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Development of Novel Glycosylation Reaction Using Odorless Benzenethiols

使用无味苯硫醇开发新型糖基化反应

基本信息

批准号：
20590022
负责人：
KAJIMOTO Tetsuya
金额：
$ 3.08万
依托单位：
Suzuka University of Medical Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

项目摘要

p-Octyloxybenzenethiol (1) was first synthesized as a new odorless benzenethiol. Using 1, 1-(p-octyloxy)phenyl-thio-glycosides (2) were prepared as a new type of glycosyl donors in the glycosylation reaction. After trying the glycosylation reactions under several conditions, it was found that 2 were excellent glycosyl donors in glycosylation reaction activated with N-iodosuccinimide and triflic acid. All the procedure from the preparation of 2 to the glycosylation reaction could be attained completely under conditions where no malodorous stench was generated.Next, another glycosylation reaction was performed using a combination of 2 and 1-(p-octyloxy)phenyl glycosyl sulfoxides (3), which were prepared by the oxidation of 2, as a glycosyl donor and an acceptor, respectively. Promising results were obtained when p-octyloxylphenyl N-phthalimido-D-thio-glucosaminide derivative was activated with NIS and TfOH for the glycosylation of 3 carrying a free hydroxyl group, especially, at the C-6 position. Successive reduction of the resulting disaccharyl sulfoxides with Ph_3P/CBr_4/CH_3CN provided the corresponding thio-glycosides, which could be used as the glycosyl donors in a following glycosylation reaction to afford trisaccharides in good yield. Using the present method, 4-iodo-phenylalkyl ss-D-N-acetylglucosaminyl-(1-2)-ss-D- mannopyranosyl(1-6)-α-D-glucopyranoside (4), which was designed as a monitoring glycoconjugate for the activity of malignant tumor specific N-acetyl-D-glucosaminyltransferase-V.Finally, it is noteworthy that the glycosylation reaction using a combination of 2 and 3, which was developed in the present study, provided a novel and useful synthetic method of oligosaccharides, i. e., the glycosylation reaction from the non-reducing ends.

对辛氧基苯硫醇(1)是一种新型无臭苯硫醇。利用1,1 -（对辛氧基）苯基硫代糖苷(2)作为糖基化反应的新型糖基供体。通过对不同条件下糖基化反应的尝试，发现在n -碘琥珀酰亚胺和三酸活化的糖基化反应中，2是很好的糖基供体。从2的制备到糖基化反应的所有过程都可以在不产生恶臭的条件下完全完成。接下来，使用2和1-（对辛基氧基）苯基糖基亚砜(3)的组合进行另一个糖基化反应，它们分别作为糖基供体和受体，由2氧化制备。用NIS和TfOH活化对辛氧基苯基n -邻苯二胺- d -硫代氨基葡萄糖衍生物，使携带一个游离羟基的3糖基化，特别是在C-6位置，得到了令人满意的结果。用Ph_3P/CBr_4/CH_3CN连续还原得到相应的硫代糖苷，这些硫代糖苷可作为糖基供体在随后的糖基化反应中得到产率较高的三糖。本方法设计了4-碘苯基烷基-ss- d - n -乙酰氨基葡萄糖-(1-2)-ss- d -甘露吡喃基(1-6)-α- d -葡萄糖吡喃苷(4)作为恶性肿瘤特异性n -乙酰- d -葡萄糖氨基转移酶v活性监测糖缀合物。最后，值得注意的是，本研究发展的2和3结合的糖基化反应，为低聚糖的合成提供了一种新颖而有用的方法，即非还原端糖基化反应。