Xu Leichuan, Ma Haoyun, An Xinkun, Li Yihao, Zhang Qian, Liu Xinlei, Wang Mingan
Department of Applied Chemistry, College of Science, China Agricultural University Beijing 100193 People's Republic of China
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。
