Pyrroles and related compounds—XXXVI : Transformations of protoporphyrin-IX into harderoporphyrin, pemptoporphyrin, chlorocruoroporphyrin and their isomers

Abstract

Treatment of protoporphyrin-IX dimethyl ester ( 8b) with 2 equiv of thallium(III) nitrate in methanol followed by chromatography affords good yields of a mixture of mono-acetal-mono-vinyl isomers ( 11b and 12b) which can be converted into the corresponding (2-hydroxyethyl)-vinyldeuteroporphyrins ( 13b and 14b) by hydrolysis and reduction with sodium borohydride. After separation by preparative TLC these compounds are transformed into isoharderoporphyrin trimethyl ester ( 3b) and harderoporphyrin trimethyl ester ( 2b) by treatment with CBr 4/Ph 3P (to afford the 2-bromoethyl derivatives), then sodium cyanide in 1-methylpyrrolidone (giving the 2-cyanoethyl compounds), followed by methanolysis. Formal syntheses of pemptoporphyrin dimethyl ester ( 4b) and its isomer ( 5b) are achieved by devinylation (resorcinol melt) of the haemins from the pure (2-hydroxyethyl)-vinyl isomers ( 14b and 13b) respectively, followed by demetallation. Controlled oxidation of protoporphydrin-IX dimethyl ester ( 8b) with osmium tetroxide gives starting material, mono-glycol-mono-vinyl isomers ( 23b and 24b), and bis-glycol ( 25b); this mixture can be separated by column chromatography. Further separation of the mono-glycols through preparative TLC followed by treatment with sodium periodate gives pure samples of chlorocruoroporphyrin dimethyl ester ( 6b) and its isomer ( 7b). In the TLC separations of unsymmetrically 2,4-substituted deuteroporphyrins studied, the 2-vinyl substituted isomers proved always to be the more polar (less mobile) componnets of the mixtures of isomers.