Conformational Analysis of 2-Substituted Cyclobutane-α-amino Acid Derivatives. A Synergistic Experimental and Computational Study

An extensive conformational study of different 2-substituted cyclobutane-α-amino acid derivatives in the solid state, in the gas phase, and in solution has been carried out. The study combines experimental techniques, such as X-ray diffraction and NMR spectroscopy, and computational methods, such as DFT calculations and molecular dynamics (MD) simulations, in a set solvent. The study reveals that the substituent at C2 in the cyclobutane ring, when fixed in an equatorial position, modulates the conformational preference of the ring-puckering.