Recent Progress in the Synthesis of Entecavir

Entecavir, as the most effective hepatitis B virus (HBV) DNA polymerase inhibitor currently used in the clinical treatment of chronic hepatitis B, holds significant clinical value. This paper systematically reviews the latest research advances (2012–2025) in the total synthesis of entecavir. Based on the differences in synthetic strategies for constructing its core cyclopentane skeleton, existing synthetic routes are categorized into three types: Carbon ring construction strategies mediated by cycloaddition and ring‐closing metathesis, multi‐catalytic cascade and fully catalytic asymmetric synthesis strategies, and stereoselective epoxide transformation and tandem reaction strategies. This classification not only clearly presents the technical characteristics of different synthetic approaches but also provides an important reference for the development of carbocyclic nucleoside analogs.