Discovered by Kaiser and DeGrado in the early 80’s, Kaiser oxime resin possesses a unique labile oxime ester link that can be cleaved by aminolysis to release the peptide. As oxime ester linkage is stable to acidic, as well as to non nucleophilic basic conditions, anchoring linear peptides as an oxime ester bond allows peptide elongation on solid-support using Boc strategy. After N-Boc removal, the susceptibility of oxime resin to nucleophilic attack of the free amino terminal group allows the release of the peptide via acid-catalyzed N-terminal macrocyclization. Based on groundwork from our lab towards large peptide macrocycles, we will report our recent results on the chemical reactivity of the Kaiser oxime resin to prepare naturally occuring macrocyclic peptides, from pentapeptides to decapeptides, in a head-to-tail fashion. We will report also the first on-resin head-to-side chain concomitant cyclization/cleavage using orthogonally protected amino acids (Boc/Cbz) to prepare natural pseudacyclins A-E as well as schizopeptin 791 and anabaenopeptin NZ825 macrocyclic peptide phytochemicals.

Teaching an old dog a new trick: Oxime resin as versatile solid-support towards various cyclic peptides scaffolds

256th National Meeting (2018)

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