Synthesis of four enantiomers of 2-acetamido-1-hydroxypropylphosphonates

Enantiomerically pure diethyl 2-acetamido-1-hydroxypropylphosphonates were synthesised from N-[(R)-(1-phenylethyl)]aziridine-(2S)- and N-[(S)-(1-phenylethyl)]aziridine-(2R)-carboxaldehydes via phosphonylation followed by acetylation of the hydroxy groups and the simultaneous hydrogenolytic cleavage of the aziridine rings and the removal of the chiral auxiliaries. In addition, enantiomerically pure diethyl (1S,2R)- and (1R,2S)-2-amino-1-hydroxypropylphosphonates (the phosphonate analogues of isothreonine) were separated.

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Diethyl (S)-hydroxy{(R)-1-[(S)-1-phenylethyl]aziridin-2-yl}methylphosphonateC15H24NO4PEe = 100%[α]D20=-15.2 (c 1.46, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration:(1S,2R,1′S)

Diethyl (R)-hydroxy{(R)-1-[(S)-1-phenylethyl]aziridin-2-yl}methylphosphonateC15H24NO4PEe = 100%[α]D20=-42.7 (c 1.27, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration:(1R,2R,1′S)

Diethyl (S)-hydroxy{(S)-1-[(S)-1-phenylethyl]aziridin-2-yl}methylphosphonateC15H24NO4PEe = 100%[α]D20=-54.7 (c 1.06, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration:(1S,2S,1′S)

Diethyl (1S,2R)-2-acetamido-1-hydroxypropylphosphonateC9H20NO5PEe = 100%[α]D20=+37.8 (c 1.04, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration:(1S,2R)

Diethyl (1S,2S)-2-acetamido-1-hydroxypropylphosphonateC9H20NO5PEe = 100%[α]D20=-19.4 (c 0.69, CHCl3)Source of chirality: (R)-1-phenylethylamineAbsolute configuration:(1S,2S)

Diethyl (1S,2R)-2-amino-1- hydroxypropylphosphonateC7H18NO4PEe = 100%[α]D20=+5.9 (c 1.08, CH3OH)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (1S,2R)