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Synthesis of the 1,5-Diazabicyclo[6.3.0]dodecane Core Structure of Xevinapant
Bohao Wang1, Shen Zhai1, Yingzhi Ren2
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
Abstract:
Inhibitors of apoptosis proteins (IAPs) are key targets in cancer therapy due to their role in promoting cancer cell survival. The second mitochondria-derived activator of caspases (SMAC) mimetics, which antagonize IAPs, have shown therapeutic potential for cancers. 1,5-Diazabicyclo[6.3.0]dodecanone amino acid scaffold serves as an important scaffold for developing SMAC mimetics, including clinical candidates like Xevinapant and Dasminapant. Herein, we report a novel, efficient, and potentially scalable synthesis of the core structure of Xevinapant achieved in 7 steps from a pyroglutamic acid derivative, with an overall yield of 8.4%, facilitating further development of IAP inhibitors.
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