10.1021/ol034168b
The research focuses on the development of a bowl-shaped C3-symmetric receptor (1a) with a concave phosphine oxide functionality within its molecular bowl, designed to exhibit remarkable selectivity for asparagine (Asn) derivatives. The purpose of this study was to construct a host molecule with a rigidly defined cavity that could mimic the active site of enzymes, thereby functioning as a reaction or binding site with unique properties. The researchers synthesized 1a and 1b, starting with the trialkylation of tris(chloromethyl)phosphine oxide with dimethyl 5-mercaptoisophthalate, followed by an intermolecular macrolactamization process. The conclusions drawn from the study indicate that 1a showed a high residue selectivity for Asn alkyl amide against other amino acid derivatives like Gln, Glu, and Asp, which have similar H-bond donor/acceptor geometries. This selectivity was attributed to the cooperative hydrogen bonding between the phosphine oxide in the cavity of 1a and the guest molecules, along with subtle differences in the intermolecular hydrogen bonding mode within the cavity. The chemicals used in the synthesis process included tris(chloromethyl)phosphine oxide, dimethyl 5-mercaptoisophthalate, and (1R,2R)-diaminocyclohexane, among others.
Xn
