Synthesis and complexation properties of a water-soluble optically active cyclophane incorporating a 4-naphthyl-1,2,3,4-tetrahydroisoquinoline unit as a chiral spacer

Abstract

The unnatural alkaloid 6-methoxy-4-[2-(6-methoxynaphthalenyl)]-1,2,3,4-tetrahydroisoquinoline (5) was prepared as a chiral spacer for optically active cyclophane receptors. Optical resolution of the building block was accomplished through diastereomeric salt formation with dibenzoytartaric acid. The S configuration was assigned by X-ray crystallographic methods to the hydrochloride salt of (−)-5. Starting from enantiomerically pure 5, the optically active cyclophanes (R)- (S)-4 were prepared. These cyclophanes, in which the chiral alkaloid spacer is bridged to an chiral diphenylmethane unit, are efficient binders of naphthalene derivatives in D 2 O/CD 3 OD (60:40, v/v and show a modest degree of chiral recognition in the inclusion complexation of naproxen derivatives