C-alpha-Hydroxymethyl methionine: synthesis, optical resolution and crystal structure of its (+)-N-alpha-benzoyl derivative

(R,S)-Methionine was transformed into C-alpha-hydroxymethyl methionine by a route involving C-alpha-hydroxymethylation of 2-phenyl-4-methylthioethyl-5-oxo-4,5-dihydro-1,3-oxazole. The absolute configuration of (-)-C-alpha-hydroxymethyl methionine was elucidated to be (S) by chemical correlation with (S) (-)-C-alpha-ethyl serine. Absolute structure determination (by single crystal X-ray diffraction) on N-alpha-benzoyl-C-alpha-hydroxymethyl methionine confirmed the (R)-configuration for the (+)-enantiomer. In addition, the X-ray diffraction analysis showed that the C-alpha,C-alpha-disubstituted glycyl residue adopts the fully extended (C-5) conformation.