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

• Published in: Tetrahedron: asymmetry 2011-11, Vol.22 (20), p.1855-1860
• Main Authors: Venkataiah, Mallam, Reddipalli, Gowrisankar, Jasti, Lakshmi Swarnalatha, Fadnavis, Nitin W.
• Format: Article
• Language: English
• ISSN: 0957-4166; 1362-511X
• 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 OsO 4 in 29% overall yield over 11 high yielding steps. Enzyme inhibition studies showed that 1,4-dideoxyallonojirimycin is a better β-glucosidase inhibitor (IC 50 32.4 μM toward β-glucosidase from almonds) and a better β-galactosidase inhibitor (IC 50 5.9 mM for β-galactosidase from Aspergillus oryzae) than 1,4-dideoxymannojirimycin (IC 50 2.86 mM and 12.5 mM for β-glucosidase and β-galactosidase, respectively).