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

Abstract

N-Acetylated threonine derivatives, having tert-butyl or benzyl-based side-chain protection, form isolable 5(4H)-oxazolones 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 are easily epimerized and lead to diastereoisomeric mixtures of threonine derivatives on hydrolysis with dilute aqueous acid. The components of these mixtures can be separated chromatographically, 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.