Synthesis of 5-epi-deoxynojirimycin from methyl α-d-glucoside

A simple method for the preparation of 5-epi-nojirymycin (5-epi-DNJ) by a reductive amination of sugar derived alkoxyamines is presented. The latter were prepared in situ from the respective alkylated sugar oximes, which were obtained from the readily available methyl α-d-glucoside in a few well defined steps. The stereoselectivity of the reductive amination/cyclisation step depended on the size of the alkyl group in the oxime moiety and was best for the derivative decorated with a bulky tert-butoxyl group (5-epi-DNJ:DNJ = 82:18). The stereochemical outcome of this reaction was rather surprising since the analogous process performed for sugar alkylamines usually provides predominantly derivatives of DNJ.

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N-Methoxy-6-O-acetyl-2,3,4-tri-O-benzyl-1,5-dideoxy-1,5-imino-l-iditolC30H35NO6[α]D22 = +18.0 (c 1.0, CH2Cl2)Source of chirality: d-glucoseAbsolute configuration: (2S,3R,4R,5R)

N-Benzyloxy-6-O-acetyl-2,3,4-tri-O-benzyl-1,5-dideoxy-1,5-imino-l-iditolC36H39NO6[α]D22 = +9.9 (c 1.0, CH2Cl2)Source of chirality: d-glucoseAbsolute configuration: (2S,3R,4R,5R)

N-tert-Butoxy-6-O-acetyl-2,3,4-tri-O-benzyl-1,5-dideoxy-1,5-imino-l-iditolC33H41NO6[α]D22 = −3.5 (c 1.0, CH2Cl2)Source of chirality: d-glucoseAbsolute configuration: (2S,3R,4R,5R)

6-O-Acetyl-2,3,4-tri-O-benzyl-1,5-dideoxy-1,5-imino-d-glucitolC29H33NO5[α]D22 = +30.2 (c 1.0, CH2Cl2)Source of chirality: d-glucoseAbsolute configuration: (2S,3R,4R,5R)

6-O-Acetyl-2,3,4-tri-O-benzyl-1,5-dideoxy-1,5-imino-l-iditolC29H33NO5[α]D22 = −8.7 (c 1.0, CH2Cl2)Source of chirality: d-glucoseAbsolute configuration: (2S,3R,4R,5S)