Synthesis And Glycosylation Of An N,N-diacetylimido Protected Thioglucosamine

As important components of natural occuring carbohydrates,amino sugars are widely spread in animals,plants and microorganisms,and play important roles in biological functions such as signal transduction,genetic development and targeted recognition.Glucosamine is one of the most abundant monosaccharides in nature,and it is widely present in the form of N-acetyl derivatives.It is an important precursor of lipid and glycoprotein and has a wide range of biological activities.In natural oligosaccharides,amino sugars are coupled with many other suger units via β-glycosidic bond by selecting appropriate amino protecting groups and glycosylation methods to construct the 1,2-trans coupling is very important for syn-thesis of HMOs and other oligosaccharides.Koenigs firstly proposed the acetyl protecting group could direct β selectivities and to avoid the side product of the oxazoline and increase the reaction efficiency,many other protecting strategy have been developed there after.Phthalimido group is a common amino protecting group nowadays,but its deprotection requires high temperature in alkaline conditions,and usually leads to the partially decomposition of glycosidic bonds.Schmidt reported a diacetyl-protected thiomethyl donor with peracetyl protection.When the disarmed donor reactded with less reactive acceptors,acyl migration occured,the oxazolidine byproduct increaseed,and poor the glycosylation was yielded.The purpose of this thesis is to optimize N,N-diacetyl as the amino protecting group to construct a novel "armed" glucosamine donor,because of the neighboring group of N,N-diacetyl,the β glycosidic bond is constructed.The acetyl group can be efficiently removed by mild conditions,and the other protecting groups are not affected.Through the concentric dual cell NMR experiment,the trends of receptors along the concentration of Lewis acid are compared,and the glycosilation are further optimized.Chapter 1 briefly reviewed the current progess of glucosamine protection,the mechanisms and applications of glycosylation methods,and principle of isotope exchange reaction.In glycosylation,most amino protecting groups control the stereo-selectivity through the neighboring group participation.For non participation groups,such as azide,the stereoselectivity is determined by specific conditions.In Chapter 2,the N,N-diacetyl-protected "arme" donor 3 was synthesized in five-steps.In the presence of NIS and acid,the high yields of 1,2-trans disaccharide product is formed with higher dose of Lewis acid.In the concentric dual cell NMR experiment,acceptors can compete with NIS for protons in the system.The primary alcohol acceptor 5 forms intermolecular hydrogen bonds,and shows a more sensitive nonlinear growth toward the acid change.While the secondary alcohol acceptor 4 forms intramolecular hydrogen bonds,and shows a less sensitive linear growth toward the acid change.