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. Method:: The interaction mechanism of the two enantiomers of α-phenylethanol with β-CD was investigated using 1H-NMR and ROESY. The loading of β-cyclodextrin (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 was 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 oriented more toward the small-port end of β-CD than that of the R-enantiomer, which was reflected in the signals of 2D ROESY, which were obviously different. Conclusion:: β-CD can enantioselectively recognize the α-phenylethanol enantiomers, and the 2D ROESY method is a very direct and powerful tool in the recognition process of chiral host and guest research.