A practical synthetic route for pilot production of entecavir is described. It is safe, robust, and scalable to kilogram scale. Starting from (S)-(+)-carvone, this synthetic route consists of a series of highly efficient reactions including a Favorskii rearrangement-elimination-epimerization sequence to establish the cyclopentene skeleton, the Baeyer–Villiger oxidation/rearrangement to afford the correct configuration of the secondary alcohol, and a directed homoallylic epoxidation followed by epoxide ring-opening to introduce the hydroxyl group suitable for the Mitsunobu reaction. In addition, the synthesis contains only four brief chromatographic purifications.

中文翻译：

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恩替卡韦的全合成：中试生产的可靠途径

描述了用于恩替卡韦中试生产的实用合成途径。它是安全，可靠且可扩展至公斤级的。从（S）-（+）-香芹酮开始，该合成路线由一系列高效反应组成，包括Favorskii重排-消除-上位化序列以建立环戊烯骨架，Baeyer-Villiger氧化/重排以提供正确的构型然后，进行仲醇的直接芳族环氧化，然后进行环氧化物开环，以引入适合于Mitsunobu反应的羟基。此外，该合成仅包含四个简短的色谱纯化。