2-Phenyl-tetrahydropyrimidine-4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β2-amino acids

Abstract

Novel procedures have been developed to condense benzaldehyde effectively with β-amino acid amides to cyclic benzyl aminals. Double carbamate protection of the heterocycle resulted in fully protected chiral β-alanine derivatives. These serve as universal precursors for the asymmetric synthesis of functionalised β2-amino acids containing acid-labile protected side chains. Diastereoselective alkylation of the tetrahydropyrimidinone is followed by a chemoselective two step degradation of the heterocycle to release the free β2-amino acid. In the course of this study, an L-asparagine derivative was condensed with benzaldehyde and subsequently converted to orthogonally protected (R)-β2-homoaspartate.

Keywords

• β2-amino acids
• cyclocondensation
• diastereoselective alkylation
• N,N-acetals
• peptidomimetics
• ring opening
• self-regeneration of stereocentres (SRS)