Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6834-7. doi: 10.1016/j.bmcl.2013.10.007. Epub 2013 Oct 11.
By-product 9a exhibited potent cytotoxicity against both SK-OV-3 and A549 cell lines. The structure of 9a was characterized using 1D and 2D NMR experiments and confirmed by synthesis to afford a diastereomeric mixture (16a) that was identical to 9a, as well as a pair of diastereomers (R)-16b and (S)-16c. The preliminary SAR study demonstrated that analogs with an (R)-configuration were slightly more potent than analogs with an (S)-configuration. In addition, α,α-gem-dimethyl analogs 16 g-i were the most potent analogs in this series, exhibiting similar potency to docetaxel and greater potency than Taxol against the SK-OV-3 cell line. For the A549 cell line, analogs 16 g-i were more potent (>65-fold) than both docetaxel and Taxol.
副产物 9a 对 SK-OV-3 和 A549 细胞系均表现出很强的细胞毒性。通过 1D 和 2D NMR 实验对 9a 的结构进行了表征，并通过合成进行了确认，得到了非对映异构体混合物（16a），其与 9a 完全相同，以及一对非对映异构体（R）-16b 和（S）-16c。初步 SAR 研究表明，具有（R）构型的类似物比具有（S）构型的类似物略强。此外，α，α-双甲基类似物 16g-i 是该系列中最有效的类似物，其对 SK-OV-3 细胞系的活性与多西紫杉醇相当，比紫杉醇的活性更强。对于 A549 细胞系，类似物 16g-i 的活性比多西紫杉醇和紫杉醇都要强（>65 倍）。
