Biosynthesis of porphyrins and related macrocycles. Part I. Synthesis of 14C-labelled pyrromethanes

Abstract

The biosynthetic problem posed by the macrocycle of the natural porphyrins, chlorins, and corrins is outlined together with the approaches being used for its solution. Routes are developed as follows for rational synthesis of the labelled (aminomethyl)pyrromethanes (6) and (7), which are of importance for incorporation studies on haem, protoporphyrin-IX, and vitamin B₁₂. An improved sequence affords porphobilinogen lactam methyl ester (16) labelled in the propionic ester residue. The 5-(chloromethyl)pyrrole (24) is synthesised carrying ¹⁴C-labels at the C-4 methylene and C-5 methylene groups. A similar synthesis yields the labelled isomeric (chloromethyl)pyrrole (52). These three building blocks are used for synthesis of the pyrromethane lactams (27) and (55) of proven homogeneity labelled specifically with carbon-14 in the side-chains and at the bridge methylene group. Hydrolysis of the lactams affords the labelled (aminomethyl)pyrromethanes (6) and (7).