SYNTHESIS, REACTIONS AND CONFORMATIONAL ANALYSIS OF 5-ARYLIDENE-2-THIOHYDANTOINS AS POTENTIAL ANTIVIRAL AGENTS

Abstract(Z)-5-Arylidene-1-(4-methylphenylsulfonyl)-2-thiohydantoins 5a,bwere synthesized from the direct condensation of the aromatic aldehydes 4a,bwith 1-(4-methylphenylsulfonyl)-2-thiohydantoins 3a,b. Compounds 5a,bwere coupled with 2′-deoxy-3′,5′-di(4-methyl-benzoyl)-α-D-erythro-pentofuranosyl chloride 6under alkaline conditions to afford N3-protected nucleosides 7a,b. Reaction of 5a,bwith chloromethyl methyl sulfide and/or 2-bromoacetaldehyde diethyl acetal in alkaline medium afforded N3-alkyl derivatives 8a-c. Reaction of 5awith 1,2-dichloroethane in alkaline conditions afforded bis-thiohydantoinylethane 9a,b. Compounds 5a,bwere condensed with formaldehyde and secondary amines to afford 3-aminomethyl-2-thiohydantoins derivatives 10a-d. On the other hand, reaction of unsubstituted 2-thiohydantoins derivatives 11b,cwith chloromethyl methyl sulfide afforded the mono- and bis-methylthio derivatives 12a,band 13a,b, respectively. Reaction of 11b,cwith secondary amines and formaldehyde gave 3-aminomethyl-2-thiohydantoins 14a-e. Reaction of 11a-cwith bromoacetaldehyde diethyl acetal yielded the S-alkyl derivatives 15a-cwhich can be hydrolysed with ethanolic hydrochloric acid to afford 5-arylidenehydantoins 16a-c. The compounds do not display any antiviral activity.