title: Organocatalytic and scalable synthesis of the anti-influenza drugs zanamivir, laninamivir, and CS-8958.
abstract: Zanamivir, laninamivir, and CS-8958 are three neuraminidase inhibitors that have been clinically used to combat influenza. We report herein a novel organocatalytic route for preparing these agents. Only 13 steps are needed for the assembly of zanamivir and laninamivir from inexpensive D-araboascorbic acid by this synthetic route, which relies heavily on a thiourea-catalyzed enantioselective Michael addition of acetone to tert-butyl (2-nitrovinyl)carbamate and an anti-selective Henry reaction of the resulting Michael adduct with an aldehyde prepared from D-araboascorbic acid. The synthetic procedures are scalable, as evident from the preparation of more than 3.5 g of zanamivir.
authors.affiliation: State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032 (China).
authors.forename: Junshan
authors.initials: J
authors.lastname: Tian
authors.forename: Jiankang
authors.initials: J
authors.lastname: Zhong
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Li
authors.forename: Dawei
authors.initials: D
authors.lastname: Ma
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D002384:Catalysis; D006146:Guanidines; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy; D011714:Pyrans; D012794:Sialic Acids; D053243:Zanamivir / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; C546919:CS 8958; D006146:Guanidines; D011714:Pyrans; D012794:Sialic Acids; C546918:laninamivir; D053243:Zanamivir
keywords: anti-influenza drugs; asymmetric catalysis; organocatalysis; scalable synthesis; total synthesis