Synthesis of a linear α-hydroxymethyl-pentapyrrole derivative and its cyclization to uroporphyrinogens

A linear pentapyrrole bearing α-hydroxymeythyl group in the terminal was synthesized by the stepwise coupling of α-free pyrrole with azafulvenium ion 6. When it was treated with a catalytic amount of p-toluensulfonic acid under anaerobic condition, followed by aerial oxidation of the products, a statistical mixture of uroporphyrin I–IV octamethyl esters was obtained. It is proposed that this transformation proceeds through a spiro-pyrrolenine as a key intermediate.