Qiu Wei-Qing, Cui Yong-Mei, Tang Ping, Qiu Yuan-You, Lin Hai-Xia
a Department of Chemistry, Innovative Drug Research Center, College of Sciences , Shanghai University , Shanghai , China.
Nat Prod Res. 2018 Jan;32(2):121-127. doi: 10.1080/14786419.2017.1340281. Epub 2017 Jun 28.
Three novel nor-seco-taxoids 13, 15, 23 in which the A rings are cleaved but the B, C, and D rings are retained were prepared from 1-deoxybaccatin VI via its nor-dioxo derivative and their structures were confirmed by H NMR, C NMR and high resolution MS. Oxidative introduction of C-1 hydroxyl to 1-deoxybaccatin VI with oxidising agent KBrO and catalyst RuCl led to the dioxo derivative 6 and its structure is determined by X-ray crystallographic analysis. A-seco taxoids 13, 15, 23 with a C-13 ester linkage were tested for cytotoxic activity and all compounds showed no measurable cytotoxic activity against HCT-116 cell line. However, 1-deoxy-9a-dihydrotaxane analogue 4 semi-synthesised from 1-deoxybaccatin VI is 10-fold less cytotoxic than paclitaxel, indicating the indispensible nature of the A ring double bond for the bioactivity of paclitaxel.
通过1-脱氧巴卡亭VI的去氧二氧代衍生物制备了三种新型去甲紫杉烷类化合物13、15、23，其中A环被裂解，但B、C和D环保留，其结构通过氢核磁共振（H NMR）、碳核磁共振（C NMR）和高分辨率质谱（HRMS）得以确证。用氧化剂溴酸钾（KBrO）和催化剂RuCl将1-脱氧巴卡亭VI的C-1羟基进行氧化引入，得到二氧代衍生物6，其结构通过X射线晶体学分析确定。对具有C-13酯键的A-裂环紫杉烷类化合物13、15、23进行了细胞毒性活性测试，所有化合物对HCT-116细胞系均未显示出可测量的细胞毒性活性。然而，由1-脱氧巴卡亭VI半合成的1-脱氧-9a-二氢紫杉烷类似物4的细胞毒性比紫杉醇低10倍，这表明A环双键对于紫杉醇的生物活性具有不可或缺的性质。
