NEW SYNTHESES OF DEUTERATED PROTOPORPHYRIN-IX DERIVATIVES FOR HEME PROTEIN NMR-STUDIES

An efficient total synthesis of 1,5-di(trideuteromethyl)protoporphyrin-IX (3) dimethyl ester from monopyrrole precursors is described, the synthesis proceeding through crystalline tripyrrene and a,c-biladiene salt intermediates. The 2- and 4-vinyl groups in (3) are formed from the corresponding (2-chloroethyl) substituents by way of base-promoted dehydrochlorination. In protio solvents, this synthetic step is shown to exchange out preferentially deuterons in the 1-methyl group, and this observation is exploited in an efficient synthesis of the 1,3-di(trideuteromethyl)protoporphyrin-IX (22) dimethyl ester from 2,4-diacetyldeuteroporphyrin-IX (20) dimethyl ester (which is in turn accessible from commercially available protoporphyrin-IX (5)). Thus, basic exchange in deuterated solvent of (20) gives the deuterated analog, which after reduction and dehydration gives the 1,3-di(trideuteromethyl)protoporphyrin-IX analog (22), in which the vinyl H2 and propionic CH2·CO functions have also become deuterated. © 1979.