Total Syntheses of Derivatives of Protoporphyrin IX Regioselectively Labeled with Carbon-13 in the Methyls

Total syntheses, from monopyrroles via tripyrrenes and a,c-biladienes, of the four isomers 2–5 of protoporphyrin IX dimethyl ester in which the 1-, 3-, 5-, and 8-methyl groups are individually and regioselectively enriched with carbon-13 are described. The source of labeled carbon was 90% carbon-13-enriched paraformaldehyde, and methyls were inserted at the monopyrrole stage by reductive C-alkylation. The carbon-13-labeled porphyrins, as the corresponding hemes, are of interest as probes in carbon-13 NMR spectroscopic studies of reconstituted heme proteins.