Secretary For Anti-aids Drugs Telbivudine And Ritonavir Chiral Intermediates Synthesis

Stavudine and Ritonavir are effective therapeutic agents for the treatmentof AIDS. The present thesis relates to the sylltheses of Stavudine and the chiralintermediate of Ritonavir referring to reported synthetic routes and somemodification in preparative techniques to be suitable for potelltial productionin industrial scale.Stavudine is a 2', 3'-dideoxy-2', 3'-didehydro nucleoside analog withreverse transcriptase inhibitive activity The synthesis of Stavudine comprisesthe following steps: Mesylation of 5-methyluridine gives trimesylated5-methyluridine. Mesylated 5-methyluridine reacted with sodium benzoate inacetylamine is converted to 5'-benzoated-2, 2' - anhydro - 5' -methyluridine,which is brominated to give 5' -benzoyl -2' -bromo - 3' -mesylthymidine.Zinc-induced reductive elimination provides 5'-benzoyl ester of Stavudine.Deprotection of Stavudine ester affbrds final product in total yied 42.5%.Ritonavir is a protease inhibitor with a chaintyped strucfore of peptidecompound. The key intermediate of kitonavir is a chiral amino alcohol with 3chiral carbons. Preparation of the chiral amino alcohol starts from(L)-phenylalanine. Esteriflcation of phenylalbone followed by nucleophilicsubstitution with acetonitrile anion and reaction with Grignard reagentprovides an enaminone intermediate. Through enanioselective reduction ofthe enaxninone in two steps, the key chiral intermediate of Ritonavir is formedin 21 .7% yield.