title: (+)- and (-)-2-aminocyclobutane-1-carboxylic acids and their incorporation into highly rigid beta-peptides: stereoselective synthesis and a structural study.
abstract: [Chemical reaction: See text] Several derivatives of (+)- and (-)-2-aminocyclobutane-1-carboxylic acid, 1, have been prepared through enantiodivergent synthetic sequences. The stereoselective synthesis of free amino acid (+)-1 has been achieved, and this product has been fully characterized for the first time. Stereocontrolled alternative synthetic methodologies have been developed for the preparation of bis(cyclobutane) beta-dipeptides in high yields. Among them, enantio and diastereomers have been synthesized. beta,beta- and beta,delta-Dimers resulting from the coupling of a cyclobutane residue and a linear amino acid have also been prepared. The ability of the cyclobutane ring as a structure-promoting unit both in the monomers and in the dimers has been manifested. The NMR structural study and DFT theoretical calculations evidence the formation of strong intramolecular hydrogen bonds giving rise to cis-fused [4.2.0]octane structural units that confer high rigidity on these molecules both in solution and in the gas phase. The contribution of a cis-trans conformational equilibrium derived from the rotation around the carbamate N-C(O) bond has also been observed, the trans form being the major conformer. In the solid state, this equilibrium does not exist, and moreover, intermolecular hydrogen bonds are present.
authors.affiliation: Departament de Química, Servei de RMN, and Unitat de Cristallografia, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Izquierdo
authors.forename: Federico
authors.initials: F
authors.lastname: Rúa
authors.forename: Abdelouahid
authors.initials: A
authors.lastname: Sbai
authors.forename: Teodor
authors.initials: T
authors.lastname: Parella
authors.forename: Angel
authors.initials: A
authors.lastname: Alvarez-Larena
authors.forename: Vicenç
authors.initials: V
authors.lastname: Branchadell
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Ortuño
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry; D003503:Cyclobutanes / Q000737:chemistry*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D002264:Carboxylic Acids; D003503:Cyclobutanes; D010455:Peptides