Biosynthesis of porphyrins and related macrocycles. Part 52. Synthesis of (11-S)-[11-H-2(1)]porphobilinogen and the (11R)-enantiomer for stereochemical studies on hydroxymethylbilane synthase (porphobilinogen deaminase)

A synthetic route is devised for the synthesis of (11S)-[11-H-2(1)]porphobi linogen 1a and of the (11R)-enantiomer 1b. Their absolute configurations an d enantiomeric purity are established by degradation to a derivative of [2- H-2(1)]glycine of known stereochemistry. Methods are then developed, based on the synthesis of chiral imidate esters, for determination of the configu ration of [H-2(1)]-labelled aminomethylpyrroles by converting them into [H- 2(1)]-labelled amidines followed by analysis using H-1-NMR. The labelled sa mples of PBG 1a and 1b serve as substrates for hydroxymethylbilane synthase and the products are trapped as [H-2(1)]-labelled aminomethylbilanes 7c an d 7d. Their configurations are determined by the NMR assay to demonstrate t hat as PBG 1 is enzymically converted into the aminomethylbilane 7, there i s overall retention of configuration at the aminomethyl carbon.