Enantiomeric inclusion of α-hydroxy esters by (R)-(1-naphthyl)glycyl- (R)-phenylglycine and the crystal structures of the inclusion cavities

Article abstract of DOI:10.1021/jo9818778

A simple dipeptide, (R)-(1-naphthyl)glycyl-(R)-phenylglycine [(R,R)-1], formed inclusion compounds with several α-hydroxy esters (2) with high enantioselectivity. By crystallization of a mixture of the dipeptide [(R,R)- 1] and racemic 2a [MeCH(OH)COOMe] from methanol, asymmetric recognition occurred to give an inclusion compound that contains the S form of 2a in 89% ee. X-ray crystallographic study of the inclusion compound elucidated that the dipeptide molecules arrange in a 'folded antiparallel' β-sheetlike structure to accommodate the α-hydroxy ester in the pocket-type cavity surrounded by naphthyl and phenyl groups on the sheet. Similarly, 2b [MeCH(OH)-COOEt] and 2f [dihydro-3-hydroxy-4,4-dimethyl-2(3H)-furanone] were included with high enantioselectivity of the S form. When bulkier 21 [t- BuCH(OH)COOMe] was used as a guest molecule, the arrangement of dipeptide molecules changed to an 'extended antiparallel' mode, where the naphthyl and phenyl groups arranged in a 'parallel stacked and displaced' mode and a channel-type cavity was constructed. The guest molecules were accommodated via hydrogen bonding in the channel-type cavity with high enantioselectivity of the S form (82% ee). In the case of 2k [i-PrCH-(OH)COOMe], optically pure (S)-2k formed the dipeptide sheet with the 'folded antiparallel' structure by cocrystallization with (R,R)-1, while the 'extended antiparallel' structure appeared in the inclusion of racemic 2k.