Studies on the stereocontrolled transformation of nitrohexofuranoses into 2-oxabicyclo[2.2.1]heptanes. V: Synthesis of enantiopure methyl (1R,2R,4S)-2-amino-4-hydroxycyclopentanecarboxylate

The first total synthesis of enantiopure methyl (1R,2R,4S)-2-amino-4-hydroxycyclopentanecarboxylate was carried out according to our recent novel strategy for the transformation of nitrohexofuranoses into cyclopentylamines, which is based on an intramolecular cyclisation leading to 2-oxabicyclo[2.2.1]heptane derivatives. It was observed that one of the substrate anomers produces an elimination rather than a cyclisation reaction. These and other differences in the reaction paths for this key step were rationalised by means of molecular mechanism based calculations.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

3,5-Dideoxy-6-nitromethyl-d-xylono-1,4-lactoneC6H9NO5[α]D25=+92.0 (c 0.7, MeOH)Source of asymmetry: d-glucoseAbsolute configuration: (2R,4R)

(3R,5S)-3-Methoxy-5-nitro-2-oxabicycle[2.2.1]heptaneC7H11NO4[α]D22=-4.9 (c 1.1, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,3R,4R,5R)

(2S,5R)-2-Methoxy-5-(2-nitroethyl)-2,5-dihydrofuraneC7H11NO4[α]D20=-8.7 (c 0.6, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1S,5R)

(1R,2R,4S)-Methyl 4-hydroxy-2-nitrocyclopentanecarboxylateC7H11NO5[α]D20=-53.2 (c 0.5, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,4S)

(1R,2R,4S)-Methyl 2-amino-4-hydroxycyclopentanecarboxylateC7H13NO3[α]D20=-28.5 (c 2.0, CHCl3)Source of asymmetry: d-glucoseAbsolute configuration: (1R,2R,4S)