Eur. J. Med. Chem., 39, 37-48, (2004)


Tetrahydroacridin-9-ones, 9-chlorotetrahydroacridines, 9-amino- tetrahydroacridines and 9-(pyrazol-1-yl)-tetrahydroacridinines derived from chiral cyclanones

A series of tetrahydroacridines related to tacrine have been synthesized starting from 3-methylcyclohexananone, menthone, pulegone, carvone and dihydrocarvone (both racemic and chiral). In many cases, the yields and purity of the compounds have been improved by the use of a microwave oven. These compounds have been characterized by (1)H and (13)C NMR data. To establish their relative configuration, the structure of (1R,4R)-(+)-9-chloro-1-methyl-4-isopropyl-1,2,3,4-tetrahydroacridine (cis-10b), derived from (2S,5R)-(-)-menthone, has been determined by X-ray. The chemical shifts of cis-10b and trans-10b have been calculated at the GIAO/B3LYP/6-31G* level and compared successfully with the experimental data.