Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. IV: Synthesis of enantiopure methyl (1S,2R,3R,4R,5S)-5-benzyloxycarbonylamino-2,3-isopropylidenedioxy-4-methoxycyclopentanecarboxylate

The first total synthesis of a new enantiopure polyhydroxylated cyclopentyl β-amino acid [methyl (1S,2R,3S,4R,5S)-2-benzyloxy-5-benzyloxycarbonylamino-3-hydroxy-4-methoxycyclopentanecarboxylate] was achieved according to our recent novel strategy for the transformation of nitrohexofuranoses into cyclopentylamines. This approach is based on an intramolecular cyclization leading to 2-oxabicyclo[2.2.1]heptane derivatives. Epimerization of this amino acid derivative to methyl (1S,2R,3R,4R,5S)-2-benzyloxy-5-benzyloxycarbonylamino-3-hydroxy-4-methoxycyclopentanecarboxylate constitutes the first example of the preparation of one of the members of this family of amino acids with a stereochemistry that is not compatible with the above key cyclization step.

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3-O-Benzyl-6-O-(tert-butyldiphenylsilyl)-1,2-O-isopropylidene-α-d-glucofuranoseC32H40O6Si[α]D24=-25.0 (c 2.2, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

3-O-Benzyl-6-O-(tert-butyldiphenylsilyl)-1,2-O-isopropylidene-5-O-methyl-α-d-glucofuranoseC33H42O6Si[α]D24=-18.7 (c 1.9, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

3-O-Benzyl-1,2-O-isopropylidene-5-O-methyl-α-d-glucofuranoseC33H42O6Si[α]D24=-28.5 (c 1.3, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

3-O-Benzyl-6-deoxy-6-iodo-1,2-O-isopropylidene-5-O-methyl-α-d-glucofuranoseC17H23IO5[α]D25=-55.6 (c 2.2, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4S,5S)

3-O-Benzyl-6-deoxy-1,2-O-isopropylidene-5-O-methyl-6-nitro-α-d-glucofuranoseC17H23NO7[α]D25=-46.4 (c 1.1, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3S,4R,5R)

3-O-Benzyl-6-deoxy-5-O-methyl-6-nitro-d-glucono-1,4-lactoneC14H17NO7[α]D25=+25.3 (c 1.8, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (2R,3R,4R,5R)

(1S,4S,5S,6R,7R)-7-Benzyloxy-6-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptan-3-oneC14H15NO6[α]D27=-63.7 (c 1.4, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,4S,5S,6R,7R)

Methyl (1S,2R,3S,4R,5S)-2-benzyloxy-5-benzyloxycarbonylamino-3-hydroxy-4-methoxycyclopentanecarboxylateC23H27NO7[α]D26=-33.5 (c 2.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,2R,3S,4R,5S)

Methyl (1S,2R,3R,4R,5S)-2-benzyloxy-5-benzyloxycarbonylamino-3-hydroxy-4-methoxycyclopentanecarboxylateC23H27NO7[α]D22=-44.9 (c 1.1, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,2R,3R,4R,5S)

Methyl (1S,2R,3R,4R,5S)-5-benzyloxycarbonylamino-2,3-isopropylidenedioxy-4-methoxycyclopentanecarboxylateC19H25NO7[α]D17=-74.6 (c 1.2, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,2R,3R,4R,5S)