Review of the Patent and Journal Literature: Synthesis and Final Forms of Antifungal Prodrug Isavuconazonium Sulfate

This review provides a comprehensive summary of the synthesis of the second-generation antifungal agent isavuconazole, its water-soluble prodrug, isavuconazonium, and the prodrug side chain. Establishing contiguous stereocenters and forming the thiazole ring pose the most significant challenges in the synthesis of isavuconazole. Current approaches have faced difficulties in balancing effectiveness and scalability. Additionally, the instability of isavuconazonium, incomplete salt form transformation, and requirement for lyophilization greatly limit the large-scale production of isavuconazonium sulfate. Through this review, we hope to inspire future developments that could potentially address these issues.