Peptide-based drugs, despite being relegated as niche pharmaceuticals for years, are now capturing more and more attention from the scientific community. The main problem for these kinds of pharmacological compounds was the low degree of cellular uptake, which relegates the application of peptide-drugs to extracellular targets. In recent years, many new techniques have been developed in order to bypass the intrinsic problem of this kind of pharmaceuticals. One of these features is the use of stapled peptides. Stapled peptides consist of peptide chains that bring an external brace that force the peptide structure into an α-helical one. The cross-link is obtained by the linkage of the side chains of opportune-modified amino acids posed at the right distance inside the peptide chain. In this account, we report the main stapling methodologies currently employed or under development and the synthetic pathways involved in the amino acid modifications. Moreover, we report the results of two comparative studies upon different kinds of stapled-peptides, evaluating the properties given from each typology of staple to the target peptide and discussing the best choices for the use of this feature in peptide-drug synthesis.

The nitrosocarbonyls (R-CONO) are highly reactive species and remarkable intermediates toward different synthetic targets. This review will cover a research area whose impact in current organic synthesis is constantly increasing in the chemical community. This review represents the first and comprehensive picture on the generation and trapping of nitrosocarbonyls and is solidly built on more than 380 papers. Six different classes of key starting materials such as hydroxamic acids, N-hydroxy carbamates, N-hydroxyureas, nitrile oxides, and 1,2,4-oxadiazole-4-oxides were highlighted. The content of the review surveys all the methods to generate the nitrosocarbonyls through different approaches (oxidative, thermal, photochemical, catalytic, aerobic, and the less common ones) in the light of efficiency, yields, and mildness. The most successful trapping agents employed to catch these fleeting intermediates are reviewed, exploiting their superior dienophilic, enophilic, and electrophilic power. The work is completed by paragraphs dedicated to the detection of the intermediates, theoretical studies, and insights about the challenges and future directions for the field.

Constrained aminols from oxazanorbornene derivatives have the geometrical features to be used as β-turn inducers. Four different stereoisomers were prepared and spectroscopically characterized (MD calculations, NMR-titration and VT-NMR experiments). Temperature coefficients in DMSO are indicative for the existence of an intramolecular hydrogen bond. Chirooptical properties revealed a β-turn arrangement of all the synthesized compounds, where, depending on the absolute configuration of the cyclopentane spacer, they can be labeled as left- or right-handed turns.

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