Peptide Synthesis by Prior Thiol Capture. 1. A Convenient Synthesis of 4-Hydroxy-6-mercaptodibenzofuran and Novel Solid-Phase Synthesis of Peptide-Derived 4-(Acyloxy)-6-mercaptodibenzofurans

Article abstract of DOI:10.1021/jo00360a032

Peptide bond formation by intramolecular acyl transfer across a rigid template is outlined.The template precursor 6-hydroxy-4-mercaptodibenzofuran (3) is obtained from 4-methoxydibenzofuran by metalation with n-butyllithium, oxidation with elemental sulfur, and demethylation.Routes to 4-(acyloxy)-6-mercaptodibenzofurans 4 are reported.Esters 4 derived from simple urethane N-blocked α-amino acids are conveniently prepared by direct acylation of 6-hydroxy-4-(methoxycarbonyldithio)dibenzofuran (12), followed by reduction with tri-n-butylphosphine.Esters 4 derived from the C-terminal carboxyl groups of peptides are prepared by a novel variant of conventional solid-phase peptide synthesis in which the chain elongation steps are carried out on the 4-((α-aminoacyl)oxy)-6-dibenzo-furanyldithio function linked through the disulfide to a polymeric support.At the completion of the elongation steps, release of 4 from the resin is achieved by reduction of the disulfide bond with tri-n-butylphosphine.