| Diabetes mellitus is a series of clinical syndromes caused by absolute or relative insufficiency of insulin in vivo,which seriously threatens human health and affects the quality of life.It is particularly necessary to find stable and reliable Hypoglycemic Active ingredients.Carambolaflavone A,a natural flavonoid,is a carbohydrate flavonoid with hypoglycemic activity extracted from carambola leaves.The first total synthesis of Carambolaflavone A and its enantiomers was achieved in 12 longest linear steps by Suzuki-C glycosylation with total yields of 16%(L-fucose)and 11%(D-fucose),respectively.The adverse effects of 4AMS on Suzuki-C-glycosylation reaction were revealed through comprehensive investigation.The transformation process of phenolic hydroxyl groups containing hydrogen bonds in Suzuki-Cglycosylation was clarified,and the real structure of Carambolaflavone A was finally determined.The virtual screening of alpha-glucosidase inhibitor from the molecule library of sugar drugs obtained Z10 which was proposed to be a new type of Hypoglycemic Active drug.Further structural optimization of Z10 generated our target molecule Z10’ which will be prepared via RCM mediated penta-carbon-cyclization using Dribose as chiral source,The construction of Z10’ molecular skeleton by Suzuki coupling would facilitate the bioactivity tests and verify the rationale of the calculation method by Computer Aided Drug Design. |
