Meso Substitution of Chlorophyll Derivatives: Direct Route for Transformation of Bacteriopheophorbides d into Bacteriopheophorbides c
In order to develop a procedure for direct methylation of methyl bacteriopheophorbides d (Bmph-d) to afford methyl bacteriopheophorbides c (Bmph-c), several reactions involving meso substitution of chlorophyll derivatives were investigated. Treatment of zinc(II) methyl mesopyropheophorbide a (7b) with bromine in chloroform accomplished oxidation, presumably via the π-cation radical, to the corresponding porphyrin, phylloerythrin methyl ester (16); meso bromination (to give 17) resulted when metal-free methyl mesopyropheophorbide a (7) was treated with bromine in chloroform. Friedel-Crafts cyanation (cyanogen bromide/aluminum chloride) of copper(II) methyl mesopyropheophorbide a (7a) gave 40-50% yields of the mesocyanochlorin 18 after demetalation, but attempts to transform the cyano group into methyl were unsuccessful. Oxidation reactions of 7 using thallium(III) trinitrate resulted in formation of the corresponding mesonitrochlorins 20. Treatment of copper(II) methyl mesopyropheophorbide a (7a) with chloromethyl methyl sulfide and titanium tetrachloride afforded the meso-methylthiomethyl derivative 19a (74-77% yields); use of the nickel(II) complex 7d likewise gave 80-84% yields of 19b. With Raney nickel, both 19a and 19b gave good yields of the required meso-methyl metallochlorins 3a and 3b, respectively, the former being readily demetalated with HC1 gas in dichloromethane to give the meso-methylchlorin 3. Thus, the Bmph-d to Bmph-c transformation was accomplished by initially protecting the vinyl group in methyl pyropheophorbide a (9) as the corresponding 2-chloroethyl group; the copper(II) complex 25a was then methylthiomethylated, treated with Raney nickel (to give 26a), and finally demetalated with HC1 gas to give 27. Compound 27 has previously been converted into Bmph-c [Et, Me] (4) by treatment with base (to give the 2-vinyl derivative) followed by hydration of the vinyl with HBr in acetic acid. © 1985, American Chemical Society. All rights reserved.
Publication Source (Journal or Book title)
Journal of the American Chemical Society
Smith, K., Goff, D., & Simpson, D. (1985). Meso Substitution of Chlorophyll Derivatives: Direct Route for Transformation of Bacteriopheophorbides d into Bacteriopheophorbides c. Journal of the American Chemical Society, 107 (17), 4946-4954. https://doi.org/10.1021/ja00303a021