Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. III: synthesis of enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-3,4,5-trihydroxycyclopentanecarboxylate

The first total synthesis of enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-3,4,5-trihydroxycyclopentanecarboxylate was carried out according to our recent novel strategy for the transformation of nitrohexofuranoses into cyclopentylamines, which is based on an intramolecular cyclization leading to 2-oxabicyclo[2.2.1]heptane derivatives. Differences in reactivity for this key step were rationalized by using molecular mechanism-based calculations.

Figure optionsDownload as PowerPoint slide

3,5-Di-O-benzyl-6-deoxy-6-nitro-d-glucono-1,4-lactoneC20H21NO7[α]D25=+17.9 (c 2.8, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (2R,3R,4R,5R)

Methyl 3,5-di-O-benzyl-6-deoxy-6-nitro-α-d-glucofuranosideC21H25NO7[α]D22=-6.0 (c 1.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,2R,3R,4R,5R)

Methyl 3,5-di-O-benzyl-6-deoxy-6-nitro-β-d-glucofuranosideC21H25NO7[α]D22=-77.0 (c 1.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,3R,4R,5R)

(1S,4S,5S,6R,7R)-6,7-Dibenzyloxy-5-nitro-2-oxabicyclo[2.2.1]heptan-3-oneC20H19NO6[α]D21=-35.0 (c 0.8, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,4S,5S,6R,7R)

(1S,3S,4S,5R,6R,7R)-6,7-Dibenzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptaneC21H23NO6[α]D22=-23.7 (c 1.2, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,3S,4S,5R,6R,7R)

(1S,3R,4S,5R,6R,7R)-6,7-Dibenzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptaneC21H23NO6[α]D19=-47.2 (c 1.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,3R,4S,5R,6R,7R)

Methyl (1S,2R,3S,4R,5S)-2,4-dibenzyloxy-3-hydroxy-5-nitrocyclopentanecarboxylateC21H23NO7[α]D21=+67.0 (c 1.4, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,2R,3S,4R,5S)

Methyl (1S,2S,3R,4S,5R)-2-benzyloxycarbonylamino-3,4,5-trihydroxycyclopentanecarboxylateC15H19NO7[α]D26=+125.5 (c 2.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,2S,3R,4S,5R)