Enantioselective Recognition of Chiral Α-Phenylethanol by Β-Cyclodextrin and Characterization of its Inclusion Behaviour based on 2D ROESY

Background: α-phenylethanol and its derivatives are important intermediates for the synthesis of a variety of chiral drugs. Methods: The interaction mechanism of the two enantiomers of α-phenylethanol with β-cyclodextrin (β-CD) was investigated using 1H-NMR and ROESY. The loading of β-CD as the host with the chiral drug intermediate α-phenylethanol as the guest was investigated using high-resolution NMR in D2O and quantum chemical calculations. Results: The results showed that both α-phenylethanol enantiomers were able to enter into the hydrophobic cavity of β-CD and undergo enantiospecific interactions, while the combination of 2D ROESY and quantum chemical calculations showed that the benzene ring of both R and S α- phenylethanol were inserted into the β-CD cavity toward the small-port end. However, the most stable poses of the two enantiomers were different, so the benzene ring of the S-enantiomer was more inclined to position the small-port end of β-CD than that of the R-enantiomer, which was reflected differently in the signals of 2D ROESY. Conclusion: β-CD can enantioselectively recognize the α-phenylethanol enantiomers, and the 2D ROESY method is a direct and powerful tool in the recognition process of chiral host and guest research.