Synthesis of a building block for a nucleic-acid analog with a chiral, flexible peptide backbone

We present here a nine-step synthesis of the thymine-containing amino ester 1, starting from commercially available methyl N-[(tert-butoxy)carbonyl]-L-serinate. Amino ester 1 is considered as a building block for the preparation of a new nucleic-acid analog with a chiral, flexible polyamide backbone, Key steps in the synthesis are the vitamin-B-12-catalyzed addition of 3-bromo-N-[(tert-butoxy)carbonyl]-L-alaninate 2 to ethyl acrylate and the homologation of the corresponding N-protected alpha-amino acid 4 into the beta-amino ester 6 by Arndt-Eistert chemistry. The latter was found to proceed with 10% inversion of configuration at the asymmetric center in 6. Resolution to enantiomerically pure material, however, was easily achieved by simple crystallization of 1.