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J Org Chem. 1998 Feb 6;63(3):602-607.

Regioselective Porphyrin Bridge Cleavage Controlled by Electronic Effects. Coupled Oxidation of 3-Demethyl-3-(trifluoromethyl)mesohemin IX and Identification of Its Four Biliverdin Derivatives.

Author information

1
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Sakyo-ku, Kyoto-606, Japan, Department of Materials Engineering, Nagaoka College of Technology, Nishikatakai, 888, Nagaoka, 940, Japan, and Fukui National College of Technology, Geshi, Sabae, Fukui 916, Japan.

Abstract

This report describes the nonenzymatic oxidative cleavage of the title porphyrin (2) performed with oxygen and ascorbic acid in aqueous pyridine at 37 degrees C (coupled oxidation), via hydrolysis of the corresponding verdoheme intermediates, followed by esterification of the resulting free acid mesobiliverdin analogues to their dimethyl esters 4 (alpha isomer), 5 (beta isomer), 6 (gamma isomer), and 7 (delta isomer). The four biliverdin derivatives were purified by HPLC, and their structures were confirmed by FAB MS and also by UV-vis and (1)H NMR spectroscopies. The purity of each compound was checked by (19)F NMR, and the four regioisomers were assigned through their 2D-NMR ROESY spectra and confirmed by UV-vis spectroscopy. The ratio of regioisomers was determined by (19)F NMR spectroscopy before any purification of single compounds was attempted: alpha:beta:gamma:delta 11:6:26:57 (%). This unusually high regioselectivity was attributed to the electron-withdrawing effect of the CF(3) group on the electronic structure of porphyrin as shown considering the ab initio calculations of an iron(II) beta-substituted (trifluoromethyl)porphyrin used as a model compound. In porphyrin 2, the oxidation clearly takes place at the electron richest meso positions, the order of reactivity strictly following that of electron density, pointing out that the regiospecificity of the bridge cleavage can be effectively controlled by the electronic effects of some strategic substituents in the chromophore. The relevance of all these results in the study of the mechanism of the reactions involved in the natural catabolism of heme, catalyzed by heme oxygenase, is discussed. The advantages of 2 derived from this work, which make it a suitable model compound for the enzymatic reaction, are also discussed.

PMID:
11672050
DOI:
10.1021/jo9714728

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