Study On The Synthesis And Bioactivities Of Analogs Of Shuangkangsu-an Active Principle Of Jinyinhua

Shuangkangsu, a new component with unusual 1,2-dioxane skeleton first isolated by our group from Jinyinhua, one of TCM (traditional Chinese medicine) has a significant activity of inhibition of influenza virus in chicken embryo and respiratory syncytial virus in cells. The particular skeleton of the leading compound is valuable for new drug research and development.For studying the total synthesis of Shuangkangsu and its analogs, in this work, the methods for the formation and glucosylation of [1,2]dioxane-3,6-diol as well as the method for removal of acetyl protective group in compounds 26a, 26b have been studied. Analogs of Shuangkangsu were synthesized and tested for antiviral activities. Meanwhile, some reaction mechanisms in this work have also been studied.1. The method for the formation of [1,2]dioxane-3,6-diol, which is intramolecular addition of hydrogen peroxide to 1,2-dialdehyde was established. The effect of substituents in aromatic ring on the formation of [1,2]dioxane-3,6-diol was firstly discussed. Electron-withdrawing substituents can promote the formation of [1,2]dioxane-3,6-diol, and vice versa.2. The pure homochiral analogs 30a, 30b of Shuangkangsu were successfully synthesized from compound 19. The glucosylation methods for hydroxyl of substrate 19 was developed: The substrate 19 reacted with the alkyl thioglycoside donor by treat with N-Iodosuccinimide and Silver Trifluoromethanesulfonate, or reacted with the glycosyl trichloroacetimidate donor by treat with boron trifluoride ether complex. The method for removing the acetyl protective group in 3,6-O-glycosyl-[1,2]dioxane was firstly studied. Dibutyltin oxide was the proper reagent to remove the acetyl protective group in compounds 26a, 26b. By comparison the CD spectra of compounds 29a, 29b and Shuangkangsu, the absolute configuration of 30a, 30b were determined to (1R, 4R) and (1S, 4S). 3. Some analogs of Shuangkangsu were tested for antiviral activities, the structure-activities relationship (SAR) and antiviral mechanism of this kind of compounds were firstly discussed.4. The decomposition mechanisms of the peroxides under acidic or basic conditions were firstly discussed.5. A novel reaction, pyridine ring reduced by sodium borohydride, was observed and the reaction mechanism was firstly discussed.