Expansion of Phosphane Treasure Box for Staudinger Peptide Ligation

A smooth traceless ligation strategy
using an air-stable phosphane
probe (2-(diphenylphosphanyl)­phenyl)­methanol as a C-terminus activator
has been demonstrated at simple and sterically hindered amino acid
junctions (Gly, Ala, Trp, Glu). This Staudinger peptide ligation proceeds
via formation of a seven-membered transition state to afford di-,
tetra-, and pentapeptides in 78–95% yields. The experimental
results of ligation at Gly junction and regioselective ligation at
Glu junction were theoretically studied by computational calculations.
These findings established the versatile behavior of our synthesized
phosphane probe for Staudinger peptide ligation toward synthesizing
peptides and proteins of choice.