Peptide Synthesis by Prior Thiol Capture. 2. Design of Templates for Intramolecular O,N-Acyl Transfer. 4,6-Disubstituted Dibenzofurans as Optimal Spacing Elements

Article abstract of DOI:10.1021/jo00360a033

A central feature of the strategy for amide bond formation by prior thiol capture is an intramolecular acyl transfer across a template that links the phenolic ester function of one peptide with an unsymmetrical disulfide involving the side chain of the N-terminal cysteine residue of a second peptide.The structures of the 4-hydroxy-6-mercaptodibenzofuran (3) and 4-hydroxy-6-mercaptophenoxythiin (4) are established by 1H NMR spectra of deuterated dibenzofuran and phenoxythiin derivatives.On the basis of the criterion of effective molarity, a dibenzofuran template for intramolecular acyl transfer is shown to be approximately 2 orders of magnitude more efficient than a phenoxythiin.An effective local concentration of ca. 5 M and a Hammett ρ value of 2.6 are observed for the intramolecular acyl-transfer reaction 1 -> 2.