Studies toward Rapid Synthesis of Oligosaccharides on Solid Phase

寡糖及其复合物的固相合成是研究其生物学功能的重要手段。糖苷化反应是寡糖固相合成的重要环节。因此，我们开发了新的和有效的糖苷化方法与硫代糖苷的NBS和强酸盐的组合，或通过使用高价碘试剂制备的PhIO-Lewis酸。我们还发现N-苯基硒代邻苯二甲酰亚胺（PhSeNPhth）-Mg（ClO_4）_2在温和条件下也能有效地促进硫代糖苷的糖苷化反应。由于用PhSeNPhth-Mg（ClO_4）_2进行的糖苷化反应在几乎中性的条件下进行，因此酸敏感的三苯甲基能够用作保护基。发现在供体的6-位上的三苯甲基显著增加α-选择性。通过使用在6-位具有三氯乙氧羰基（Troc）的苄基化供体也实现了高α-选择性。我们最近开发了对叠氮基间氯苄基（Cl-Azb），其对DDQ稳定，但在叠氮基转化为相应的亚氨基膦后，可容易地被2，3-二氯-5，6-二氰基苯醌（DDQ）氧化裂解。Cl-Azb在固相合成中表现出良好的性能。我们以前描述过对-酰氨基苄基比MPM基团具有更高的酸稳定性，但容易被DDQ裂解。因此，对-戊二酰氨基苯基官能团可以很容易地从对硝基苄基官能团衍生出来，并且可以很容易地被DDQ裂解。对-酰氨基苯基糖苷也可以用作连接体，其可以很容易地从对-乙酰氨基苯基糖苷中获得。硝基苯基糖苷，并且可以容易地通过硝酸铈（IV）铵（CAN）氧化裂解。

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.