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

Markus Nahrwold; Arvydas Stoncius; Anna Penner; Beate Neumann; Hans-Georg Stammler; Norbert Sewald

doi:10.3762/bjoc.5.43

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

Beilstein J Org Chem. 2009 Sep 14:5:43. doi: 10.3762/bjoc.5.43.

Authors

Markus Nahrwold¹, Arvydas Stoncius, Anna Penner, Beate Neumann, Hans-Georg Stammler, Norbert Sewald

Affiliation

¹ Bielefeld University, Department of Chemistry, Organic and Bioorganic Chemistry, Universitätsstr. 25, 33615 Bielefeld, Germany.

Abstract

Novel procedures have been developed to condense benzaldehyde effectively with beta-amino acid amides to cyclic benzyl aminals. Double carbamate protection of the heterocycle resulted in fully protected chiral beta-alanine derivatives. These serve as universal precursors for the asymmetric synthesis of functionalised beta(2)-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 beta(2)-amino acid. In the course of this study, an L-asparagine derivative was condensed with benzaldehyde and subsequently converted to orthogonally protected (R)-beta(2)-homoaspartate.

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