Why is Porphobilinogen the Biological Substrate for the Formation of Porphyrins? Calculations on the Conformation of Acyclic Tetrapyrroles and the Acid‐Catalyzed Cyclization of Hydroxymethylpyrroles

The substitution patten of pyrrole is crucial for the ready conversion of porphobilinogen (1) into uroporphyrinogen III (6). This was indicated by model reactions with hydroxymethylpyrroles 2–5 and the results of semiempirical calculations. These calculations showed that the acyclic tetramer from 3, formulated as intermediate, has a preferred cyclic conformation as a result of 1,3-allylic strain; cyclization of this conformation should be quite facile. P=(CH2)2CO2H, A=CH2CO2H.