Total synthesis of 8-(6″-umbelliferyl)-apigenin and its analogs as anti-diabetic reagents.

Abstract The naturally occurring flavone 8-(6″-umbelliferyl)apigenin, a hybrid structure of apigenin and coumarin, as well as seven of its analogues were synthesized for the first time by using iodination and Suzuki coupling reactions as key steps. The synthesis of 8-(6″-umbelliferyl)-apigenin was achieved in seven linear steps from the commercially available 1-(2,4,6-trihydroxyphenyl)ethan-1-one and 7-hydroxyl coumarine with 31% overall yield. Effects of these compounds on glucose disposal were investigated in adipocytes. All of the flavonoid and coumarin hydrids were found to have better bioactivities than their corresponding flavonoid cores. The most potent compound 15 (10 μΜ) could promote glucose consumption by 57% which exhibited similar effect as the positive control metformin at 1 mM. Moreover, fluorescence microscopy showed that four 8-(6″-umbelliferyl)apigenin analogues 2 , 15 , 30 and 31 could promote the 2-NBDG uptake into 3T3-L1 cells, which consist with those observed in the regulation of glucose.