Synthesis, reactions and conformational analysis of 5-arylidene-2-thiohydantoins as potential antiviral agents

(Z)-5-Arylidene-1-(4-methylphenylsulfonyl)-2-thiohydantoins 5a,b were synth esized from the direct condensation of the aromatic aldehydes 4a,b with 1-( 4-methylphenylsulfonyl)-2-thiohydantoins 3a,b. Compounds 5a,b were coupled with 2'-deoxy-3',5'-di(4-methylbenzoyl)-alpha -D-erythro-pentofuranosyl chl oride 6 under alkaline conditions to afford N-3-protected nucleosides 7a,b. Reaction of 5a,b with chloromethyl methyl sulfide and/or 2-bromoacetaldehy de diethyl acetal in alkaline medium afforded N-3-alkyl derivatives 8a-c. R eaction of 5a with 1,2-dichloroethane in alkaline conditions afforded bis-t hiohydantoinylethane 9a,b. Compounds 5a,b were condensed with formaldehyde and secondary amines to afford 3-aminomethyl-2-thiohydantoins derivatives 1 0a-d. On the other hand, reaction of unsubstituted 2-thiohydantoins derivat ives 11b,c with chloromethyl methyl sulfide afforded the mono- and bis-meth ylthio derivatives 12a,b and 13a,b, respectively. Reaction of 11b,c with se condary amines and formaldehyde gave 3-aminomethyl-2-thiohydantoins 14a-e. Reaction of 11a-c with bromoacetaldehyde diethyl acetal yielded the S-alkyl derivatives 15a-c which can be hydrolysed with ethanolic hydrochloric acid to afford 5-arylidenehydantoins 16a-c. The compounds do not display any an tiviral activity.