Synthesis of isofagomine and some new azasugars as glycosidase inhibitors from d-mannitol derived nitroolefins

The synthesis of isofagomine, epi-isofagomine and isofagomine analogues along with some new azasugars from two different vinyl nitro compounds, that were derived from d-mannitol, has been carried out. Two different synthetic strategies were followed for each of the vinyl-nitro precursors. Many of the azasugars synthesized showed inhibition in the micromolar range when tested against various glycosidase enzymes, opening up the possibility of modifying structural features for better and selective inhibition.

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(3aR,7S,7aR)-Benzyl 7-allyl-2,2-dimethyltetrahydro-[1,3]dioxolo-[4,5-c]pyridine-5(6H)-carboxylateC19H25NO4[α]D25=-30.0 (c 0.9, CH2Cl2)Source of chirality: d-mannitol, allyl Grignard reactionAbsolute configuration: (3aR,7S,7aR)

(3aR,7S,7aR)-5-Butyl-2,2-dimethyl-7-propylhexahydro-[1,3]dioxo-lo[4,5-c]pyridineC15H29NO2[α]D25=+2.7 (c 0.75, CH2Cl2)Source of chirality: d-mannitol, allyl Grignard reactionAbsolute configuration: (3aR,7S,7aR)

(3R,4R,5R)-1-Butyl-5-propylpiperidine-3,4-diolC12H25NO2[α]D25=+6.7 (c 0.3, EtOH)Source of chirality: d-mannitol, allyl Grignard reactionAbsolute configuration: (3R,4R,5R)

(S)-tert-Butyl 5-((S)-1,4-dioxaspiro[4.5]decan-2-yl)-5,6-dihydro-pyridine-1(2H)-carboxylateC18H29NO4[α]D25=+45.0 (c 0.9, CH2Cl2)Source of chirality: d-mannitol, vinyl Grignard reactionAbsolute configuration: (S,S)

(3S,4R,5S)-5-((S)-1,2-Dihydroxyethyl)piperidine-3,4-diolC7H15NO4[α]D25=-36.8 (c 0.95, MeOH)Source of chirality: d-mannitol, vinyl Grignard reaction, dihydroxylationAbsolute configuration: (3S,4R,5S)(S)

(3S,4R,5S)-tert-Butyl 3,4-dihydroxy-5-((S)-1,4-dioxaspiro[4.5]-decan-2-yl)piperidine-1-carboxylateC18H31NO6[α]D25=+5.7 (c 0.35, CH2Cl2)Source of chirality: d-mannitol, vinyl Grignard reaction, dihydroxylationAbsolute configuration: (3S,4R,5S)(S)