De Novo Synthesis Of L-fucose And Efficient Synthesis Of Nucleosides

L-Fucose,widely distributed in seaweed and gum,is a common component of many glycolipids and N-and O-linked glycans in mammalian cells.Fucose and fucosylated glycans are widely investigated due to the important functions such as signal transduction,anti-inflammatory and anti-cancer.In order to promote the development of fucose-containing drugs and therapeutic agents,sufficient pure and well-defined fucose-containing carbohydrates are required to evaluate their activities.L-fucose provides important material for the synthesis of fucose-containing carbohydrates.At present,L-fucose is mainly produced by enzyme-promoted synthesis,extraction from natural fucoidans and chemical synthesis.The chemical synthesis of L-fucose mainly focuses on the conversion of other common monosaccharides,which faces several problems such as long synthetic routes,high costs,and low total yields,thus limiting the biological studies of fucosylated glycans.In the first part of this work,we developed an economic and efficient de novo approach for the synthesis of L-fucose,which provides L-fucose in 12%overall yield through ten steps with cheap and readily available L-ethyl lactate as starting material.This approach features D-proline-promoted diastereoselective aldol reaction as key step for the construction of a six-carbon skeleton and TEMPO-catalyzed NCS regioselective and chemoselective oxidation as another key step for the construction of aldehyde group in target molecular.Nucleosides,usually composed of bases and ribose or deoxyribose,play an important role in enzyme metabolism and regulation,cell signaling,DNA and RNA synthesis.Nucleosides also have excellent performance in antivirus and antitumor.Efficient methods for the synthesis of nucleosides are essential to understand their mechanisms for the development of therapeutic agents.Although some effective methods for the synthesis of nucleosides have been reported,N-glycosylation of pyrimidines and purines,especially the N9/N7 regioselective glycosylation of purines,remains challenging due to the poor nucleophilicity and solubility of nucleobases.In the second part of this work,we described a novel NIS/TMSOTf-promoted N-glycosylation of glycosyl ynenoates.Based on the present method,a series of pyrimidine nucleosides and N9 purine nucleosides,which lays a foundation for the further biological studies.This glycosylation method has the advantages of stable donor,mild reaction conditions,good yields and wide substrate scope,may find wide application in the synthesis of various types of nucleosides.