Direct Peptide Cyclization and One-Pot Modification Using the MeDbz Linker

TY - JOUR

T1 - Direct Peptide Cyclization and One-Pot Modification Using the MeDbz Linker

AU - Gless, Bengt Herbert

AU - Olsen, Christian Adam

PY - 2018/9/7

Y1 - 2018/9/7

N2 - The one-pot synthesis and modification of cyclic peptides through a self-cleaving on-resin protocol is described. We apply Dawson's MeDbz linker to achieve direct intramolecular peptide cyclization by thioesterification followed by S → N acyl shift. This native chemical ligation approach requires no activating additive and allows direct modification of the crude cyclic peptides in one-pot. The strategy was applied to synthesize 5 cyclic peptide natural products of varying ring size. Finally, one-pot modifications include desulfurization, fluorophore conjugation, and intramolecular disulfide formation.

AB - The one-pot synthesis and modification of cyclic peptides through a self-cleaving on-resin protocol is described. We apply Dawson's MeDbz linker to achieve direct intramolecular peptide cyclization by thioesterification followed by S → N acyl shift. This native chemical ligation approach requires no activating additive and allows direct modification of the crude cyclic peptides in one-pot. The strategy was applied to synthesize 5 cyclic peptide natural products of varying ring size. Finally, one-pot modifications include desulfurization, fluorophore conjugation, and intramolecular disulfide formation.

U2 - 10.1021/acs.joc.8b01237

DO - 10.1021/acs.joc.8b01237

M3 - Letter

C2 - 30079722

SN - 0022-3263

VL - 83

SP - 10525

EP - 10534

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

IS - 17

ER -