Peptides containing 4-amino-1,2-dithiolane-4-carboxylic acid (Adt): conformation of Boc-Adt-Adt-NHMe and NH...S interactions

To study the conformational preferences induced by the insertion of the 4-amino-1,2-dithiolane-4-carboxylic acid (Adt) residue into a peptide backbone, the achiral N-protected dipeptide methylamide Boc-Adt-Adt-NHMe (1) was synthesized and its crystal state and solution conformation studied and compared with that exhibited by its carba-analogue Boc-Ac(5)c-Ac(5)c-NHMe containing two residues of 1-aminocyclopentane-1-carboxylic acid (Ac(5)c). Compound 1 in the crystal adopts a type-III beta-turn conformation and an analogous structure is that preferred in chloroform solution as established by H-1-NMR and NOE information. In the crystal packing three different Adt rings form a cavity and the involved sulphur atoms give rise to unusual multiple interactions with one NH group. The chemical nature of these intermolecular and intramolecular main-chain(...)side-chain (NHS)-S-... interactions are discussed in terms of quantum chemical calculations.