Abstract Five new and three known longipinane derivatives were obtained and their molecular interactions with α,β-tubulin were evaluated using in vitro and in silico assays. Alkaline hydrolysis of the natural longipinane diester 3, isolated in high yields from the roots of Stevia serrata, gave (3R,4S,5S,7S,8R,9S,10R,11R)-longipinan-7,8,9-triol-1-one (1). Compounds 1 and 3 were the starting materials for the preparation of esters 2, 4–8 derived from acetic, angelic, benzoic, cinnamic, and 4-fluorocinnamic acids. It was found that the presence of cinnamate groups on the longipinane framework of 5–8 accelerated tubulin polymerization, while (3R,4S,5S,7S,8S,9S,10R,11R)-7,8-dicinnamoyloxy-9-hydroxylongipinan-1-one (5) also induced significant microtubule stabilization. Molecular docking studies revealed that 5 (Edock = −9.88 kcal/mol) interacts at the paclitaxel binding site of tubulin, suggesting that this could be the mechanism for producing microtubule stability, while saturation-transfer difference NMR spectroscopy experimentally confirmed that 5 binds to tubulin.

中文翻译：

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作为新型微管稳定剂的 longipinane 衍生物的合成、分子对接和饱和转移差异核磁共振波谱

摘要 获得了五种新的和三种已知的 longipinane 衍生物，并使用体外和计算机试验评估了它们与 α,β-微管蛋白的分子相互作用。从甜叶菊根部以高产率分离的天然 longipinane 二酯 3 的碱水解得到 (3R,4S,5S,7S,8R,9S,10R,11R)-longipinan-7,8,9-triol-1 -一（1）。化合物 1 和 3 是制备由乙酸、当归酸、苯甲酸、肉桂酸和 4-氟肉桂酸衍生的酯 2、4-8 的起始材料。发现5-8的longipinane骨架上肉桂酸酯基团的存在加速了微管蛋白聚合，而(3R,4S,5S,7S,8S,9S,10R,11R)-7,8-dicinnamoyloxy-9-hydroxylongipinan- 1-一 (5) 还诱导显着的微管稳定。分子对接研究表明 5 (Edock = -9.