Topological mimicry of peptide β-turn secondary structures has been investigated using a 1,3,5,8-tetrasubstituted 1,3,4-benzotriazepin-2-one scaffold. Approaches were conceived for the synthesis of tetrasubstituted benzotriazepinones from 4-acetyl-3-aminobenzoate based on aza-amino acid chemistry and different orthogonal protection strategies. Installation of an 8position carboxylate on the aromatic ring enabled a diverse array of substituents to be introduced for mimicry of the i-position residue. Benzotriazepin-2-one crystallization and X-ray analysis demonstrated that in spite the absence of a stereogenic carbon center, the scaffold could serve as type I and I′ β-turn mimics, because pyramidalization of the N 3 -nitrogen in the benzotriazepin-2-one provides potential for adoptive chirality. 1,3,5,8-Tetrasubstituted 1,3,4-benzotriazepin-2-one scaffolds offer interesting potential for the cost-effective synthesis of nonpeptide β-turn surrogates for peptide mimicry in various recognition events.

N′-Alkyl hydrazides were effectively synthesized by routes featuring installation, alkylation, and removal of a trifluoroacetyl group. A set of amino acid derived hydrazides were acylated using trifluoroacetic anhydride, and the resulting trifluoroacetyl hydrazides were alkylated with alcohols in Mitsunobu reactions and with alkyl halides under alkaline conditions. Removal of the trifluoroacetyl group was affected under reductive and hydrolytic conditions to provide the respective N′-alkyl hydrazides. This three-step process may be performed without isolation of intermediates to yield N′-alkyl hydrazide after a single chromatographic purification.