Green Preparation Of Gold Catalysts And Synthetic Studies On The Glycero-D-manno-Heptose-containing Oligosaccharide Antigens Of Pathogenic Bacteria

Gold catalysis has become a hotspot and research on gold has been continuously reported in the fields of chemistry(catalysts,etc.)and biology(anti-cancer effect,etc.).Traditional synthesis of organophosphine Au(I)complexes inevitably required the use of pungent odor sulfur reagents such as dimethyl sulfide,dipropyl sulfide,and tetrahydrothiophene,or thiodiethanol that has been strictly controlled.These caused great inconvenience in both scientific research and production.In this topic we had invented a new green preparation method.By using 4,4'-thiodiphenol which was basically odorless and inexpensive,we had synthesized a series of commonly used gold catalysts and also synthesis of anti-rheumatoid arthritis drug auranofin.As a Gram-negative bacterium,H.pylori has been observed in the stomach a century ago.More than 30 years ago,Barry Marshall and Robin Warren proved that Helicobacter pylori has a close relationship with gastric ulcer and gastric cancer.The main treatment method is to use antibiotics to deal with such bacteria,but it has the disadvantages of poor drug resistance and patient compliance.Researches found that 1,3-linked D-glycero-D-manno-heptose exists in many strains of H.pylori.Using our de novo synthesis method,we successfully constructed the orthogonally protected D-glycero-D-manno-heptose block through two aldol addition reactions.With the method of gold-catalyzed ?-stereoselective glycosylation of manno-heptose o-alkynyl benzoate,we established ?-1,3 glycoside bonds between D-glycero-D-manno-heptose blocks,and completed the total synthesis of the trisaccharide antigen on the surface lipopolysaccharide various strains of H.pylori.We also got the corresponding monosaccharide and disaccharide antigens.The Gram-negative bacterium Vibrio parahaemolyticus isolated from the ocean often causes a series of symptoms such as abdominal pain,diarrhea,and vomiting.In 2003,Kondo's group reported that there is a unique high carbon sugar structure on lipopolysaccharide of Vibrio parahaemolyticus O2 type,which contains L-glycero-D-manno-heptose,D-glycero-D-manno-heptose and Kdo.Using a new synthesis method,starting from L-lythose and D-ribose,we efficiently constructed orthogonally protected L-glycero-D-manno-heptose and D-glycero-D-manno-heptose blocks and finally synthesized the unique trisaccharide antigen of the lipopolysaccharide of Vibrio parahaemolyticus O2 through a linear synthesis.Heterotrophic bacteria.Alteromonas macleodii living in the ocean have been found to have denitrification,which has great value in sewage treatment and other aspects.In 2006,Parrilli's group reported the structure of the R-type lipopolysaccharide of Alteromonas macleodii ATCC 27126T strain,which contains two stereo configurations of Kdo and L-glycero-D-manno-heptose.Based on the above synthesis method,we synthesized a 7-position selectively protected L-glycero-D-manno-heptose donor,and successfully established a 1,5-linked glycosidic bond with the 5-position hydroxyl group of Kdo,finally obtained key disaccharide fragments.Then we explored the use of a glycosylation reaction of the Kdo o-alkynylbenzoate donor to construct a trisaccharide fragment containing two Kdo and one L-glycero-D-manno-heptose.