Organocatalytic and Scalable Synthesis of the Anti‐Influenza Drugs Zanamivir,Laninamivir, and CS‐8958 |
| |
Authors: | Yunsheng Li Prof?Dr Dawei Ma |
| |
Institution: | State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032 (China) |
| |
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. |
| |
Keywords: | anti‐influenza drugs asymmetric catalysis organocatalysis scalable synthesis total synthesis |
|
|