1973) Reduced nicotinamide adenine dinucleotide phosphate-sulfite reductase of enterobacteria. II. Identification of a new class of heme prosthetic group an iron-tetrahydroporphyrin (isobacteriochlorin type) with eight carboxylic acid groups. J Biol Chem 248 2801-3814. 

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