A Passerini condensation of acyl cyanides, carboxylic acids, and isonitriles has been developed that affords efficient access to functionalized diamides as well as beta-peptides of alpha-hydroxy-beta-amino acids. Such compounds are protease-resistant and form stable helical and sheet structures when incorporated into larger peptides. N-Protected alpha-amino acids and isocyanoesters derived from alpha-amino acids participate in the condensation, leading to alpha/beta peptides embodying the heterogeneous alpha/beta/alpha backbone motif, recent examples of which display antibiotic activity.

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Melting points were uncorrected. 1 H NMR (500 MHz) and 13 C NMR (125 MHz) were taken on a Varian Inova-500 spectrometer using CDCl 3 as solvent. Spectra were referenced to residual CHCl 3 (7.26 ppm for 1 H NMR) and CDCl 3 (77.0 ppm for 13 C NMR). Heteronuclear single quantum correlation (HSQC) and heteronuclear multiple bond correlation (HMBC) spectra were obtained on a Varian Inova-600 spectrometer using CDCl 3 as solvent. IR spectra were obtained on a Perkin-Elmer 16PC FT-IR spectrometer. Chemicals were obtained from Aldrich and Lancaster and used as received unless specified. Raney® 2800 nickel (Aldrich) was washed 3x with water to pH 7. Methanol was distilled from magnesium methoxide. Methylene chloride was distilled from CaH 2 . In reactions leading to diastereomers, spectroscopic data were reported for mixtures, unless specified otherwise.Representative procedure for the condensation of acyl cyanides, isonitriles and carboxylic acids.