Amino-9-deoxydaunomycin and related compounds, in which the hydroxyl group at the 9-position of daunomycin is replaced by an amino group, have been synthesized. Asymmetry was introduced into the synthetic sequence for the AB synthon by resolution of the intermediate amino ester or acetamido acid to afford (/?)-(-)-2-acetyl-2-acetamido-5,8-dimethoxy-l,2,3,4-tetrahydronaphthalene, which was converted to the tetracyclic amido ketones by Friedel-Crafts acylation with phthalic anhydride or its 3-methoxy derivative. The resulting regioisomers 4-and 1-methoxy compounds were separated, after methylation and selective demethylation, by crystallization and preparative TLC. The required introduction of the C7-hydroxyl function proceeded stereospecifically via a three-step reaction sequence involving formation of an oxazine compound. The silver trifluoromethane assisted glycosidation of the resulting aglycons with 2-deoxy-3,4-di-0-acetyl-D-eryi/iro-pentopyranosyl bromide or jV,0-bis(trifluoroacetyl)daunosaminyl chloride, followed by alkaline hydrolysis afforded the target glycosides. The work reported herein comprises an eff and its analogues with the same stereochemistry as i:

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A series of cyclic imides bearing a omega-(4-aryl and 4-heteroaryl-1-piperazinyl)alkyl moieties was synthesized and tested in vivo for anxiolytic activity. The in vitro binding affinities of these compounds were also examined for 5-HT1A receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, (1R*,2S*,-3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3- bicyclo[2.2.1]heptanedicarboximide (1: tandospirone), was found to be equipotent with buspirone in its anxiolytic activity and more anxio-selective than buspirone and diazepam. Tandospirone (1) is currently undergoing clinical evaluation as a selective anxiolytic agent.

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