α/β-Chimera peptide synthesis with cyclic β-sugar amino acids: the efficient coupling protocol.

The synthesis of α/β-chimeras comprises peptide bond formation from α- to β-, from β- to β-, and from β- to α-amino acid residues. The fine-tuned solid phase synthesis of -GXXG- chimera peptides containing the simplest achiral α-amino acid glycine and two cyclic SAAs of different ring size [X denoting cyclic β-Sugar Amino Acids (β-SAA)] is reported, variants containing Fmoc-RibAFU(ip)-OH a furanoid-, and Fmoc-GlcAPU(Me)-OH a pyranoid-type structural "Lego-element". Systematic search for the best coupling strategy with both H-β-SAA-OHs is described, including the comparison of the different coupling reagents and conditions. Selecting the optimal reagent (from commonly used PyBOP, HATU and HOBt) was assisted by time-resolved H-NMR: formation and stability of the Fmoc protected active esters were compared. We found that PyBOP is the best choice for successfully coupling both H-β-SAA-OH prototypes. The present comparative results open a reasonable route for building efficiently various -β-SAA- containing homo- and heterooligomers.