Application of Oppolzer's Sultam in the Synthesis of Cyclic alfa-Amino Acids and beta-Amino Acids

In this paper we describe the application of Oppolzer's sultam as a chiral auxiliary for the synthesis of cyclic α- and β 2 -amino acids. The key step of the synthesis is stereoselective alkylation of sultam-derived glycine and β-alanine Schiff's bases leading to diastereometrically pure products. Final compounds are obtained after mild acidic and next basic hydrolyses of auxiliary groups and can be directly converted into N-tert-butoxycarbonyl- or N-fluorenylmethoxycarbonyl derivatives useful in peptide synthesis. In the case of substrates alkylated with dihalogenoalkanes spontaneous cyclization occurring during removal of the auxiliary groups yields cyclic α-amino acids (proline homologues) with reasonable yield and stereoselectivity. Theoretical data explain the differences in tendency for cyclization between α- and β-amino acids.