Synthesis of Anti-Pancreatic Cancer Natural Product Majusculamide D and Analogues Reveals a Preliminary Structure-Activity Relationships
Xiuhe Zhao
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350 China
Search for more papers by this authorMengxue Lv
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350 China
Search for more papers by this authorXiaonan Xi
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350 China
Search for more papers by this authorYaxin Lu
College of Chemistry, Nankai University, Tianjin, 300071 China
Search for more papers by this authorCorresponding Author
Liang Wang
College of Chemistry, Nankai University, Tianjin, 300071 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Yue Chen
College of Chemistry, Nankai University, Tianjin, 300071 China
E-mail: [email protected]; [email protected]Search for more papers by this authorXiuhe Zhao
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350 China
Search for more papers by this authorMengxue Lv
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350 China
Search for more papers by this authorXiaonan Xi
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, Nankai University, Tianjin, 300350 China
Search for more papers by this authorYaxin Lu
College of Chemistry, Nankai University, Tianjin, 300071 China
Search for more papers by this authorCorresponding Author
Liang Wang
College of Chemistry, Nankai University, Tianjin, 300071 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Yue Chen
College of Chemistry, Nankai University, Tianjin, 300071 China
E-mail: [email protected]; [email protected]Search for more papers by this authorComprehensive Summary
The total synthesis of majusculamide D (1) was achieved from commercially available materials. In addition, we synthesized eight analogues including three stereoisomers of majusculamide D that differ in the fatty acid chain. Six analogues including a simplified analogue 29 exhibited significant nanomolar-level IC50 values against Panc-1 cells in MTT assays. A preliminary SAR analysis indicated that the hydroxyl group at C10 and C2−C3 unsaturated double bond of majusculamide D were essential in maintaining the high activity against Panc-1 cells and the orientation of C40-Me and C42-Me groups was tolerable.
Supporting Information
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