C-3 branched δ-3,5-cis- and trans-THF sugar amino acids: synthesis of the first generation of branched homooligomers

This article describes the efficient synthesis of the first generation of branched sugar amino acid (SAA) oligomers in solution phase via two main routes: by the use of a standard coupling reagent and via the use of active ester intermediates. Benzyl-protected dimeric carbopeptoid and methyl-protected dimeric and tetrameric, hexameric and octameric carbopeptoids were obtained from a branched delta-3,5-trans-tetrahydrofuran (THF) SAA and methyl-protected dimeric and tetrameric carbopeptoids were synthesised from a branched delta-3,5-cis-THF SAA. These systems are of interest because of their potential to display foldameric properties reminiscent of those observed in alpha-peptides and proteins. Amongst their many uses, foldamers provide simpler models in the study of the factors which induce the folding and unfolding of proteins and, ultimately, potential insights into their functioning.