Design Synthesis and Biological Study of Pinacolylboronate-Substituted Stilbenes as Novel Lipogenic Inhibitors

摘要

A series of novel 4,4,5,5-tetramethyl-2-(4-substitutedstyrylphenyl)-1,3,2 dioxaborolane derivatives has been synthesized. 4-(4,4,5,5-tetramethyl-1,3,2-dioxaboratophenyl)-methyl triphenylphosphonium bromide (4) was treated with 3 equiv of ^tBuONa, various aldehydes in the presence of DMF, and stirred at room temperature 4–6 hrs to yield the corresponding boron containing stilbene derivatives in 71–94% yields. A one-pot protocol transformation has also been developed and used to synthesize boron-containing compounds. Several of them, including BF102 and BF175, have the effect of inhibiting lipogenesis by suppressing lipogenic gene expression in mammalian hepatocytes. Moreover, BF102 also inhibits cholesterol biosynthesis by suppressing HMG-CoA reductase gene expression in hepatocytes. Thus, BF102 is a potential lead for the next generation of lipid-lowering drugs.