Pyrrole chemistry. XXVII. 2,3,4-Trisubstituted pyrroles and a second synthesis of porphobilinogen from pyrrole

Abstract

Changes in some of the key intermediates and procedures used in our earlier total synthesis of porphobilinogen from pyrrole that improve the yield to 11% are reported. Ethyl pyrrole-3-acetate was formylated by the Vilsmeier–Haack method and then iodinated. The desired 2,3,4-substituted pyrrole isomer was isolated in moderate yield and, after conversion of iodide to acrylate and aldehyde to aldoxime, reduction and work-up afforded porphobilinogen lactam ethyl ester. Hydrolysis of the latter gave porphobilinogen in ten steps from pyrrole.