Chemical Synthesis of Porphobilinogen and Studies of its Biosynthesis

Porphobilinogen is the second dedicated intermediate in the biosynthesis oftetrapyrroles. The substitution pattern attributes a high reactivity to porphobilinogen (= PBG <b>9</b>). The published synthesis of this unusual pyrrole is reviewed and analyzed according to the synthetic strategies used. In order to compare the chemical synthesis with the biosynthetic process, the knowledge about the enzyme porphobilinogen synthase (= PBGS) is reviewed. Special importance is given to observations, which may be significant to understand the mechanism of the enzyme catalyzed process. Efforts, which have been undertaken to imitate the enzyme catalyzed reaction are described. Two novel pyrrole syntheses have been developed in this study. To elucidate the enzyme catalyzed reaction the known inhibitors of PBGS are comprehensively reviewed and our experiments with specially designed inhibitors are reported. As a consequence of our studies and following a proposal from <i>Shemin</i>, a chemically attractive mechanism is discussed.