Staudinger Ligation Using Solid-Supported Phosphinethiol

Significance

Staudinger ligation using a core-shell-type resin-supported phosphinothiol 1 was developed as a tool for facile condensation of small peptides. Thus, the dipeptide (Fmoc-Phe-Phe-OH) was assembled by solid-phase peptide synthesis on 1. The solid-phase Staudinger ligations were performed between 2 and 15 different azido acids derived from Gly, Ala, Leu, Ile, Val, Phe, Asn, Gln, Asp(t-Bu), Ser(t-Bu), Thr(t-Bu), Met, Lys(t-Boc), Tyr(t-Bu), and His to give the corresponding tripeptides 4 in quantitative yields along with resin-bound phosphine oxide 3. Compound 3 was recovered by simple filtration and reduced with an excess of trichlorosilane to regenerate compound 1. Performance of recycled 1 was not changed after five times in terms of the ligation yield and the purity of the product.