| C-Glycosides,in which a glycosyl moiety is directly linked to an aglycone via a C–C bond,are commonly presented in natural products and drugs.Functionally,carbon glycosides can simulate the biological functions of O/N-glycosides,while improving stability and improving the medicinal properties O/N-glycosides,which has attracted much attention.However,in most cases,the oxygen and nitrogen atoms in O/N-glycosides have weak bond interactions with specific target proteins,so it is necessary to develop new carbon glycosides that mimic the heteroatoms in natural oxygen/nitrogen glycosides as much as possible to improve their corresponding biological functions.Related investigations found that C-hydroxymethine glycoside might be a better mimetic than previous C-glycosides.However,due to the tremendous structural and functional diversity,C-glycoside bearing a chiral hydroxymethine motif has yet to be fully explored due to the limited method to construct these complex compounds.This dissertation focuses on new and efficient synthetic methods to construct asymmetric C-hydroxymethine glycosides.After feasible transformations,the corresponding C-glycosides can provide versatile glycosyl skeletons with crucial physiological and pharmacological activities,including 2,3-dideoxyglycosides,allosides,mannosides,Altrosides and their2-substituted derivatives,to provide a material basis for our group to further explore the biological functions of these C-glycoside.The dissertation contains the following four chapters:Chapter 1: Synthesis background of chiral C-hydroxymethine glycosides(review)In this chapter,the progress in the synthesis of hydroxymethine glycosides is briefly introduced,and the research on their synthesis in recent decades is described according to the classification of the properties of glycosyl donors.Chapter 2: Synthesis Study of Chiral C-Hydroxymethine GlycosidesUsing chiral Cu(Ⅰ)-NHC complex,glycal tert-butyl carbonate and pinacol diborate were used as raw materials to construct glycal boronate at C-3 position with stereoselectivity.The catalysis is not affected by the stereochemistry of isobutyl carbonate and sugar C5-position,and the diastereoselectivity is controlled by the glycal C4-position stereocenter and chiral NHC ligand,to produce the glycal borate intermediate at C3-position.Then,a one-pot strategy was used to generate C-hydroxymethine glycosides by Allylation between glycal boronate and aldehydes with highly diastereoselective.This method can construct a series of chiral C-hydroxymethine glycosides by regulating the chirality of NHC ligand,glycosyl source,and aldehyde.At the same time,the generated C-hydroxymethine glycosides contain double bonds,which can be further functionalized and synthesized to produce various C-hydroxymethine glycosides in a divergent manner.Chapter 3: Synthesis and Application of [2,3]–β-DehydrosugarsBased on the synthesis of C-hydroxymethine glycosides by Cu(Ⅰ)-NHC catalytic system,a series of [2,3]-dehydro-C-hydroxymethine glycosides were obtained.After feasible transformation,the corresponding C-glycosides can be derived into multifunctional glycosyl skeletons with important physiological and pharmacological activities,including 2,3-deoxyglucoside,allosides,mannosides,altrosides and its2-substituted derivatives,to make material foundation for the later development of biological functions.Chapter 4: Asymmetric Total synthesis of indole alkaloid(-)-17-nor-ExcelsinidineThe content of this chapter is the preliminary work of the doctoral study stage.Firstly,a brief introduction is given to the separation,biogenic hypothesis,and related synthesis background of(-)-17-nor-Excelsidine.Based on the characteristics of molecular skeleton,the key piperidine ring skeleton was successfully constructed by palladium catalyzed reductive Heck reaction with good cis-selectivity;the key N4-C16 bond was connected through oxidative coupling from the key intermediate geisoscizine,and(-)-17-nor-Excelsidine was synthesized with excellent yield and high regioselectivity. |
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