118525-40-9Relevant articles and documents
Synthesis of icariin from kaempferol through regioselective methylation and para-Claisen - Cope rearrangement
Mei, Qinggang,Wang, Chun,Zhao, Zhigang,Yuan, Weicheng,Zhang, Guolin
, p. 1220 - 1225 (2015)
The hemisynthesis of the naturally occurring bioactive flavonoid glycoside icariin (1) has been accomplished in eleven steps with 7% overall yield from kaempferol. The 4?-OH methylation of kaempferol, the 8-prenylation of 3-O-methoxymethyl-4?-O-methyl-5- O-prenyl-7-O-benzylkaempferol (8) via para-Claisen-Cope rearrangement catalyzed by Eu(fod)3 in the presence of NaHCO3 , and the glycosylation of icaritin (3) are the key steps.
Magnesium dicarboxylates promote the prenylation of phenolics that is extended to the total synthesis of icaritin
Fu, Xuewen,Lu, Xiaoxia,Wang, Chun,Wen, Yongju,Xiong, Wei,Zhang, Guolin,Zhang, Jichao
, p. 1117 - 1124 (2022/02/16)
The prenylation of phenolic substrates promoted by magnesium dicarboxylates was developed. An investigation of the scope demonstrated that substrates with electron-donating group(s) gave better yields than those with electron-withdrawing group(s). Althoug
Convenient and efficient total synthesis method for icaritin and derivatives of icaritin
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Paragraph 0063; 0084-0088, (2020/02/06)
The invention belongs to the field of natural medicine synthesis and particularly relates to a convenient and efficient total synthesis method for icaritin and derivatives of icaritin. The specific technical scheme is as follows: 2'-hydroxyacetophenone and benzaldehyde are used as raw materials, firstly, isopentene groups are introduced in aromatic rings of raw materials under the catalysis of anorganic polyacid metal ion complex, a flavonol framework is constructed under mild and green conditions, and an isopentenyl flavone compound comprising the icaritin and derivatives of icaritin is further synthesized. The method effectively overcomes the limitation of poor substrate solubility and poor regioselectivity when flavone is constructed firstly and then isopentene groups are introduced, the problems of frequent introduction and removal of protecting groups in a conventional isopentenylation method are solved, and the synthesis route is greatly simplified; and meanwhile, the problems of complex products and more byproducts in an isopentene group rearrangement method are solved. The total synthesis method provided by the invention is mild in condition, convenient to operate, high intotal yield and suitable for mass production of the isopentenyl flavone compound.
Exploration of icariin analog structure space reveals key features driving potent inhibition of human phosphodiesterase-5
Chau, Yasmin,Li, Fu-Shuang,Levsh, Olesya,Weng, Jing-Ke
, (2019/09/30)
The natural product icariin inhibits human phosphodiesterase-5 (PDE5) and represents a unique pharmacophore for treating erectile dysfunction, pulmonary hypertension, and other diseases. In this study, we explore the available icariin-derived chemical scaffolds through medicinal chemistry to develop novel icariin PDE5 inhibitors with improved potency and specificity. We synthesized six novel semi-synthetic icariin analogs as well as three naturally occurring icariin analogs, and characterized the structure-activity relationship in the context of human PDE5 inhibition using in vitro enzyme inhibition and kinetics assays and molecular modeling. Mammalian-cell-based assays and in vitro enzyme inhibition assays against human PDE6C further helped to identify the most potent and selective icariin analogs. Our results reveal the synergistic contribution of functional groups at the C3 and C7 positions of the icariin backbone towards PDE5 inhibition. Whereas a hydrophobic and flexible alkanol group at the C7 position is sufficient to enhance icariin analog potency, combining this group with a hydrophilic sugar group at the C3 position leads to further enhancement of potency and promotes specificity towards PDE5 versus PDE6C. In particular, compounds 3 and 7 exhibit Ki values of 0.036 ± 0.005 μM and 0.036 ± 0.007 μM towards PDE5 respectively, which are approaching those of commercial PDE5 inhibitors, and can effectively reduce GMP levels in cultured human BJ-hTERT cells. This study identifies novel icariin analogs as potent and selective PDE5 inhibitors poised to become lead compounds for further pharmaceutical development.