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Solid-phase synthesis of cyclic hexapeptides wollamides A, B and desotamide B.

ABSTRACT: Solid-phase synthesis of antibacterial cyclohexapeptides including wollamides A, B and desotamide B has been developed. Briefly, the protected linear hexapeptides were assembled on 2-chlorotrityl chloride resin using standard Fmoc chemistry and diisopropylcarbodiimide/hydroxybenzotriazole coupling reagents, cleaved off-resin with hexafluoroisopropanol/dichloromethane to keep side-chain protecting groups intact, and cyclized in solution. Final global removal of all protecting groups using a cocktail of trifluoroacetic acid/triisopropylsilane/dichloromethane afforded the desired cyclic hexapeptides, which were characterized by 1H, 13C NMR, and HRMS. Subsequent investigation of macrocyclization parameters such as terminal residues, coupling reagents, and cyclization concentration revealed the optimized conditions for the synthesis of this class of cyclic hexapeptides.

SUBMITTER: Tsutsumi LS

PROVIDER: S-EPMC5678967 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Solid-phase synthesis of cyclic hexapeptides wollamides A, B and desotamide B.

Tsutsumi Lissa S LS Tan Ghee T GT Sun Dianqing D

Tetrahedron letters 20170525 27

Solid-phase synthesis of antibacterial cyclohexapeptides including wollamides A, B and desotamide B has been developed. Briefly, the protected linear hexapeptides were assembled on 2-chlorotrityl chloride resin using standard Fmoc chemistry and diisopropylcarbodiimide/hydroxybenzotriazole coupling reagents, cleaved off-resin with hexafluoroisopropanol/dichloromethane to keep side-chain protecting groups intact, and cyclized in solution. Final global removal of all protecting groups using a cockt ...[more]

PMID: 29129945

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