Ligation-Desulfurization at Thiol-Derived Amino Acids

3 Ligation-Desulfurization at Thiol-Derived Amino Acids 

Danishefsky and coworkers independently reported access to Val ligation junctions via a synthetic y-thiol Val building block 86 [100]. Using a ten-step 

Application of the Thr ligation strategy followed by radical desulfurization also enabled the synthesis of a glycopeptide bearing a complex A -linked hexasaccharide moiety [101]. 

A synthetic approach to both diastereomers of the Boc-protected y-thiol Pro derivative 94 was also reported by Otaka and coworkers [114]. The authors of this study confirmed the finding that use of the trans Pro derivative 94 was essential to facilitate ligation. The relative rate differential between rapid Cys-mediated ligations and ligation reactions mediated by trans y-thiol Pro residues was also exploited to effect a one-pot, dual kineticaUy controlled ligation reaction. 

This methodology strategically utilized an iV-sidfanylethylanilide (SEAlide) peptide as a latent thioester moiety (see [115] for more details on SEA peptide technologies) [114], 

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