To achieve the synthesis of head-to-tail cyclic peptides via the liquid-phase on-support cyclization and synergistic self-cleavage strategy, 4,4’-bis(diphenylphosphinyloxyl) diphenyl ketoxime (BDKO) and 4-diphenyl phospholoxy benzyl alcohol (DPBA) were designed and prepared as small-molecular supports for greener peptide synthesis. During liquid-phase peptide synthesis on BDKO (or DPBA) support for peptide chain extension by Boc protocol, the last amino acid at the N-terminus of the peptide chain ends with a Fmoc protected amino acid. With the removal of the Fmoc group, head-to-tail cyclization and self-cleavage of the peptide chain synchronously occurred on BDKO (or DPBA) support to release the target cyclic peptide and the original support itself. They can be easily separated and purified, and the support can be recycled for reusing directly. The total synthesis of naturally occurring cyclic peptides such as Mortiamide A-E, Gramicidin S and cyclo(Phe-Pro) on BDKO (or DPBA) support in a resin-free manner was successfully demonstrated.
Total Liquid-phase Sythesis, Head-to-tail Cyclization and Synergistic Self-cleavage of Peptide on Small-molecular Supports
30 June 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.