Pyropheophorbide-a methyl ester

Thirty-nine chlorophyll transformation products were separated on a C g colunw (. = 400nm) using a 40-min gradient from 90/10 methanol/water to 90/5/5 acetone/methanol/wato- [457]. Positive identification of methylated compounds within fiactions was made by thermospray MS. Pheophoibide a methyl ester, zeaxanthin, pyropheophorbide a methyl ester, isorenieratene, pheophytin a and b and pyiopheoph5 in a and b were confirmed. 

Matroule, J.Y., Bonizzi, G., Morhere, R, PaiUous, N., Santus, R., Bours, V., and Piette, J., Pyropheophorbide-a methyl ester-mediated photosensitization activates transcription factor NFkB through the interleukin-1 receptor-dependent signaling pathway,/. Biol Chem., 270,2899,1999. Legrand-Poels, S., Schoonbroodts, S., Matroule, J.Y., and Piette, J., NF-kB an important transcription factor in photobiology, /. Photochem. Photohiol B, 45,1,1998. 

In order to compare the photophysical and biological properties of all the pyropheophorbide sugar derivatives the methyl ester derivatives 264 and 265 were also prepared by treatment with the corresponding acids with 3% sulfuric acid in methanol. The initial results obtained with these amphiphihc conjugates 262-265 showed a tendency to aggregate in aqueous and aque-ous/ethanolic solutions [169]. 

The formation of 17-alkylamide analogues of purpurin imide from the corresponding methyl ester affords a simple approach for the preparation of photosensitizers with additional lipophilic characteristic for optimizing the PDT efficacy of the parent molecule. Such modification of the pyropheophorbide analogues has induced significant... 

So far, chlorin-type photosensitizers derived from various porphyrins and from pyropheophorbide a or purpurin-18 methyl ester have been discussed. These sensitizers have a strong absorption near 700 nm, which almost doubles the tissue-penetration distance of the incident light compared with Photofrin (630 nm). However, an ideal sensitizer should absorb light at or near 800 nm, not only because of its deeper tissue penetration, but also due to the availability of cheaper diode lasers for sensitizer excitation. 

Chlorins 10 (Figure 10.2) were prepared using a similar route, from methyl pyropheophorbide-a (a chlorophyll-a derivative) by functionalization of the vinyl group using various alcohols ROH (R = methyl, propyl, pentyl, heptyl, nonyl), followed by cleavage of the ester group, activation with oxalyl chloride, and reaction with the tetramethylammonium salt of Chlorins 10... 

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