Benzochlorins

As with other first-row transition metals, copper complexes are not expected to be satisfactory singlet oxygen photogenerators, because of the rapid deactivation of excited states in the presence of partially filled d-orbitals. The exceptional case of the copper(II) benzochlorin iminium salt ((18), M = Cu) has already been referred to (Section 9.22.5.6) this showed bioactivity, although the nickel(II) complex ((18), M = Nin) was inactive.195... 

Momenteau et al. described the preparation of amphiphilic glyco-conjugated meso-monoarylbenzochlorins from meso-monoarylporphyrins.74 The reaction of metal free benzochlorin 94 with 1-bromoethoxy-per-acetyl-maltose, in DMF and in the presence of potassium carbonate, gives compound 95b in 95% yield (Scheme 12). After deacetylation of 95b maltosylchlorin 95a was obtained quantitatively. 

Other photosensitisers in clinical or pre-clinical trials include zinc phthalocya-nine, aluminium sulphonated phthalocyanines, benzoporphyrins, benzochlorins and purpurin-lS-iV-alkylamides, all of which absorb strongly in the 675-700 nm region. An alternative approach to the photosensitisation in PDT involves the use of 5-aminolaevulinic acid (ALA). This compound itself is not a sensitiser but in human cells it is the key metabolic precursor in the biosynthesis of protoporphyrin IX, which can act as a photosensitiser. Normally the biosynthetic process would continue beyond protoporphyrin IX to the iron containing haem. However, by adding extra ALA and iron chelators, the ferrochelatase action is inhibited and the normal feedback mechanism by-passed resulting in a build up of protoporphyrin IX in the cell. The mechanism is illustrated in Figure 4.24. ... 

Garbo GM. Purpurins and benzochlorins as sensitizers for photodynamic therapy. J Photochem Photobiol B Biol 1996 34 109-16. 

Momenteau et al. described the preparation of amphiphihc glycoconju-gated meso-monoarylbenzochlorins from meso-monoarylporphyrins [153]. The metalloporphyrin 218 when treated with 3-(dimethylamino)acrolein under Vilsmeier conditions led to two isomeric compounds 219 and 220 in 85% total yield and 2 3 ratio treatment of isomer 219 with TEA afforded the benzochlorin 221 in 58% yield and only one of the two possible benzochlorin isomers was obtained (Scheme 42). The dealkylation of the methoxy group... 

The reactions between benzochlorin 244 and acetylated galactosamine, glucosamine and lactosamine were performed in dry dichloromethane in the presence of triethylamine and the coupling reagent BOP. The corresponding... 

The same research group has also prepared benzochlorin-C-galactose conjugates to investigate their PDT efficacy. 

TEA gave rise to the free-base benzochlorin-galactose conjugate 249a in 97% yield (Scheme 48) [48]. 

Benzochlorin 50 consists of a benzene ring fused to the tetrapyrrolic structure and was first reported by Arnold et from octaethylporphyrin H2(OEP) in several steps such as, formylation, Wittig reaction, reduction and oxidation. Morgan et al. followed this approach and benzochlorins 54 and 55, as major and minor products, respectively, were obtained (Scheme 15). 

A very similar type of benzochlorin 50 was also synthesized by Smith s group as a result of the cyclization of the product obtained after Vilsmeier formylation reaction of Ni or Cu(OEP) using dimethylaminoacrolein and phosphorous oxychloride.The utility of this class of compounds as photosensitizers for PDT was first shown by Morgan et Jn a mouse tumor model. With a few... 

One of the major problems associated with benzochlorin preparation is the difficulty in demetalation at the final step of the synthesis. Gunter et converted a series of Ni(II) 5,15-diphenylporphyrins 56 into the corresponding benzochlorins, which upon acid treatment produced the corresponding free-base analogue 57 in excellent yield. 

It has been shown by Fischer and Clezy et al. that the porphyrin containing tetrapropionic ester functionalities 72 can be converted into rhodin 73 which, upon treament with fuming sulfuric acid in the presence of air, can beconverted into benzochlorin 74 62 jn modest yield (Scheme 19). 

Scheme 16. Free-base benzochlorins from 5,15-diphenyl-TPP.

The work of Barloy et has demonstrated that in the H2(TPP) series, the formyl group present at the peripheral position in 79 in acidic conditions undergoes an intramolecular cyclization to produce benzochlorin-type compounds 80 (Scheme 22). 

Scheme 23. Some novel benzochlorins from 5,15-diphenylporphyrin.

Chlorins and Bacteriochlorins by Diels Alder Reaction Benzochlorins and Benzobacteriochlorins Purpurins (Tin Etiopurpurin Dichloride)... 

Benzochlorin consists of a benzene ring fused between the meso- and the adjacent 3-position of the pyrrole ring. In a sequence of reactions, this class of compounds was first reported by Arnold et al. from... 

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