(+)- and (−)-2-Aminocyclobutane-1-carboxylic Acids and Their Incorporation into Highly Rigid β-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.

Benzyl Alcohol Oxidation on Carbon‐Supported Pd Nanoparticles: Elucidating the Reaction Mechanism

“…In contrast, the C‐terminal residue has equatorial C=O and axial NH groups ( θ = 61°), and participates in intermolecular hydrogen bonds, which result in infinite sheet‐like interactions along the crystallographic b axis. The hydrogen‐bonded packing pattern for 6 is different from those reported previously for homodimers of cis ‐2‐aminocycloalkanecarboxylic acids in the crystal state 20,21. The direction of the N‐ to the C‐terminus of 6 alternates along the packing direction, whereas cis ‐ACBC20 and cis ‐ACPC dimers21 are packed parallel along the direction of intermolecular hydrogen bonding.…”

Enantioselective Template‐Directed [2+2] Photocycloadditions of Isoquinolones: Scope, Mechanism and Synthetic Applications

“…In an extension to our photocycloaddition methodology, we wanted to expand the range of available products through further synthetic transformations of the photoadducts. To this end, we found that cyclobutyl ester 7 h (EWG=CO 2 t Bu) is a particularly useful photoproduct, which can be selectively transformed in excellent yield into the corresponding free acid 14 23 or alcohol 15 (Scheme ).…”

Cyclic Beta-Amino Acids as Conformational Constraints

“…Short peptide sequence like dipeptide sequences containing trans-AC 4 C formed an eight-membered hydrogen bond 3 2. 33 but longer sequences(such as hexamer and octamer) of the trans-A~C were stabilized through a 12-membered hydrogen bond and adopted a 12-helical conformation both in the solid state and in the solution 34 • The aza analogue of the ACC was also synthesized on the assumption that it would behave similarly like ACC 56 • Further, it was hypothesized that the additional nitrogen atom in the ring could act as a hydrogen bond acceptor that could provide the extra stability in the peptides nucleating different folds. There is another example of a four membered P-amino acid that contains an oxetane ring 57 • The peptide hexamer ( Figure 6) containing this amino acid gave a 1 0-helix in solution as confirmed by 2D NMR studies.…”