N-Butyldeoxynojirimycin (NB-DNJ) is a potent reversible oral malecontraceptive agent, in mice. It has been hypothesized that NB-DNJ is impairingspermatogenesis by inhibiting ceramide-specific glucosyltransferase in thepathway for glycosylation of sphingolipids. Since NB-DNJ is a weak inhibitor ofthe enzyme, we initiated a program with the goal to discover more potentanalogues of NB-DNJ. One of the approaches that we pursued was to prepare andtest ring-enlarged analogues. Towards this goal we prepared 8-memberediminosugar analogues. Key synthetic steps towards the synthesis of the8-membered analogues included a ring-closing metathesis reaction and theSharpless asymmetric hydroxylation. The ring-closing metathesis reaction provideddifferent E:Z ratios depending on the protecting group at the secondary amine of the diene. The N-alkyl 8-membered iminosugars were tested for inhibitory activity against ceramide-specific glucosyl transferase and were found to be inactive.

Synthesis of novel eight-membered ring iminosugars as
potential male contraceptive agents

239th National Meeting (2010)

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Synthesis of novel eight-membered ring iminosugars as potential male contraceptive agents