A novel optically active host: design, computer graphics, synthesis, and diastereomeric complex formation in aqueous solution

• Published in: Journal of the American Chemical Society Vol. 110; no. 6; pp. 1679 - 1690
• Main Authors: Dharanipragada, Ramalinga, Ferguson, Stephen B, Diederich, Francois
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.03.1988
• Subjects: Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Organic chemistry; Preparations and properties; Enantiomer(+); Ion pair; Polycyclic compound; Chiral compound; Condensed benzenic compound; Spiran; Macrocycle; Quaternary ammonium compound; Intercalation compound; Carboxylate; Cyclophane; Aqueous solution; NMR spectrum; Organic dication; Oxygen nitrogen heterocycle
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja00214a004

The application of molecular mechanics (MM2) to the design of the novel optically active macrocyclic host (+)-10 is described. The cavity binding site of host (+)-10 is shaped by both a diphenylmethane and a 4-phenyl-1,2,3,4-tetrahydroisoquinoline unit bridged by two 1,4-dioxabutane chains. Two quaternary ammonium ions located remote of the apolar cavity binding site provide water solubility to the macrocycle. The observation that the complexes of the methyl esters (R,S)-29 are more stable than the complexes of naproxen (R,S)-28 leads to the conclusion that ion pairing between the carboxylate of the guest and the quaternary tetrahydroisoquinolinium nitrogen of the host is not effective as a binding and discriminating interaction in the diastereomeric complexes of (R,S)-naproxen. Molecular mechanics (MM2) in combination with computer graphics (HYDRA) are applied to the analysis of the geometries of free host and of host-guest complexes.