Abstract: Conformationally restricted α -amino acids are valuable tools for studying the spatial requirements for receptor affinity and biological activity of natural amino acids. In this context, proline analogues possessing the characteristics of other amino acids (so-called chimeras) are of current interest. In addition, the conformationally rigid pyrrolidine fragment in their molecules stabilizes the substituents attached, moreover, in a certain spatial orientation with respect to each other. As a result, the conformational mobility of the entire molecule is restricted, thus enhancing the interaction between the pyrrolidine ligand and the active site of a protein target, as compared to an acyclic analogue. In a past decades, several analogues of proline chimeras with different stereochemistry and functionality at C-3 position have been synthesised (e.g Pro-Lys, Pro-Phe, Pro-Thr chimeras). While these analogues have proved useful for inducing specific constraints into amino acids and peptides, their structures do not permit additional derivatisation; a trait that is often required in drug discovery and lead optimisation. Polyfunctional proline-amino acid chimera may overcome these drawbacks. Our concept for developing such polyfunctional proline-amino acid chimeras employs the highly stereoselective intramolecular Michael reaction as a key step. Polysubstituted oxoprolines were prepared in two steps in high diastereomeric purity as all-trans stereoisomers. The required optically pure γ-oxo-α-aminoacids were prepared by reversible aza-Michael addition and/or multicomponent Mannich reaction using the crystallisation-induced asymmetric transformation (CIAT). The following acylation with maleic anhydride and highly diastereoselective intramolecular Michael reaction provided desired polysubstituted oxoprolines as single diastereomers.