D'yakonov Vladimir A, Islamov Ilgiz I, Dzhemileva Lilya U, Makarova Elina Kh, Dzhemilev Usein M
Institute of Petrochemistry and Catalysis, Russian Academy of Sciences, Pr. Oktyabrya 141, 450075 Ufa, Russia.
Int J Mol Sci. 2021 Aug 16;22(16):8787. doi: 10.3390/ijms22168787.
An original synthetic route was developed for the preparation of previously unknown unsaturated polyaromatic macrolactones containing a 1Z,5Z-diene moiety in 48-71% yields and with >98% stereoselectivity. The method is based on intermolecular cyclocondensation of aromatic dicarboxylic acids with α,ω-alka-nZ,(n+4)Z-dienediols (1,12-dodeca-4Z,8Z-dienediol, 1,14-tetradeca-5Z,9Z-dienediol, 1,18-octadeca-7Z,11Z-dienediol) mediated by -(3-dimethylaminopropyl)-'-ethylcarbodiimide hydrochloride (EDC)/4-dimethylaminopyridine (DMAP). The unsaturated diols were prepared by successive homo-cyclomagnesiation of tetrahydropyran ethers of O-containing 1,2-dienes with EtMgBr in the presence of Mg metal and the CpTiCl catalyst (10 mol.%) and subsequent treatment with 0.1 equiv. of para-toluenesulfonic acid of pyran ethers formed after the acid hydrolysis of magnesacyclopentanes. The resulting cyclophanes exhibited high cytotoxic activity in vitro against Jurkat, K562, U937, and HL60 cancer lines. Additionally, the synthesized products were studied for their effect on mitochondria, ability to induce apoptosis, and influence on the cell cycle using modern flow cytometry methods.
开发了一种原始合成路线，用于制备以前未知的含有1Z,5Z - 二烯部分的不饱和聚芳族大环内酯，产率为48 - 71%，立体选择性>98%。该方法基于芳香二羧酸与α,ω - 链烷 - nZ,(n + 4)Z - 二烯二醇（1,12 - 十二碳 - 4Z,8Z - 二烯二醇、1,14 - 十四碳 - 5Z,9Z - 二烯二醇、1,18 - 十八碳 - 7Z,11Z - 二烯二醇）在盐酸-(3 - 二甲基氨基丙基)-'-乙基碳二亚胺（EDC）/4 - 二甲基氨基吡啶（DMAP）介导下的分子间环缩合反应。不饱和二醇是通过在镁金属和CpTiCl催化剂（10 mol.%）存在下，用EtMgBr对含O的1,2 - 二烯的四氢吡喃醚进行连续的均环镁化反应，然后用0.1当量的对甲苯磺酸处理镁杂环戊烷酸水解后形成的吡喃醚而制备的。所得的环芳在体外对Jurkat、K562、U937和HL60癌细胞系表现出高细胞毒性活性。此外，使用现代流式细胞术方法研究了合成产物对线粒体的影响、诱导凋亡的能力以及对细胞周期的影响。
