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

• A novel flavone 8-(6″-umbelliferyl)apigenin were synthesized for the first time.
• Regio-selective iodination and Suzuki coupling reactions were used as key steps.
• Analogues with different flavonoids cores were synthesized.
• Effects of these compounds on glucose disposal were investigated in adipocytes.
• The most potent could promote glucose consumption by 57% in 10 μΜ.

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.

A novel flavone 8-(6″-umbelliferyl)apigenin and its analogues were synthesized for the first time. The anti-diabetic activity evaluation results revealed these compounds could promote glucose consumption in adipocytes.Figure optionsDownload as PowerPoint slide