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磷酸奥司他韦绿色合成研究进展
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Abstract:
流感是一种严重的呼吸道疾病，其治疗主要依赖神经氨酸酶抑制剂。1999年获批的磷酸奥司他韦(商品名：达菲)是目前最有效的口服抗流感神经氨酸酶抑制剂之一。然而，传统的达菲合成工艺存在两大关键缺陷，一是需要使用叠氮化合物，叠氮化合物容易发生爆炸，在工业规模合成中存在显著安全隐患；二是达菲合成的起始原料莽草酸是一种天然产物，主要来源是中国植物八角，其供应稳定性难以满足工业化生产需求。迄今已发展出70余种合成路线。本文系统综述了其中具有代表性的绿色合成路径，为未来的工业合成优化提供方向。
Influenza is a severe respiratory disease whose treatment requires neuraminidase inhibitors. Oseltamivir phosphate (Tamiflu), approved in 1999, is one of the most effective oral anti-influenza neuraminidase inhibitors. The traditional synthesis of Tamiflu suffers from two major drawbacks: first, the use of explosive azide compounds, which poses significant safety hazards in industrial-scale synthesis; second, reliance on shikimic acid as the starting material. As a natural product mainly derived from Chinese star anise, shikimic acid faces challenges in stable supply for industrial production. Consequently, over 70 synthetic routes have been developed to date. This article reviews representative optimized synthetic approaches that address these limitations, providing insights for future industrial process optimization toward greener and more efficient production.
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