An efficient approach to the synthesis of enantiomerically pure trans-1-amino-2-(hydroxymethyl)cyclopropanephosphonic acids

The synthesis of (1R,2S)- and (1S,2R)-1-amino-2-(hydroxymethyl)cyclopropanephosphonic acids was accomplished using different strategies. The (1R,2S)-stereoisomer could be efficiently obtained by the cyclopropanation of ethyl diethoxyphosphorylacetate with the cyclic sulfate derived from (S)-3-benzyloxy-1,2-propandiol as a key step. The (1S,2R)-stereoisomer was synthesized from a readily available (1S,5R)-3-oxabicyclo[3.1.0]hexan-2-on-1-phosphonate.

Figure optionsDownload as PowerPoint slide

Diethyl (−)-(1R,5S)-2-oxo-3-oxabicyclo[3.1.0]hexan-1-ylphosphonateC9H15O5P[α]D20=-49.7 (c 1.35, CHCl3)Source of chirality: resolutionAbsolute configuration: (−)-(1R,5S)

(+)-(1R,2S)-1-Amino-2-(hydroxymethyl)cyclopropylphosphonic acidC4H10NO4P[α]D20=+41.0 (c 1.00, H2O)Source of chirality: asymmetric synthesisAbsolute configuration: (+)-(1R,2S)