Total synthesis, structure revision and cytotoxic activity of Sch 53825 and its derivatives

The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield through N-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps. On this basis, the synthesis of palmarumycin B-6 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-1, C-13 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 IC50 < 0.5 mu M.

Automated summary

The first total synthesis of Sch 53825 was accomplished in 12 steps, yielding a final product. Using the same starting material, palmarumycin B-6 was synthesized in 6 steps. Additionally, three new analogues with two chlorine atoms were synthesized. The structure of natural Sch 53825 was revised based on its characterization. Compound 11 exhibited excellent cytotoxicity against several tumor cell lines.