Diastereoselective synthesis of delta-aminoacids through domino Ireland-Claisen rearrangement and Michael addition.

A novel domino reaction--stereoselective Ireland-Claisen rearrangement and asymmetric Michael addition--is described. A protocol starting from Baylis-Hillman adducts 3a-f using chiral lithium amide affords optically active gamma-substituted delta-amino acids 4a-f with high diastereoselectivities and enantioselectivities. The acid can be isolated easily from large-scale reactions and transformed to 2,3-disubstituted piperidines 11 or 2-substituted nipecotic acid derivates 12.

A convenient asymmetric synthesis of a beta-amino ester with additional functionalization as a precursor for peptide nucleic acid (PNA) monomers.

We report the asymmetric synthesis of di-3-pentyl (3S,alphaS,7E)-3-N-benzyl-N-alpha-methylbenzylamino-dec-7-enedioate (9), which contains the correct functionalization to produce delta-amino acid derivatives to be used as monomers for Peptide Nucleic Acid (PNA) formation With this aim, thymine-pentanoic acid 15 and some of its ester derivatives were obtained, their reactivity was studied and the noteworthy ethyl ester 12 was quantitatively produced by transesterification of methyl ester 11, thus paving the way for the synthesis of the thymine-containing amino ester IV, which has been designed as a building block for a Nucleic-Acid analog with a chiral, flexible peptide backbone.