Synthetic studies on threonines. The preparation of protected derivatives of D-allo- and L-allo-threonine for peptide synthesis

Article abstract of DOI:10.1016/S0040-4020(97)00059-8

N-Acetylated threonine derivatives, having tert-butyl or benzyl-based side-chain protection, form isolable 5(4H)-oxazalones on treatment with N-ethyl-N'-3-dimethylaminopropyl carbodiimide. N-chloroacetylated threonine derivatives, on the other hand, do not form oxazolones so readily. The N-acetylated oxazolones an easily epimerized and lead to diastereoisomeric mixtures of threonine derivatives on hydrolysis with dilute aqueous acid. The components of these mixtures can be separated chromatogaphically, but a useful alternative for the O-benzylated mixture is selective enzymatic hydrolysis using hog kidney acylase. These chemical transformations provide the basis for practical syntheses of protected derivatives of the non-proteinogenic allo-threonines, suitable for use in peptide synthesis.