| Abstract
| - The traceless Staudinger ligation is an effective means to synthesize an amide bond betweentwo groups of otherwise orthogonal reactivity: a phosphinothioester and an azide. An important applicationof the Staudinger ligation is in the ligation of peptides at a variety of residues. Here, we demonstrate thatthe traceless Staudinger ligation can be achieved in water with a water-soluble reagent. Those reagentsthat provide a high yield of amide product discourage protonation of the nitrogen in the key iminophosphoraneintermediate. The most efficacious reagent, bis(p-dimethylaminoethyl)phosphinomethanethiol, mediatesthe rapid ligation of equimolar substrates in water. This reagent is also able to perform a transthioesterificationreaction with the thioester intermediate formed during intein-mediated protein splicing. Hence, the tracelessStaudinger ligation can be integrated with expressed protein ligation, extending the reach of modern proteinchemistry.
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