Sch 53825及其衍生物的全合成、结构修正与细胞毒性活性
Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives.
作者信息
Xu Leichuan, Ma Haoyun, An Xinkun, Li Yihao, Zhang Qian, Liu Xinlei, Wang Mingan
机构信息
Department of Applied Chemistry, College of Science, China Agricultural University Beijing 100193 People's Republic of China
出版信息
RSC Adv. 2022 Jun 14;12(27):17629-17636. doi: 10.1039/d2ra02898k. eCollection 2022 Jun 7.
The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through -benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps. On this basis, the synthesis of palmarumycin B was improved using the same raw material with 6 steps and 32% overall yield. Also, three new analogues with two chlorine atoms were synthesized. Their structures were characterized by H, C NMR, HR-ESI-MS and X-ray diffraction data. The structure of natural Sch 53825 was revised as an epimer of compound 1 with the anti-hydroxy epoxide at C-4. Their cytotoxic activities against several tumor cell lines (HCT116, U251, BGC823, Huh-7 and PC9) showed that compound 11 exhibited excellent cytotoxicity against above mentioned cancer cell lines with IC < 0.5 μM.
以5-羟基-1-四氢萘酮为原料，通过苄基氯化辛可宁催化的不对称环氧化反应和Mitsunobu反应作为关键步骤，经12步反应首次全合成了Sch 53825（14），总收率为16%。在此基础上，以相同原料对棕榈霉素B的合成进行了改进，经6步反应，总收率为32%。此外，还合成了三种含两个氯原子的新类似物。通过氢谱、碳谱、高分辨电喷雾电离质谱和X射线衍射数据对其结构进行了表征。天然Sch 53825的结构被修订为化合物1的差向异构体，其C-4位具有反式羟基环氧化物。它们对几种肿瘤细胞系（HCT116、U251、BGC823、Huh-7和PC9）的细胞毒性活性表明，化合物11对上述癌细胞系表现出优异的细胞毒性，IC<0.5μM。
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