Department of Chemistry, Hunter College and The Graduate Center of the City University of New York, New York, NY, 10065, USA.
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Carbohydr Res. 2022 Nov;521:108671. doi: 10.1016/j.carres.2022.108671. Epub 2022 Sep 7.
The THF containing acetogenin 4-deoxyannonmontacin (4-DAN) has attracted interest for its potent cytotoxicity against a broad range of human tumor cell lines, and relatively simple structure. Herein is described the synthesis and cytotoxicity of C-10 epimers of 4-DAN and analogues thereof comprising carbohydrate and thiophene substitutes for the THF and butenolide moieties respectively. The key synthetic ploy was the union of THF and butenolide segments or their substitutes, via an alkene cross metathesis. The different analogues showed cytotoxicity in the low micromolar to nanomolar range against the human prostate cancer cell lines LNCaP and PC3. A relatively simple mannose-linked thiophene analog was found to be similar in activity to 4-DAN.
含有乙酰氧基醇 4-去甲annonmontacin（4-DAN）的四氢呋喃引起了人们的兴趣，因为它对广泛的人类肿瘤细胞系具有强大的细胞毒性，而且结构相对简单。本文描述了 4-DAN 的 C-10 差向异构体及其类似物的合成和细胞毒性，其中包括分别替代 THF 和丁烯内酯部分的碳水化合物和噻吩取代物。关键的合成策略是通过烯烃交叉复分解将 THF 和丁烯内酯片段或其取代物连接起来。不同的类似物对人前列腺癌细胞系 LNCaP 和 PC3 表现出低微摩尔至纳摩尔范围内的细胞毒性。发现相对简单的甘露糖连接的噻吩类似物与 4-DAN 具有相似的活性。
