Synthesis of (−)-Oseltamivir Phosphate (Tamiflu) Starting from cis-2,3-Bis(hydroxymethyl)aziridine

• Published in: Journal of organic chemistry Vol. 77; no. 19; pp. 8792 - 8796
• Main Authors: Oh, Hong-Se, Kang, Han-Young
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 05.10.2012; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Alkylation; Aziridines - chemistry; Catalysis; Chemistry; Chemistry, Organic; Cyclization; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Molecular Structure; Organic chemistry; Organometalloidal and organometallic compounds; Oseltamivir - chemical synthesis; Oseltamivir - chemistry; P derivatives; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; HIGH-YIELDING SYNTHESIS; OSELTAMIVIR TAMIFLU; ASYMMETRIC-SYNTHESIS; NEURAMINIDASE INHIBITORS; INHIBITOR (-)-OSELTAMIVIR; AZIRIDINES; EFFICIENT; ACCESS; DESYMMETRIZATION; Nitrogen heterocycle; Cyclohexene derivative; Metathesis; Desymmetrization; Chiral compound; Aziridine derivatives; Phosphorus Organic compounds; Allylation; Oseltamivir; Cyclization; Cyclic compound; Organic phosphate; Chemical synthesis; Protection
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo3015853

Oseltamivir phosphate (Tamiflu) has been synthesized from cis-2,3-bis(hydroxymethyl)aziridine. After protection of the cis-2,3-bis(hydroxymethyl)aziridine with a Boc group, desymmetrization provided a chiral aziridine, which was a key intermediate to install the required stereogenic center containing a nitrogen atom. Allylation and ring closing metathesis are the key reactions to obtain the cyclic product that was successfully converted to the desired oseltamivir phosphate.