Synthesis Of The Tetrasaccharide Repeating Unit Of Group B Streptococcus Serotype ? Capsular Polysaccharide

Bacterial infection has been threatening human physical and mental health.In order to prevent and treat the diseases caused by bacterial infection,many effective measures have been developed.At present,antibiotics are the main means to prevent bacterial infection.However,due to the limitation of material conditions,it is difficult to implement this preventive measure in developing countries.At the same time,with the large-scale usage of antibiotics,the strains have exhibited serious tolerance to antibiotics,reducing the protective effect of antibiotics.In order to reduce the use of antibiotics and deal with the new crisis of bacterial infection,people need to develop more and more effective treatments.Sugar,also known as carbohydrate,is one of the most widely existing substances in nature,and it is also an essential basic material for the energy storage of organisms and their bodies.Starch and cellulose are the most important polysaccharides in plants,while glycogen is the most important polysaccharide in animals.At first,sugar was only used as a necessary nutrient for human body,and it was the main source of energy for all organisms to maintain life activities.With the continuous progress of science and technology,chemists and biologists gradually discover that carbohydrate plays multiple roles in organisms,and participates in various physiological processes of cells through various forms,including cell recognition,cell migration and adhesion.There are many types of sugars and related substances in bacteria,which play an important role in bacteria recognition,signal transmission,adhesion,infection,and defense,etc.Because of the highly specific immunogenicity of carbohydrate,it can be purified to prepare carbohydrate vaccines,which have been widely used in the prevention of many infectious diseases.For example,capsular polysaccharides related components of Meningococci,Streptococcus pneumoniae,Haemophilus influenzae and others have been successfully prepared into carbohydrate vaccine and commercialized.The group B Streptococcus serotype ? concerned in this thesis is one of the pathogenic subtypes of group B Streptococcus,which can cause neonatal bacteremia and meningitis and other diseases,and can also cause pregnant women,the elderly and immunocompromised adults to suffer from endocarditis and meningitis.At present,there are few studies about this serotype,but its infection rate is increasing year by year.Based on the above,we designed and synthesized two tetrasaccharide glycosides of group B Streptococcus serotype ? with different glycosyl structure sequence by chemical method,which laid a material foundation for the follow-up study of structure-activity relationship,biological activity and related sugar vaccine development.This thesis mainly includes the following two parts:Chapter 1 briefly summarized the progress of group B Streptococcus vaccine development.Moreover,the chemical synthesis of group B Streptococcus serotype ? CPS-related oligosaccharides was also reviewed.In chapter 2,chemical synthesis of capsular polysaccharide related oligosaccharides of group B Streptococcus serotype ? was described.To synthesize the target tetrasaccharides,we first choose D-glucose,L-rhamnose and other monosaccharide as strating materials to synthesize various monosaccharide modules.In the synthesis of GBS-1 target molecule,the glycosylation strategy of[2+2]was adopted.Monosaccharide GBS-9 and GBS-5 was coupled to obtain the important disaccharide intermediate GBS-10,in which the newly formed ?-rhamnose glycoside bond was constructed using the hydrogen-bond-mediated aglycone delivery.Then,the C-3 picolinyl protecting group of rhamnose residue in GBS-10 was replaced with acetyl and the C-4 allyl protecting group was removed to obtain the disaccharide receptor GBS-12.Meanwhile,monosaccharide GBS-14 and GBS-13 are glycosylated to obtain the disaccharide donor GBS-15,which was then glycosylated with the disaccharide acceptor GBS-12 followed by deprotection to give the target tetrasaccharide GBS-1.In the synthesis of GBS-2 target molecule,we encountered some difficulties.After several attempts,we finally adopted the strategy of[1+2+1]to complete the target synthesis.The glycosylation of monosaccharide GBS-14 and GBS-24,followed by chloroacetyl protection,and then repeated glycosylation with monosaccharide acceptor GBS-22 to produce trisaccharide GBS-29.Finally,the target tetrasaccharide GBS-2 was obtained by glycosylation of trisaccharide GBS-29 and monosaccharide GBS-23,and then deprotection.The structures of the syntetic tetrasaccharides were well confirmed by NMR and MS spectra.