Khdar Zein Alabdeen, Le Tam Minh, Schelz Zsuzsanna, Zupkó István, Szakonyi Zsolt
Institute of Pharmaceutical Chemistry, Interdisciplinary Excellent Center, University of Szeged Eötvös utca 6 H-6720 Szeged Hungary
HUN-REN-SZTE Stereochemistry Research Group, University of Szeged H-6720 Szeged Eötvös utca 6 Hungary.
RSC Adv. 2024 Nov 18;14(49):36698-36712. doi: 10.1039/d4ra07334g. eCollection 2024 Nov 11.
A new series of aminodiols, aminotetraols and 1,2,3-triazoles based on -gibberic acid were synthesized in a stereoselective manner, starting from commercially available gibberellic acid. -Gibberic acid, prepared from gibberellic acid according to a literature method, was applied to SeO/-BuOOH-mediated allylic oxidation, yielding the triol, which is a key intermediate. After protecting the 1,4-diol functionality as acetonide, epoxidation was performed using either -CPBA or -BuOOH/VO(acac) to produce the epoxy alcohol. Then, the oxirane ring was opened with either primary amines to provide aminodiols or sodium azide to afford azido diols. The latter was subjected to the CuAAC reaction to obtain dihydroxy 1,2,3-triazoles. HCl-mediated acetonide deprotection of the prepared derivatives furnished aminotetraols and tetrahydroxy 1,2,3-triazoles. The antiproliferative effects of the prepared compounds were studied by the MTT method against a panel of human cancer cell lines (HeLa, SiHa, A2780, MCF-7 and MDA-MB-231) and fibroblasts, and the structure-activity relationships for the prepared compounds were explored.
以市售赤霉素为起始原料，以立体选择性方式合成了一系列基于赤霉酸的新型氨基二醇、氨基四醇和1,2,3 -三唑。根据文献方法由赤霉素制备的赤霉酸用于二氧化硒/叔丁基过氧化氢介导的烯丙基氧化反应，生成三醇，该三醇是关键中间体。在将1,4 -二醇官能团保护为丙酮叉后，使用间氯过氧苯甲酸或叔丁基过氧化氢/乙酰丙酮氧钒进行环氧化反应生成环氧醇。然后，环氧乙烷环用伯胺开环得到氨基二醇，或用叠氮化钠开环得到叠氮二醇。后者进行铜催化的叠氮化物-炔环加成反应得到二羟基1,2,3 -三唑。通过盐酸介导对所制备衍生物的丙酮叉脱保护得到氨基四醇和四羟基1,2,3 -三唑。采用MTT法研究了所制备化合物对一组人癌细胞系（HeLa、SiHa、A2780、MCF - 7和MDA - MB - 231）和成纤维细胞的抗增殖作用，并探讨了所制备化合物的构效关系。
