β-Peptides incorporating polyhydroxylated cyclohexane β-amino acid: synthesis and conformational study.

We describe the synthesis of trihydroxylated cyclohexane β-amino acids from (-)-shikimic acid, in their and configuration, and the incorporation of the isomer into a -2-aminocyclohexanecarboxylic acid peptide chain. Subsequently, the hydroxyl groups were partially or totally deprotected. The structural study of the new peptides by FTIR, CD, solution NMR and DFT calculations revealed that they all fold into a 14-helix secondary structure, similarly to the homooligomer of -2-aminocyclohexanecarboxylic acid.

Stable D-xylose ditriflate in divergent syntheses of dihydroxy prolines, pyrrolidines, tetrahydrofuran-2-carboxylic acids, and cyclic β-amino acids.

Double nucleophilic displacement of D-xylo-ditriflate by amines, water and alkyl cyanoacetates, respectively, gave a series of bicyclic divergent intermediates for the synthesis of a wide range of highly functionalized targets, including hydroxylated prolines, pyrrolidines, furanoic acids, and cyclopentanes.

Polyhydroxylated Cyclopentane β-Amino Acids Derived from d-Mannose and d-Galactose: Synthesis and Protocol for Incorporation into Peptides.

A stereoselective synthesis of polyhydroxylated cyclopentane β-amino acids from hexoses is reported. The reaction sequence comprises, as key steps, ring-closing metathesis of a polysubstituted diene intermediate followed by the stereoselective aza-Michael functionalization of the resulting cyclopent-1-ene-1-carboxylic acid ester. Examples of synthesis of polysubstituted 2-aminocyclopentanecarboxylic acid derivatives starting from protected d-mannose and d-galactose are presented.

Environmental Effects Determine the Structure of Potential β-Amino Acid Based Foldamers.

This work shows that hybrid peptides formed by alternating trans-2-aminocyclopentanecarboxylic acid (trans-ACPC) and trans-2-aminocyclohexanecarboxylic acid (trans-ACHC) do not fold in the solvents typically used in the study of their homo-oligomers. Only when the peptides are assayed in SDS micelles are the predicted helical structures obtained. This indicates that the environment could play an equally important role (as the backbone stereochemistry) in determining their fold, possibly by providing a sequestered environment.