Studies toward Rapid Synthesis of Oligosaccharides on Solid Phase

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Solid phase synthesis of oligosaccharides and glycoconjugates has been strongly required for the investigation of their biological functions. Glycosidation reaction is most important issue for the solid phase synthesis of oligosaccharides. We, therefore, developed novel and effective glycosidation methods with thioglycosides by combination of NBS and strong acid salts or by using hypervalent iodine reagents prepared from PhIO-Lewis acids. We also found that N-phenylselenophthalimide (PhSeNPhth) -Mg (ClO_4) _2 also effectively promotes glycosidation with thioglycosides under mild conditions. Since the glycosidation using PhSeNPhth-Mg (ClO_4) _2 proceeded under almost neutral conditions, acid-sensitive trityl group was able to use as a protecting group. Trityl group at 6-position of the donor was found to remarkably increase alpha-selectivity. High alpha-selectivity was also achieved by use of a benzylated donor possessing trichloroethoxycarbonyl (Troc) group at the 6-position.There have been only limited numbers of practical protecting groups of hydroxyl functions and linkers for solid phase synthesis of oligosaccharides. We recently developed p-azido-m-chlorobenzyl group (Cl-Azb) which is stable to DDQ but can be readily cleaved by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) oxidation after conversion of the azide group into the corresponding iminophosporane. Cl-Azb showed good performance for the solid phase synthesis.We previously described p-acylaminobenzyl groups have higher acid stability than the MPM group but are readily cleaved with DDQ.The p-glutarylaminophenyl function was thus developed as a linker which can be readily derived from p-nitrobenzyl function and can be easily cleaved by DDQ.The p-acylaminophenyl glycoside was also utilized as a linker which can be readily obtained from p-nitrophenyl glycoside and can be readily cleaved by ammonium cerium (IV) nitrate (CAN) oxidation.