An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssino...An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.展开更多
A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin（1）,6,8-dimethylgenistein（2） and their analogues（3-8） is established for the first time.The synthesis is realiz...A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin（1）,6,8-dimethylgenistein（2） and their analogues（3-8） is established for the first time.The synthesis is realized in 7-8 steps in overall yields of 16%-24%from commercially inexpensive phloroglucinol and features a high yielding Vilsmeier-Haack reaction,Friedel-Crafts acylation,Gammill＇s protocol and Suzuki coupling as the pivotal transformations.Next,these compounds evaluated for their inhibitory potency on the production of nitric oxide（NO） in lipopolysaccharide（LPS）-activated RAW-264.7 cells as an indicator of anti-inflammatory activity.The results showed that all the compounds decreased NO production in a dose-dependent manner without marked cytotoxicity and IC_（50） values are found in the range of 10.17-33.88 μmol/L.Of note,compounds 3 followed by 1,7 and 8 show comparable inhibitory activity with positive control（N-monomethyl-L-arginine,L-NMMA）.展开更多
基金financially supported by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. NRF-2009-0094071), South Korea
文摘An efficient approach has been developed for the synthesis of naturally occurring prenylated chalcones viz. kanzonol C （1）, stipulin （2）, crotaorixin （3）, medicagenin （4）, licoagrochalcone A （5） and abyssinone D （6） along with the pyranochalcones paratocarpin C （7）, anthyllisone （8） and 3-O-methylabyssinone A （9）. The key step of the synthesis is a Claisen-Schmidt condensation. Subsequently, their anti-inflammatory effects were investigated in lipopolysaccharides （LPSs）-induced RAW-264.7 macrophages. Of the synthesized chalcones, compounds 5 （IC50= 10.41 μmol[L）, 6 （IC50= 9.65 μmol/L） and 8 （IC50= 15.34 μmol/L） show remarkable activity with no cytotoxicity. Compound 9 （IC50 = 4.5 μmol/L） exhibits maximum （83.6%） nitric oxide （NO） inhibition, but shows slight cytotoxicity. The results reveal that the chalcones bearing the prenyl group at 3- and/or 5-position on ring A （acetophenone moiety）, i.e., 1-4 and 7 show weak, or no inhibition activity, whereas chalcones having the prenyl group only on ring B （aldehyde part）, i.e., 5, 6 and 8 show significant activity on the production of inflammatory mediated NO with no cytotoxicity.
基金financially supported by industrial co-work program with Sun Chem(Sun Kyung Chemical Co.,South Korea)
文摘A modular and efficient synthesis of the biologically significant C-methylisoflavones isosideroxylin（1）,6,8-dimethylgenistein（2） and their analogues（3-8） is established for the first time.The synthesis is realized in 7-8 steps in overall yields of 16%-24%from commercially inexpensive phloroglucinol and features a high yielding Vilsmeier-Haack reaction,Friedel-Crafts acylation,Gammill＇s protocol and Suzuki coupling as the pivotal transformations.Next,these compounds evaluated for their inhibitory potency on the production of nitric oxide（NO） in lipopolysaccharide（LPS）-activated RAW-264.7 cells as an indicator of anti-inflammatory activity.The results showed that all the compounds decreased NO production in a dose-dependent manner without marked cytotoxicity and IC_（50） values are found in the range of 10.17-33.88 μmol/L.Of note,compounds 3 followed by 1,7 and 8 show comparable inhibitory activity with positive control（N-monomethyl-L-arginine,L-NMMA）.
