Enantiopure Fmoc-protected morpholine-3-carboxylic acidwas synthesized from dimethoxyacetaldehyde and serinemethyl ester through a short and practical synthetic route.The preparation consisted of a five-step process based onreductive amination, intramolecular acetalization, and concomitant elimination of the anomeric methoxy substituent,followed by hydrogenation of the double bond and finalacidic ester hydrolysis. The optical purity of both enantiomersof the title amino acid was demonstrated by HPLC analysisof the corresponding amide derivatives obtained fromcoupling with chiral (
S)-(-)-1-phenylethylamine. Moreover,the synthesis of a model tripeptide showed full compatibilityof the title Fmoc-amino acid with solid-phase peptidesynthesis, thus allowing the application of Fmoc-morpholine-3-carboxylic acid in peptidomimetic chemistry on the solidphase.
