Amino-protecting groups removable by neighboring-group assistance. II. The o-phenazophenoxyacetyl moiety

Abstract

The o-phenazophenoxyacety] moiety has been found to be an effective amino-protecting group for several amino esters. It can be introduced via acylation of the amino ester with an appropriate carboxylic acid. The removal of this blocking group was easily accomplished by reduction of the azo portion using potassium borohydride and palladium on carbon followed by acidification of the reaction mixture. An intramolecular rearrangement occurred which was followed by fragmentation into a benzoxazinone and the regenerated amino ester. Both the introduction and removal of this amino-protecting group were completed in higher yields than those obtained in previous procedures which employed the o-nitrophenoxyacetyl blocking group.

Protection Reactions

“…A similar process also cleaves 5b [8]. Nevertheless, incomplete reduction and cyclization steps have been the major concerns for a broad application of these groups in spite of selective and acceptable cleavage conditions.…”

Multistep deprotection for peptide chemistry

“…The general deprotection scheme and the representative list of amino-protecting groups (50-56) which are characterized by the ability to form cyclic lactams following reduction of the nitro or hydrazo group, thus releasing the amine or hydrazine moiety, are given in Fig. 35 (80,(85)(86)(87). Since the reduction of the nitro group is accomplished under rather harsh conditions, compounds 50-56 have found no practical application.…”