Synthesis of substituted β-amino-acids and their utilisation in peptide formation

The dihydro-oxazinone derivatives of some N-benzoyl substituted β-amino~acids have been prepared and their potential as intermediates in the synthesis of sterically hindered β-peptides has been investigated. The work was prompted by the analogous use of oxazolones for the synthesis of sterically hindered ∝ -amino-acid peptides. In view of the ready accessibility of β-isovalerolactam,
some N-protected derivatives have been prepared and their potential in peptide synthesis has also been studied.
Linear tri- and hexapeptides of β-aminopivalic acid have been synthesised, the former by two different routes. The effect of steric hindrance at the carboxyl function of this amino-acid with respect to conventional coupling methods has been found to be less profound than the effect of similar steric hindrance at the amino function as exhibited by β-amino-isovaleric acid. The cyclotri- and cyclohexapeptides of β-aminopivalic acid have been prepared from their respective linear peptides; the latter has also been obtained from the linear tripeptide by cyclodimerisation. They were both characterised by their mass spectra and elemental analysis.
An extensive investigation of dihydro-oxazinone-N-acyl-β-lactam isomerism has been carried out to solve a problem of structure which arose in the chemical literature between different groups of workers. This includes the hydrogenolysis of dihydro-oxazinones to give substituted B-aminopropionals.