Stereoselective Construction Of N-glycosyl Trichloroacetamide And Its Application In The Synthesis Of Glycosyl Ureas

Glycosylureas are a kind of compounds in which the traditional C-O and C-N glycosidic bond are replaced by a carbamic bond.The introduction of the carbamic bond increases the compatibility of these compounds with enzyme hydrolysis and chemical reagents while still maintaining the bioactivities of the natural carbohydrates.Many glycosylureas have good pharmacological activities,and thus can be used as lead compounds for the development of aminoglycoside antibiotics and anti-diabetic agents.Moreover,glycosylureas are also able to serve as small-molecule H-bond donors in the asymmetric catalytic reactions.In view of the significance of glycosylureas,the synthetic methods for this kind of compounds have been reported successively,mainly including direct coupling of sugar with urea,preparation from amino sugar precursor,synthesis via glycosyl isocyanate intermediates and so on.Each of these methods has their own advantages,but also has some shortcomings,such as use of harmful heavy metal catalysts or reagents,poor stereoselectivity and so on.Therefore,it is necessary to develop an environmentally friendly strategy for stereoselective construction of glycolurea compounds.In this thesis,by employing Ferrier rearrangement and Overman rearrangement,we have established a green approach to efficient installation of ?-and ?-N-glycosy trichloroacetamides.This new method has notable features,such as good stereoselectivity,green reaction conditions,and wide substrate applicability.Therefore,it will play an important role in the synthesis of glycosylureas with potential bioactivities.The thesis mainly contains three parts:1.Stereoselective construction of thermodynamically stable ?-N-glycosy trichloroacetamide via Ferrier rearrangement;2.Stereoselective construction of ?-and ?-N-glycosy trichloroacetamide via Overman rearrangement using 3-position group in 1,2-glycal substrate as a guide group.3.Application of the prepared N-glycosy trichloroacetamides in the synthesis of glycosylureas.The details are as follows:1.The Ferrier rearrangement is a type of allylic rearrangement,which provides an important tool for the preparation of 2,3-unsaturated glycosides.In part I,we have developed a stereoselective method for the construction of ?-N-glycosy trichloroacetamides based on Ferrier rearrangement.Thermodynamically stable?-N-glycosyl trichloroacetamides could be obtained with good stereoselectivity and excellent yields when using 3-O-trichloroacetimide as substrate and copper trifluoromethanesulfonate as catalyst at-20? for 30 min.Under this optimal conditions,13 different ?-N-glycosy trichloroacetamides were synthesized,the structure of which were firmly confirmed by NMR and HRMS analysis.2.Overman rearrangement,a variant of Claisen rearrangement,is one of the important methods for the formation of C-N bond.In part II,on the basis of Overman rearrangement,we have developed a facile access to both ?-and ?-N-glycosy trichloroacetamides through tuning the configuration of 3-position group in 1,2-glycal substrates.Under the optimal reaction conditions,13 different ?-and ?-N-glycosy trichloroacetamides were prepared in excellent yields and high stereoselectivity with unambiguous structure assignments.3.Glycosylureas have attracted much attention due to their unique structures and good bioactivities.Delightedly,our synthesized 2,3-unsaturated glycosyl trichloroacetamides are readily to be used as important precursors for the synthesis of glycosylureas.Moreover,because of containing an olefinic bond,structurally diverse glycosylurea compounds can be achieved by functionalizing the double bond in 2,3-unsaturated glycosyl trichloroacetamides.In conclusion,we have developed a facile and green method to prepare 2,3-unsaturated glycosyl trichloroacetamides by Ferrier rearrangement and Overman rearrangement.A variety of thermodynamically stable ?-N-glycosy trichloroacetamides were synthesized with good to excellent yields and high anomeric selectivity by acid-catalyzed Ferrier rearrangement.A series of ?-and ?-N-glycosy trichloroacetamides were also obtained by Overman rearrangement via six-membered cyclic transition state,combined with the configuration control of 3-position group in 1,2-glycal substrates.Our prepared 2,3-unsaturated glycosyl trichloroacetamides were further applied in the synthesis of glycosylureas.