Synthesis of N-(formylmethyl)protoporphyrin and N-(2-hydroxyethyl)protoporphyrin IX dimethyl esters

Abstract

N-(Formy lmethyl)protoporphyrin IX dimethyl ester zinc chloride and the corresponding dimethyl acetal were synthesized by the electrochemical reduction of N,Co-(formylmethylene) protoporphyrin IX dimethyl ester cobalt(III) chloride. This species, in which the cobalt and a porphyrin nitrogen are bridged by a single carbon atom, was prepared from the reaction of protoporphyrin IX dimethyl ester cobalt(II) with diazoacetaldehyde. IV-(2-Hydroxyethyl)protoporphyrin IX dimethyl ester zinc chloride was obtained by the reduction of the corresponding N-formylmethyl complex with LiAlH(0-t-C4H9)3. The free bases of all of the zinc complexes were obtained by acid-catalyzed demetalation.It has recently been reported that the prosthetic heme of cytochrome P-450 monooxygenases is converted into abnormal green porphyrins during the metabolism of 1,4-dihydropyridine derivatives,1-4 terminal olefins,5 terminal acetylenes,6,7 1-aminotriazole,8 and cyclopropyl amines.9,10 N-Methylprotoporphyrin IX dimethyl ester with the N-methyl group specifically on ring A was characterized for the hepatically derived porphyrin biologically modified by 3,5-dicarbethoxy-l,4-dihydrocollidine on the basis of chemical synthesis and HPLC separation of four possible isomers of (N-methyl)-PPIXDME.2'1