Synthesis, functionalization and biological activity of arylated derivatives of (+)-estrone

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• 作者：Anton Ivanov^a ; Syeda Abida Ejaz^d ; Syed Jawad Ali Shah^d ; Peter Ehlers^a ; ^b ; Alexander Villinger^a ; Eva Frank^c ; Gyula Schneider^c ; Já ; nos Wö ; lfling^c ; Qamar Rahman^e ; Jamshed Iqbal^d ; Peter Langer^a ; ^b ; ^{peter.langer@uni-rostock.de}
• 关键词：Steroids ; Phosphatase inhibition ; Suzuki reaction ; Catalysis
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：25
• 期：3
• 页码：949-962
• 全文大小：1581 K
• 卷排序：25

文摘

Various novel arylated estrone derivatives, such as 2-aryl-, 4-aryl- and 2,4-diaryl-estrones, by Suzuki-Miyaura reactions. While the synthesis of 4-arylestrones could be carried out under standard conditions, the synthesis of 2-arylestrones and 2,4-diarylestrones required a thorough optimization of the conditions and it proved to be important to use sterically encumbered biaryl ligands. The best results were obtained by the use of RuPhos. Combination of developed Suzuki coupling reactions with subsequent cyclization reactions afforded more complex hybrid structures, containing dibenzofuran, benzocoumarin and steroid moieties. These derivatives were tested as pancreatic lipase inhibitors and it was found that most of the compounds exhibited inhibition of pancreatic lipase but the maximum inhibitory potential was shown by 4-arylestrones. All of the synthesized derivatives showed inhibitory values in the range of 0.82 ± 0.01–59.7 ± 3.12 μM. The biological activity was also rationalized on the bases of docking studies.