Two‐step hard acid deprotection/cleavage procedure for solid phase peptide synthesis

Abstract
A new two‐step deprotection/cleavage procedure for t‐butoxycarbonyl (Boc) based solid phase peptide synthesis is reported. First the protective groups are removed from 4‐(oxymethyl)‐phenylacetamidomethyl (PAM) resin attached peptide with the weak hard acid, trimethylsilyl bromide‐thioanisole/trifluoroacetic acid (TFA). In the second step, the peptide is cleaved from the resin with a stronger hard acid such as trimethylsilvl trifluoromethanesulfonate in TFA or with HF. The method is also shown to deformylate Nin‐formyltryptophan moiety efficiently. The usefulness of this procedure for practical solid phase peptide synthesis is demonstrated by comparison with other deprotection methods in the synthesis of urotensin II and human endothelin.

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