Selective Synthesis And Modification Of Sugars And Polyol

Carbohydrates and polyhydroxylated natural products have always attracted much attention in the fields of life sciences and medicinal chemistry.In order to study the mechanism and laws of such biologically active molecules in living organisms and their application potential in different disciplines,scientists usually need to modify these biologically active molecules.Unlike the modification of amino acids and nucleotides,there are many challenges in the functional modification of carbohydrates and polyhydroxylated natural products.This is because such compounds often contain multiple hydroxyl groups and the difference in the chemical activity of these hydroxyl groups is extremely small,and each hydroxyl group can be used as a potential chemical reaction site.Therefore,the precise functionalization of carbohydrates and polyhydroxylated natural products has important scientific research significance.In recent years,the application of photocatalytic technology in various fields has made considerable progress.In the past decade,photocatalysis has become a widely used strategy in synthetic chemistry.Many chemical transformations that cannot be achieved by traditional methods can be carried out smoothly under photocatalytic conditions,and many reagents that require stoichiometric use are also replaced by simple oxidants or reducing agents in the photocatalytic system.Photocatalysis has become an important way to develop new green catalytic systems.β-Aryl C-glycosides are found in many important drugs and active natural products.SGLT2 inhibitors used in the treatment of type 2 diabetes are representative drugs that contain β-aryl C-glycosides structural units.However,the existing methods are still difficult to meet the needs that synthesis β-aryl C-glycosides rapidly,directly,efficiently and stereoselectively in practice.Based on the visible light mediated transition metal co-catalysis strategy,the stereoselective preparation ofβ-aryl glycosides via cross coupling of glycosyl chlorides with aryl bromides and arylboronic acids was successfully achieved.The visible light mediated nickel catalytic coupling reaction system is characterized by high stereoselectivity,good cost effectiveness,mild conditions and wide range of substrate applications.It can rapidly obtain a variety ofβ-aryl glycosides for drug development and chemical biology research.Deoxy sugars are ubiquitous in nature and contribute to a diverse repertoire of biological activities.The antigenic epitopes of many antibiotics and some pathogenic microorganisms contain deoxygenated sugars.Therefore,deoxy sugars as a special kind of sugar has very important research value.However,direct deoxygenation of common alkyl alcohols such as sugars remains a challenge.Based on photoredox catalytic strategy,phosphoranyl radicals could be accessed via nucleophilic addition of an alcohol to a phosphine radical cation generated by photoinduced single-electron transfer(SET).Then,phosphoranyl radicals undergo β-scission to form a strong phosphorus-oxygen double bond and a new carbon-centered radical species which followed afford the corresponding deoxygenated product via terminal hydrogen atom transfer(HAT).The method is simple and mild,and can be directly and effectively deoxidized to primary alcohols,secondary alcohols and tertiary alcohols.Moreover,when the Michael receptor such as methyl acrylate exists in the photocatalytic deoxygenation reaction system,the direct deoxyalkylation modification of corresponding alcohols can also be realized.As an important functional group,methyl group is not only widely used in synthetic chemistry and pharmaceutical chemistry,but also plays an important role in many life activities.Therefore,the research of methylation modification methodology has attracted much attention.In the development of visible light mediated deoxygenation of carbohydrates,we unexpectedly discovered a methylation strategy for alcohols by using a trivalent organic phosphine reagent and a Michael receptor.By exploring the reaction mechanism,we developed a new selective methylation modification method based on a modified Arbuzov-Reaction.This method can modify a series of bioactive molecules containing aliphatic alcohol hydroxyl group or phenolic hydroxyl group with high efficiency under extremely mild reaction conditions without the addition of extra strong base.Through the modification of the trivalent phosphine reagent and the Michael receptor in the system,we further realized the selective methylation modification of a series of complex natural active molecules and drug molecules.In addition,we have also successfully implemented NH site selective methylation modifications for bioactive molecules containing nucleoside structural units and O-methylation modifications for a series of small molecules containing carboxyl groups.The comparison with the classical methylation method shows that our methylation modification system not only has good substrate applicability for the O-methylation modification of simple alcohols,but also has unique advantages for the methylation modification of complex natural products.It is worth noting that by adjusting trivalent tertiary phosphines,we have further realized the selective ethylation,butylation,isopropylation,trifluoroethylation and allylation of polyhydroxy compounds on the basis of methylation modification.