Synthesis of chimera oligopeptide including furanoid β-sugar amino acid derivatives with free OHs: mild but successful removal of the 1,2-O-isopropylidene from the building block

Complementary to hydrophobic five membered ring β-amino acids (e.g. ACPC), β-sugar amino acids (β-SAAs) have found increasing application as hydrophilic building blocks of foldamers and α/β chimeric peptides. Fmoc-protected β-SAAs [e.g. Fmoc-RibAFU(ip)-OH] are indeed useful Lego elements, ready to use for SPPS. The removal of 1,2-OH isopropylidene protecting group increasing the hydrophilicity of such SAA is presented here. We first used N(3)-RibAFU(ip)-OH model compound to optimize mild deprotection conditions. The formation of the 1,2-OH free product N(3)-RibAFU-OH and its methyl glycoside methyl ester, N(3)-RibAFU(Me)-OMe were monitored by RP-HPLC and found that either 50% TFA or 8 eqv. Amberlite IR-120 H(+) resin in MeOH are optimal reagents for the effective deprotection. These conditions were then successfully applied for the synthesis of chimeric oligopeptide: -GG-X-GG- [X=RibAFU(ip)]. We found the established conditions to be effective and—at the same time—sufficiently mild to remove 1,2-O-isopropylidene protection and thus, it is proposed to be used in the synthesis of oligo- and polypeptides of complex sequence combination. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00726-020-02923-3) contains supplementary material, which is available to authorized users.