Chemo-enzymatic synthesis of the azasugars 1,4-dideoxyallonojirimycin and 1,4-dideoxymannojirimycin

Article abstract of DOI:10.1016/j.tetasy.2011.10.015

The enzymatic resolution of the N-phenylacetyl derivative of racemic homoserine lactone with penicillin G acylase immobilized on Eupergit C gave (R)-(+)-α-amino-γ-butyrolactone and (S)-(-)-α-N- phenylacetamido-γ-butyrolactone in high enantiomeric purity (ee >99%) and 46-47% yields for each enantiomer. The enantiomers were converted into azasugars 1,4-dideoxyallonojirimycin and 1,4-dideoxymannojirimycin using Wittig olefination, catalytic ring-closing metathesis (RCM), and stereoselective dihydroxylation with OsO₄ in 29% overall yield over 11 high yielding steps. Enzyme inhibition studies showed that 1,4-dideoxyallonojirimycin is a better β-glucosidase inhibitor (IC₅₀ 32.4 μM toward β-glucosidase from almonds) and a better β-galactosidase inhibitor (IC₅₀ 5.9 mM for β-galactosidase from Aspergillus oryzae) than 1,4-dideoxymannojirimycin (IC₅₀ 2.86 mM and 12.5 mM for β-glucosidase and β-galactosidase, respectively).