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DOI: 10.1039/A904262H (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1999, 2677-2689

Biosynthesis of porphyrins and related macrocycles. Part 52. Synthesis of (11-S[hair space])-[11-2H1]porphobilinogen and the (11R)-enantiomer for stereochemical studies on hydroxymethylbilane synthase (porphobilinogen deaminase)

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Werner L. Neidhart, Paul C. Anderson, Graham J. Hart and Alan R. Battersby

Abstract

A synthetic route is devised for the synthesis of (11S[hair space])-[11-2H1]porphobilinogen 1a and of the (11R)-enantiomer 1b. Their absolute configurations and enantiomeric purity are established by degradation to a derivative of [2-2H1]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 [2H1]-labelled amidines followed by analysis using 1H-NMR. The labelled samples of PBG 1a and 1b serve as substrates for hydroxymethylbilane synthase and the products are trapped as [2H1]-labelled 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.

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