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.
Publication Source (Journal or Book title)
Smith, K., Eivazi, F., Langry, K., de Almeida, J., & Kenner, G. (1979). New syntheses of deuterated protoporphyrin-IX derivatives for heme protein nmr studies. Bioorganic Chemistry, 8 (4), 485-495. https://doi.org/10.1016/0045-2068(79)90050-6