Synthesis of analogues of porphobilinogen

Abstract

Syntheses are described of several analogues of porphobilinogen intended as substrates and/or inhibitors of porphobilinogen deaminase (hydroxymethylbilane synthase). 2-Methylporphobilinogen 12 has been synthesised from α-methylpyrrole 6, whereas a phosphonate analogue 20 of porphobilinogen, 8,9-didehydroporphobilinogen 26 and 9-fluoroporphobilinogen 38 have all been made from the 1H-pyrrolo[2,3-c]pyridine 14. The best route to 38 avoids fluoroacrylate 28 because of loss of fluorine during reduction of the double bond.