Meso Substitution of Chlorophyll Derivatives: Direct Route for Transformation of Bacteriopheophorbides d into Bacteriopheophorbides c

Article abstract of DOI:10.1021/ja00303a021

In order to develop a procedure for direct methylation of methyl bacteriopheophorbides d (Bmph-d) to afford methyl bacteriopheophorbides c (Bmph-c), severalm 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 ?-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 40-50percent yields of the meso-cyanochlorin 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 meso-nitrochlorins 20.Treatment of copper(II) methyl mesopyropheophorbide a (7a) with chloromethyl methyl sulfide and titanium tetrachloride afforded the meso-methylthiomethyl derivative 19a (74-77percent yields); use of the nickel(II) complex 7d likewise gave 80-84percent 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 HCl 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-chloroethylgroup; the copper(II) complex 25a was then methylthiomethylated, treated with Raney nickel (to give 26a), and finally demetalated with HCl gas to give 27.Compound 27 has previously been converted into Bmph-c (4) by treatment with base (to give the 2-vinyl derivative) followed by hydration of the vinyl with HBr in acetic acid.