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This Focus Review summarizes recent advances in the synthesis of betulinic acid derivatives with modified A‐rings. It also focuses on their application as potential therapeutic agents for the treatment of cancer and other diseases. Betulinic acid (BA) exhibits therapeutically interesting biological properties, including antitumor, anti‐HIV, antiprotozoal, and hepato‐ or nephroprotective activity; however, its clinical use has been severely limited by its higher IC50 value and worse pharmacological parameters than the currently used drugs. On the other hand, semisynthetic analogues of BA are much better suited for potential clinical use. Among these analogues, compounds that contain a modified A‐ring are the most promising. We hope that this Focus Review will serve as a guide for the synthesis of new BA derivatives with applications as drug candidates. A general audience may also find this Focus Review interesting, because it describes the structural motifs that are responsible for the observed bioactivities.

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