Amino-protecting groups subject to deblocking under conditions of nucleophilic addition to a Michael acceptor.: Structure-reactivity studies and use of the 2-(tert-butylsulfonyl)-2-propenyloxycarbonyl (Bspoc) group

A new type of amino-protecting group is described in which a Michael acceptor is incorporated into the protectant so that treatment with a nucleophile will trigger deblocking. Comparison of various Michael accepters showed that for several key electron-withdrawing groups, the order of reactivity was C6H5SO2 > Me3CSO2 > COOEt > CsH5SO > C(6)H(4)NO(2-)p. The reactivity of the nucleophile. (e.g., primary and secondary aliphatic amines) followed an order related to both intrinsic basicity and steric effects. beta-Substituents in the Michael acceptor caused significant retardation of the deblocking process. The Bspoc function was chosen for initial elaboration into a practical system for use in peptide synthesis. Bspoc amino acid chlorides were used as coupling agents and silica-tethered secondary amines as deblocking agents. With the latter, deblocking occurs cleanly and no byproducts remain in the organic solvent in which the deblocking is executed.