Study On The Synthesis Of Rare Sugars L-galactose And L-fucos

Carbohydrate is the main source of energy to maintain life activities,and also the main structural component of organisms.With the improvement of modern pharmaceutical research technology,the biological activity and drug activity of carbohydrate compounds have been paid more attention.Carbohydrates are widely used in many major fields,such as anti-tumor,antiviral,prevention and treatment of cardiovascular diseases,the treatment of immune system diseases and anti diabetes,with more diverse biological activity and less side effects,the scope of their application is still expanding.At present,most of the compounds directly isolated from natural products are secondary metabolites of sugar compounds.Bioactive monosaccharides,polymerized sugars or glycosides are also hot topics in the field of traditional Chinese medicine.However,the complex structure of carbohydrate is complex,and the main difficulties in synthesis are regional selectivity,stereoselectivity and synthesis yield.In addition,the saccharides have microscopic heterogeneity,large polarity,difficult to crystallize,and no ultraviolet absorption,which makes it difficult to extract,isolate and identify.It is challenging to efficient preparation of carbohydrate.Uncommon sugars is a kind of monosaccharide and derivative which is very little content in nature.In recent years,uncommon sugars has played an important role in medicine,diet,cosmetics and other fields due to its unique biological activity and low toxicity.L-galactose is a rare six carbon aldose,L-galactose and its derivatives are the main structural units of galactoman,it is found in algae and other plant,L-galactose is also a synthetic intermediate of vitamin C.L-fucose is 6-deoxy-L-galactose,exists in some bacteria and plants glycoside and polysaccharide,plays a main role in cell adhesion in biology,also can be used as a tumor marker in clinical test.Because of the rare content in nature and the immaturity of the existing preparation technology,L-galactose and L-fucose in China are still dependent on import,it is expensive and limites the wider and deeper research in the field of biological medicine.In this project,we studied the synthesis design and process optimization of L-galactose and L-fucose,and completed the following works.①L-galactose was synthesized by eight step reactions from D-galactose via isopropyl group and benzyl group protection,the selective hydrolysis reaction to remove the isopropryl group,then reduction,acetylation protection,deprotection of benzyl group,and oxidation and deacetylation.The yield was 12.1%,The separation and identification of intermediates are 1,2,3,4-Di-O-isopropylidene-D-galactose,1,2,3,4-Di-O-isopropylidene-6-O-benzyl-D-galactose,1,2,3,4,5-penta-O-acetyl-6-O-benzyl-D-galactitol,1,2,3,4,5-penta-O-acetyl-D-galactitol.②pectin was used as raw material to prepare Lgalactohydronic acid through enzymatic hydrolysis.Then L-galactose was synthesized from L-galactohydronic acid by three steps via reduction,dehydration and reduction.The yield was 31.4%.Two important active intermediates of D-galacturonic acid,L-galactonic acid-1,4-lactone were obtained.③ L-fucose was synthesized by eight step reactions from D-galactose via isopropyl group and benzyl group protection,the selective hydrolysis reaction to remove the isopropryl group,dithioacetal reaction,and acetylation protection,deprotection of ethylthio group and benzyl group with Raney nickel,followed by oxidation and deacetylation.The yield was 12.4%.The separation and identification of intermediates are 1,1-S,S’-diethyl-6-O-benzyl-D-galactose thioacetal,1,1-S,S’-diethyl-2,3,4,5-tetraO-acetyl-6-O-benzyl-D-galactose thioacetal,2,3,4,5-tetra-O-acetyl-L-fucitol.④Optimization of synthetic route was made from reaction reagents,temperature,time,catalyst and post treatment,and the optimum enzymatic hydrolysis process of pectin was established by orthogonal experiment design.The synthetic route of L-galactose is simpler,more economical and efficient than the reported route.The synthetic route of L-fucose has not been reported in the literature.This study can provide technical support for low cost and high efficiency production of L-galactose and L-fucose,and expand its application in the field of biomedicine.