(+)- and (-)-2-aminocyclobutane-1-carboxylic acids and their incorporation into highly rigid beta-peptides: stereoselective synthesis and a structural study.
[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.
Izquierdo
Sandra
S
Departament de Química, Servei de RMN, and Unitat de Cristallografia, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain.
Rúa
Federico
F
Sbai
Abdelouahid
A
Parella
Teodor
T
Alvarez-Larena
Angel
A
Branchadell
Vicenç
V
Ortuño
Rosa M
RM
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
D000596:Amino Acids; D002264:Carboxylic Acids; D003503:Cyclobutanes; D010455:Peptides