Chemical synthesis of porphobilinogen and studies of its biosynthesis

A review with many refs. and some new data. Porphobilinogen is the second dedicated intermediate in the biosynthesis of tetrapyrroles. The substitution pattern attributes a high reactivity to porphobilinogen. The published synthesis of the unusual pyrrole is reviewed and analyzed according to the synthetic strategies used. In order to compare the chem. 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 understanding 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 the study. To elucidate the enzyme catalyzed reaction the known inhibitors of PBGS are comprehensively reviewed and the authors expts. with specially designed inhibitors are reported. As a consequence of the studies and following a proposal from Shemin, a chem. attractive mechanism is discussed. [on SciFinder(R)]