A Practical and Azide-Free Synthetic Approach to Oseltamivir from Diethyl d-Tartrate

• Published in: Journal of organic chemistry Vol. 75; no. 9; pp. 3125 - 3128
• Main Authors: Weng, Jiang, Li, Yong-Bo, Wang, Rui-Bin, Li, Feng-Quan, Liu, Can, Chan, Albert S. C, Lu, Gui
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 07.05.2010; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Animals; Antiviral Agents - chemical synthesis; Chemistry; Chemistry, Organic; Cyclization; Cyclohexenes - chemistry; Enzyme Inhibitors - chemical synthesis; Exact sciences and technology; Humans; Influenza A Virus, H5N1 Subtype - enzymology; Molecular Structure; Neuraminidase - antagonists & inhibitors; Organic chemistry; Oseltamivir - chemical synthesis; Physical Sciences; Preparations and properties; Science & Technology; Tartrates - chemistry; ESTER; DESIGN; NEURAMINIDASE INHIBITORS; ASYMMETRIC-SYNTHESIS; TAMIFLU; THERAPY; INFLUENZA; Michael addition; Azides; Nitro compound; Oseltamivir; Asymmetric synthesis; Organic azide; Nitrogen heterocycle; Horner Emmons reaction; Chemical synthesis; Aldol condensation; Successive reaction; Henry reaction
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo100187m

A short and practical synthesis of oseltamivir was accomplished in 11 steps from inexpensive and abundant diethyl d-tartrate starting material. This azide-free route featured an asymmetric aza-Henry reaction and a domino nitro-Michael/Horner−Wadsworth−Emmons (HWE) reaction as the key steps to construct the relevant cyclohexene ring of the product, which provided an economical and practical alternative for the synthesis of oseltamivir.