A method for the one-pot regioselective formation of the two disulfide bonds of alpha-conotoxin SI

A one-pot method for the regioselective formation of the disulfide bridges of rx-conotoxin SI employing temperature-controlled orthogonal protecting g roups is reported. The pairing of t-butyl and 4-methylbenzyl sidechain prot ecting groups was chosen for the four cysteine residues. Cleavage of the pe ptide from a solid support afforded a fully S-protected crude product. The first disulfide bridge was formed directly from the crude material by simul taneous cleavage and oxidation of the t-butyl groups in TFA:DMSO:anisole (9 7.9:2:0.1) at room temperature. The subsequent heating of this solution res ulted in the cleavage of the 4-methylbenzyl groups with simultaneous oxidat ion yielding the desired bicyclic product. (C) 2000 Elsevier Science Ltd. A ll rights reserved.