Deuteroporphyrin 11

The Vilsmeier formylation of copper deuteroporphyrin dimethyl ester (6) in which unsubstituted /3-positions are present yields a complex mixture of mono- and disubstituted formylation products which can be partially separated by chromatography on neutral alumina.106... 

In contrast to the Vilsmeier formylation the formylation with trimethyl orthoformate in trifluoroacetic acid proceeds with high selectivity so that only the /3-monoformylated deuteroporphyrin derivatives 8 are formed without any methinc substituted or diformylated products.1073 6... 

A similar rcgioselccti vity is observed in the Friedel-C rafts acylation of copper deuteroporphyrin dimethyl ester (6) which gives a mixture of two /Fmonoacylated products 9 when the reaction time and temperature are carefully controlled or diacylated products 10 on prolonged reaction time.85b-100 106 As with the four / -monoformylated deuteroporphyrin derivatives 7a. the acylated products can be separated by chromatography.100106... 

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 reactions of alkyl halides with Fe(II) deuteroporphyrin IX have been examined (Wade and Castro 1973). Three classes of reaction were observed (i) hydrogenolysis, (ii) elimination to alkenes, and (iii) coupling of alkyl free radicals. Further discussion has been given in Castro (1998). 

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. 

The NIS investigation of heme complexes includes various forms of porphyrins (deuteroporphyrin IX, mesoporphyrin IX, protoporphyrin IX, tetraphenylpor-phyrin, octaethylporphyrin, and picket fence porphyrin) and their nitrosyl (NO) and carbonyl (CO) derivatives, and they have been the subject of a review provided by Scheidt et al. [109]. 

BNCT sensitisers are designed with neutron capture in mind, but those that are porphyrin/ phthalocyanine-based may show PDT activity. An example is the disodium (or dipotassium) salt of the tetrakis-carborane ester (58) derived from 3,8-bis(l,2-dihydroxyethyl)deuteroporphyrin.298 This is water soluble and tumor selective, showing high tumor/normal brain ratios.299 Photophysical properties are similar to other water-soluble porphyrins in rat glioma cells, specific localization in mitochondria is observed.300... 

Tin(IV)-protoporphyrin (254), Ga-deuteroporphyrin (255), and Co-mesoporphyrin (256) complexes are potent inhibitors of heme oxygenase. The Sn(IV) complex significantly inhibits bilirubin production... 

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. 

Fundamentally the synthesis of the porphyrins consists in condensation (by fusion) of two suitable pyrromethines with elimination of HBr and simultaneous dehydrogenation. The formulae represent this process in the case of deuteroporphyrin ... 

Fig. 4. HPLC analyses of a deuteroporphyrin-containing, mixcoupling product. (A) Monomer-free material separated using a Sephadex LH-20 column. (B) After hydrolysis in 1M NaOH, 50J aqueous THF, showing formation of hematoporphyrin (HP) and deuteroporphyrin (DP).

Table 7.3.2 Standard (Std) solutions used for the determination of urinary porphyrin concentration. 1ST Deuteroporphyrin IX (2,4-bis-glycol)...

R1 = R2 = Et, mesoporphyrin dimethyl ester, H2MPDME R1 = R2 = H, deuteroporphyrin dimethyl ester, H2DPDME R1 = R2 = CH=CH2, protoporphyrin IX dimethyl ester, H2PPDME R1 = R2 = CH(OH)Me, hematoporphyrin dimethyl ester, H2HPDME... 

Table 5 Basicity of Substituted Deuteroporphyrin-IX Dimethyl Esters...

Early workers appeared to show that electrophilic substitution reactions could not be carried out on porphyrins, and began to question the aromaticity of porphyrins since this classical pre-requisite of aromatic character could not be accomplished. However, they had concentrated on reactions of metal-free systems, and since many electrophilic substitution reactions utilize acidic conditions (nitration, sulfonation), they were actually dealing with the non-nucleophilic porphyrin dication. But, as early as 1929, H. Fischer had realised that diacetylation of deuteroporphyrin-IX (Table 1) had to be carried out on a metal complex, such as the iron (III) derivative chelation with a metal ion which cannot be removed under the acid conditions of the subsequent reaction, effectively eliminates dication formation. A judicious choice of metal complex therefore needs to be made for any particular reaction. For example, though magnesium(II) produces an extremely reactive substrate for electrophilic substitution reactions, it is removed by contact with the mildest of acids and is, consequently, of little use for this purpose. 

---