Synthesis And Anti-tumor Activity Of Glycosylated Derivatives Of Diosgenin

Due to the complexities and diversities of their structure,carbohydrates can not only provide energy as a structural skeleton and life activities of organisms,but also be the third important living substance other than proteins and nucleic acids,and serve as intercellular recognition and communication molecules.At the same time,carbohydrates participate in the whole process from fertilization to aging.In addition,the distribution of glycosylation of natural products is also extensive,and the glycosyl moiety has an effect of increasing solubility,increasing binding rate,and regulating half-life.Therefore,the research heat of glycosylation modification of natural products is increasing.Diosgenin is widely found in legumes and yam plants.It is mainly obtained from plant tubers such as Dioscorea zingiberensis and Dioscorea zingiberensis by hydrolysis,fermentation and extraction.It is generally used to produce pregnenolone and progesterone.Modern researches show that diosgenin has anti-tumor,anti-AIDS,hypoglycemic,anti-arteriosclerosis,anti-oxidation,anti-arthritis;protection of gastric mucosa,sputum,enhancement of cardiac contractility,improvement of microcirculation and other effects.Diosgenin and furosemide also possesse physiological activities similar to aglycones.For example,the main component of Di'ao Xinxuekang is water-soluble diosgenin extracted from Dioscorea opposita Thunb.At the same time,there are many reports on the synthesis of disaccharide,trisaccharide and even polysaccharide chain diosgenin by convergent synthesis strategy or linear stepwise synthesis strategy.However,it is still limited by factors such as low yield,cumbersome reaction steps,and complicated operation.In recent years,the chemical modification of glycosylation diosgenin compounds has been dominated by O-glycosylation.The O-glycosylation modification methods are mainly the classical Koenigs-Knorr method and the Schimt method.Both methods have many advantages,but they all have disadvantages such as cumbersome steps and low efficiency.In 1998,the random aglycosylation of methoxyamine appeared,and in 2005 introduced structural modification of cardiac glycosides,such methods with reducing sugars as sugar donors,and methoxyamino substituted aglycones The glycosidic reaction is directly carried out under acidic conditions,and a large amount of azinium compound is obtained quickly and efficiently,thereby avoiding the steps of protecting,substituting,and deprotecting the sugar during the O-glycosylation reaction.At present,the diosgenation of the diosgenin remains in the O-glycosylation modification,and N-glycosylation is hardly reported.In this study,diosgenin was used as a raw material to prepare a more stable furazan saponin and a dimethoprim-substituted diosgenin for the first time,using D-glucose,D-galactose,L-rham Eight common sugars,such as sugar,were introduced into the rare sugar L-fucose to complete the following work:(1)For the first time,9 kinds of 3 diosgenin monoglycosides were synthesized by Koenigs-Knorr method,and the synthesis was difficult.The monosaccharide is subjected to a glycosidic reaction by a boron trifluoride diethyl ether catalyzed reaction,which greatly improves the reaction efficiency products including:3-O-?-D-glucose diosgenin,3-O-?-D-galactose diosgenin,3-O-?-L-arabinose diosgenin,3-O-?-L-rhamnose diosgenin,3-O-a-L-fucose diosgenin,3-O-p-D-xylose Saponin,3-O-a-L-xylose diosgenin,3-O-?-D-ribose diosgenin,3-O-?-D-mannose diosgenin;(2)Diosgenin by acetic anhydride The hydroxyl group at the 3-position is opened,and the yield is high,the stability is good,and the impurities are small.Subsequently,five kinds of 26 diosgenin monoglycosides were synthesized,including:(25S)-26-O-?-D-glucosyl-furazan-5,(6)-ene-3?-ol,(25S)-26-O-?-D-galactosyl-furazan-5,(6)-ene-3?-ol,(25S)-26-O-?-L-rhamnosyl-furazan-5,(6)-ene-3?-ol,(25S)-26-O-a-L-fucosyrosyl-furazan-5,(6)-ene-3?-ol,(25S)-26-O-?-L-arabinosyl-furazan-5,(6)-ene-3?-alcohol;(3)first synthesis of 7 methoxyamino substituted diosgenin monoglycosides including,diosgenin(3R)-N(MeP)-?-D-glucopyranoside,diosgenin(3S)-N(MeO)-?-D-glucopyranoside,diosgenin(3R)-N(MeO)-?-D-galactopyranoside,diosgenin(3S)-N(MeO)?-D-galactopyranoside,diosgenin(3R)-N(Me?)-?-L-fucopyranoside,diosgenin(3R)-N(MeO)-?-D-mannopyranoside,diosgenin(3S)-N(MeO)-?-L-rhamnopyranoside.Among them,5 kinds of furosein analogues and 7 kinds of diosgenin analogues are new compounds.At the same time,the synthesized products were subjected to hydrogen spectrum and carbon spectrum analysis to confirm the structure.Finally,MTT cell experiments were carried out.The half-inhibition rate of(25S)-26-O-?-L-fucosyrosyl-furazan-5,(6)-ene-3?-ol(51),diosgenin(3S)-N(MeO)-?-D-glucopyranoside(55),diosgenin(3S)-N(MeO)-?-D-galactopyranoside(57),diosgenin(3R)-N(MeO)-?-L-fucopyranoside(58)compounds on tumor cells was less than 50?M,wth an average of 30-40?M,the results of the remaining products were all greater than 50 ?M.The antitumor activity of diosgenin glycosylation derivatives still needs further exploration.