Lee C B, Chou T C, Zhang X G, Wang Z G, Kuduk S D, Chappell M D, Stachel S J, Danishefsky S J
The Laboratory for Bioorganic Chemistry, The Sloan-Kettering Institute for Cancer Research, New York, New York 10021, USA.
J Org Chem. 2000 Oct 6;65(20):6525-33. doi: 10.1021/jo000617z.
A new epothilone analogue, 12,13-desoxyepothilone F (dEpoF, 21-hydroxy-12,13-desoxyepothilone B, 21-hydroxyepothilone D), was synthesized and evaluated for antitumor potential. A convergent strategy employed for the semipractical synthesis of 12,13-desoxyepothilone B (dEpoB) has been utilized to yield an amount of dEpoF sufficient for relevant biological studies. The results from an in vitro assay reveal that this new analogue is highly active against various tumor cell lines with a potency comparable to that of dEpoB. In particular, the growth of resistant tumor cells is inhibited by dEpoF at concentrations where paclitaxel (Taxol) is basically ineffective. A preliminary assessment of its in vivo activity is also promising. The new analogue, containing an additional hydroxyl group at C21, exhibits advantages over other epothilones in terms of water solubility, and can serve as a readily functionalizable handle to produce other useful compounds for pertinent biological studies.
合成了一种新的埃坡霉素类似物，12,13-脱氧埃坡霉素F（dEpoF，21-羟基-12,13-脱氧埃坡霉素B，21-羟基埃坡霉素D），并对其抗肿瘤潜力进行了评估。用于半实用合成12,13-脱氧埃坡霉素B（dEpoB）的汇聚策略已被用于产生足以进行相关生物学研究的dEpoF量。体外试验结果表明，这种新类似物对各种肿瘤细胞系具有高活性，其效力与dEpoB相当。特别是，在紫杉醇（泰素）基本无效的浓度下，dEpoF可抑制耐药肿瘤细胞的生长。对其体内活性的初步评估也很有前景。这种新类似物在C21位含有一个额外的羟基，在水溶性方面比其他埃坡霉素具有优势，并且可以作为一个易于官能化的基团来制备用于相关生物学研究的其他有用化合物。
