Biosynthesis of porphyrins and related macrocycles. Part 29. Synthesis and chemistry of 2,2-disubstituted 2H-pyrroles (pyrrolenines)

Abstract

Syntheses are described of three 2H-pyrroles (pyrrolenines), (15), (28), and (64), which were designed to test the chemical feasibility of the rearrangements proposed as part of the mechanism of the enzyme cosynthetase (uroporphyrinogen III synthase). All three syntheses create the 2H-pyrrole ring by the Michael addition of a nitronate anion to an α,β-unsaturated ester and one introduces an additional substituent by novel alkylations of the dianion of a hydroxamic acid. Some of the intermediates in the syntheses showed unusual n.m.r. properties which reveal strong conformational preferences. The rearrangement of the 2H-pyrroles was studied under both thermal and acid-catalysed conditions. The results show that 2,2-disubstituted 2H-pyrroles only rearrange easily by [1,5]-sigmatropic shifts if they do not have further substituents on C-3 and C-4. 2-Pyrrolylmethyl-2H-pyrroles prefer to rearrange by a fragmentation-recombination mechanism.