title: 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.
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Pan
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Lianbo
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 211198, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Xiao
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Yantao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: College of Chemistry, Tianjin Key Laboratory of Structure and Performance for Functional Molecules, Tianjin Normal University, Tianjin, 300387, PR China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: College of Food Engineering and Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Zhenchuan
authors.initials: Z
authors.lastname: Fan
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, PR China.
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 382 Longvalley Lane, DeKalb, IL 80115, USA.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Yao
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, PR China. Electronic address: lukui@tust.edu.cn.
authors.forename: Kui
authors.initials: K
authors.lastname: Lu
authors.affiliation: China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, Key Lab of Industrial Fermentation Microbiology, Tianjin Key Lab of Industrial Microbiology, Sino-French Joint Lab of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science and Technology, Tianjin, 300457, PR China. Electronic address: yupeng@tust.edu.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Yu
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000478:Alkylation; D000818:Animals; D047310:Apigenin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005947:Glucose / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice
chemical_list: D007004:Hypoglycemic Agents; D047310:Apigenin; D005947:Glucose
keywords: 8-(6′′-umbelliferyl)-apigenin; Anti-diabetic; Coumarins; Flavonoid; Suzuki coupling reaction