Building Units for N-Backbone Cyclic Peptides. 1. Synthesis of Protected N- (ω -Aminoalkylene)amino Acids and Their Incorporation into Dipeptide Units

A variety of new amino acids which contain an ω-aminoalkylene group on the N^α-amino nitrogen were synthesized by alkylation of alkylenediamines with α-halogeno acids. The reaction proceeds with inversion of configuration; thus, optically pure products were obtained when optically active α-halogeno acids were used. The N-(ω - aminoalkylene) amino acids were protected by orthogonal protecting groups to allow their incorporation into dipeptides by the “solution” techniques and into peptides by the solid-phase peptide synthesis (SPPS) methodology. A series of dipeptide analogs of Phe-Gly, Leu-Gly, Trp-Gly, Phe-Leu, and Phe-Ala in which the nitrogen of the peptide bond is alkylated by ω-aminoalkylene chains with various lengths were prepared. These new protected N-(ω-aminoalkylene)amino acids and their derived dipeptide units may be used as building blocks for conformationally constrained N-backbone cyclic peptides.