Biosynthesis of porphyrins and related macrocycles. Part 52.1'2 Synthesis of 1-SH11-4Hjporphobilinogen and the (11R)enantiomer for stereochemical studies on hydroxymethylbilane synthase (porphobilinogen deaminase)

Article abstract of DOI:10.1039/a904262h

A synthetic route is devised for the synthesis of (115)-[11-²H,]porphobilinogen la and of the (1 lβ)-enantiomer Ib. Their absolute configurations and enantiomeric purity are established by degradation to a derivative of [2-2H,]glycine of known stereochemistry. Methods are then developed, based on the synthesis of chiral imidate esters, for determination of the configuration of [₂H₁]-labelled aminomethylpyrroles by converting them into [2H,]-labelled amidines followed by analysis using 'H-NMR. The labelled samples of PEG la and Ib serve as substrates for hydroxymethylbilane synthase and the products are trapped as [²H₁]-labelIed aminomethylbilanes 7c and 7d. Their configurations are determined by the NMR assay to demonstrate that as PBG 1 is enzymically converted into the aminomethylbilane 7, there is overall retention of configuration at the aminomethyl carbon. The Royal Society of Chemistry 1999.