Division of Applied Biological and Rare Sugar Sciences, Graduate School of Agriculture, Kagawa University, Kagawa 761-0795, Japan.
Department of Applied Biological Science, Faculty of Agriculture, Kagawa University, Kagawa 761-0795, Japan.
Bioorg Med Chem. 2022 Nov 1;73:116988. doi: 10.1016/j.bmc.2022.116988. Epub 2022 Aug 27.
A simplified analog (3) of aplysiatoxin was synthesized. Compound 3 has only one tetrahydropyran ring at positions 3-7, the A-ring of the spiroketal moiety, which is the conformation-controlling unit for the macrolactone ring. Nuclear magnetic resonance (NMR) analysis and density functional theory (DFT) calculations indicated that 3 existed as an equilibrium mixture of two conformers arising from inversion of the chair conformation of the 2,6-trans-tetrahydropyran ring. The des-B-ring analog 3 binds protein kinase C isozymes and exhibits antiproliferative activity toward human cancer cell lines, comparable to 18-deoxy-aplog-1 with a spiroketal moiety.
阿普里西毒素的简化类似物 (3) 被合成。化合物 3 在位置 3-7 处只有一个四氢吡喃环，即螺缩酮部分的 A 环，这是大环内酯环的构象控制单元。核磁共振 (NMR) 分析和密度泛函理论 (DFT) 计算表明，3 以两种构象的平衡混合物形式存在，这是由于 2,6-反式四氢吡喃环的椅式构象的反转引起的。去 B-环类似物 3 与蛋白激酶 C 同工酶结合，并表现出对人癌细胞系的抗增殖活性，与具有螺缩酮部分的 18-去氧-aplog-1 相当。
