Polytetrafluoroethylene Particles Assist In The Synthesis Of Oligosaccharides Supported By Fluorine Carriers And The Synthesis Of Kdo Derivatives

Carbohydrates,one of the three natural biomacromolecules,are indispensible component of organism.They play important roles in life process and are closely related to the formation and development of many diseases.However,Research in carbohydrates have been greatly delayed and the understanding of their roles have been limited due to the scarce source of structurally defined oligosaccharides.Chmical synthesis,one of the powerful tools for preparation of carbohydrates,has made great contributions to the source of oligosaccharide and glycoconjugate.Owing to the multiple hydroxyl groups in carbohydrates,the stereoselectivity in glycosylation and tedious purification process during the synthesis of carbohydrates,it's still challenging to chemically synthesize carbohydrates efficiently.In this thesis,studies have been focused on two major topics:"polytetrafluoroethylene particle-assisted syntheses of oligosaccharides with fluorous tag" and "studies toward the syntheses of Kdo derivatives".To simplify the purification process and improve synthetic efficiency of oligosaccharides,we proposed a new strategy "solution-phase syntheses,solid-phase seperation" by mimicking automated syntheses,the followings have been done in the first part work.1)Three benzyl type fluorous tags with two fluorous side chains were synthesized.In addition,deprotection of fluorous tag tethered carbohydrates and regeneration of the fluorous tags were carried out.2)A new protocol to synthesize oligosaccharides was developed.During the process of each glycosylation circle,polytetrafluoroethylene particles(ptfe particles)were added into reaction mixture(Alternatively,the ptfe particles can be added after the reaction is complete),and then the coupling or deprotection reaction proceeded in a traditional solution-phase way.After the reactions iscomplete,the low boiling solvent was removed under reduced pressure and then fluorousphobic solvent was added into the reaction mixture.The mixture was allowed to stir,and the nonfluorous compounds and reagent were separated from fluorous-tagged product by simple filtration.Latter,the fluorous-tagged product was released by adding common organic solvent.Thus,pure product can be afforded just by filtration.The strategy has both advantages of solution-phase reaction and solid-phase synthesis of oligosaccharides:a)The reaction can be monitored by traditional methods such as TLC,NMR and MS;b)Simple and rapid purification processs.The use of fluorous solvent in F-LLE and tedious transfer process in F-SPE was avoided;c)Ptfe particles are stable enough under normal conditions for glycosylation and deprotection in carbohydrate chemistry.3)The above-mentioned fluorous tags and protocol were applied to study for the syntheses of ?(1?2)-mannosyl oligosaccharides.4)Studies toward the syntheses of tumor-associated carbohydrate antigens Globo H and its derivatives were done by the same strategy.At last,globol deprotection can be completed using catalytic hydrogenation to afford Gb3 and Globo H.The second part work is involved with "studies toward the syntheses of Kdo derivatives".The following are the major topics of this part.1)Starting from D-mannose,the protected Kdo ester(compound 3.4 in this thesis)was prepared in tree steps and more than 70%yield.2)With compound 3.4 in hand,many different methods were explored to synthesize 2-deoxy-?-Kdo ester and the ester could be prepared with 10 g scale by the epimerization of the ?-isomer in 85-90%yield.3)Other Kdo derivatives which play important roles in the syntheses of Kdo-containing oligasacchrides or possess important biological activity were prepared,such as Kdo glycal,2-deoxy-?-Kdo,2-deoxy-?-Kdoammonium salt,8-N3(or NH2)-2,8-di-deoxy-?-Kdo.Furthermore,the formation mechanisms of some interesting products were studied.