Synthesis of (R)-2-methyl-4-deoxy and (R)-2-methyl-4,5-dideoxy analogues of 6-phosphogluconate as potential inhibitors of 6-phosphogluconate dehydrogenase

Christophe Dardonville, Ian H. Gilbert

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    9 Citations (Scopus)

    Abstract

    The synthesis of (2R)-2-methyl-4,5-dideoxy and (2R)-2-methyl-4-deoxy analogues of 6-phosphogluconate is described. The synthetic strategy relies on the Evans aldol reaction for the installation of the chiral centres in the 2- and 3-positions. The selective phosphorylation at the primary alcohol function of (2R,3S)-3,6-dihydroxy-2-methylhexanoic acid benzyl ester (5) and (2R,3S,5S)-3,5,6-trihydroxy-2-methylhexanoic acid benzyl ester (20) was achieved with dibenzyl phosphochloridate and dibenzyl phosphoiodinate respectively, working at low temperature. (2R,3S)-3-Hydroxy-2-methyl-6-phosphonoxyhexanoic acid (9) was obtained in 25% overall yield from 4-benzyloxybutanol and (2R,3S,5S)-3,5-dihydroxy-2-methyl-6-phosphonoxyhexanoic acid (28) in 10% overall yield from L-malic acid.

    Original languageEnglish
    Pages (from-to)552-559
    Number of pages8
    JournalOrganic and Biomolecular Chemistry
    Volume1
    Issue number3
    DOIs
    Publication statusPublished - 2003

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