Oxo-bacteriopyropheophorbide-a carboxylic acid and esters thereof
A compound having the structural formula: where R is H or lower alkyl of 1 through 12 carbon atoms. In general, the compounds of the invention are 13 2 -Oxo-bacteriopyropheophorbide—a carboxylic acid and C 1 –C 12 alkyl esters thereof. A method for the preparation of the carboxylic acid compounds of the invention includes the step of reacting bacteriopyropheophorbide—a alkyl ester with lithium hydroxide tetrahydrofuran and water. A method of the invention for the preparation of the C 1 –C 12 alkyl ester compounds of the invention includes the steps of reacting bacteriopyropheophorbide—a alkyl, especially methyl, ester with lithium hydroxide in tetrahydrofuran and water to obtain 13 2 -Oxo-bacterio-pyropheophobide-a carboxylic acid followed by reacting the carboxylic acid with an acid chloride producing reagent to obtain the 13 2 -Oxo-bacterio pyropheophobide-a acid chloride (compound 5) and reacting the 13 2 -Oxo-bacterio pyropheophobide-a acid chloride with a C 1 –C 12 alcohol to obtain a 13 2 -Oxo-bacterio-pyropheophobide-a carboxylic acid C 1 –C 12 alkyl ester (compound 6). The compounds of the invention may be used as long wavelength absorbing photosensitizers for photodynamic therapy.
1. A compound of the formula:
where R is H or lower alkyl of 1 through 12 carbon atoms.
2. The compound 13 2 -Oxo-bacteriopyropheophorbide-a carboxylic acid.
3. The compound 13 2 -Oxo-bacteriopyropheophorbide-a carboxylic acid C 1 –C 12 alkyl ester.
4. The compound of claim 3 where the alkyl ester is a C 1 –C 8 alkyl ester.
5. The compound of claim 3 where the alkyl ester is a methyl, ethyl or propyl ester.
6. A method for the preparation of the compound of claim 1 where R is hydrogen by reacting bacteriopyropheophorbide-a alkyl ester with lithium hydroxide in tetrahydrofuran and water.
7. A method for the preparation of the compound of claim 1 where R is lower alky of 1–12 carbon atoms by reacting bacteriopyropheophorbide-a alkyl ester with lithium hydroxide in tetrahydrofuran and water to obtain 13 2 -Oxo-bacterio-pyropheophobide-a carboxylic acid followed by reacting the carboxylic acid with an acid chloride producing reagent to obtain the 13 2 -Oxo-bacterio pyropheophobide-a acid chloride and reacting the 13 2 -Oxo-bacterio pyropheophobide-a acid chloride with a C 1 –C 12 alcohol to obtain a 13 2 -Oxo-bacteriopyropheophobide-a carboxylic acid C 1 –C 12 alkyl ester.
8. The method of claim 7 where the acid chloride producing reagent is selected from the group consisting of thionyl chloride, phosphorous trichloride, phosphorous pentachloride and oxylyl chloride.
9. The method of claim 8 where the acid chloride producing reagent is oxylyl chloride.
10. A method for the preparation of the compound of claim 1 where R is methyl by reacting bacteriopyropheophorbide-a alkyl ester with lithium hydroxide in tetrahydrofuran and water to obtain 13 2 -Oxo-bacterio-pyropheophobide-a carboxylic acid followed by reacting the carboxylic acid with methyl azide to obtain a 13 2 -Oxo-bacterio-pyropheophobide-a carboxylic acid methyl ester.