Iterative oligosaccharide synthesis

A synthesis method and oligosaccharide technology, applied in the field of sugar chemistry, can solve the problems of unforeseen reaction process monitoring, hindering the development and difficulties of oligosaccharide solid-phase synthesis

Active Publication Date: 2008-11-12
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the unpredictability of the glycosylation reaction on a solid-phase support and the difficulty in monitoring the reaction process have greatly hindered the development of solid-phase synthesis of oligosaccharides.

Method used

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  • Iterative oligosaccharide synthesis
  • Iterative oligosaccharide synthesis
  • Iterative oligosaccharide synthesis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] At a temperature of -60°C, add 1 equivalent of p-toluenesulfur chloride (TolSCl) to the ether solution of active donor 1 and silver trifluoromethanesulfonate (AgOTf), and use AW300 molecular sieves as a dewatering agent. After the donor 1 is fully activated, the ether solution of the active donor / acceptor 4 is added, and the disaccharide 2 is obtained in a yield of 74%. The ratio of α and β isomers is 3.3:1 (Table 1, No. 1 ), the anomeric position of disaccharide 2 has a p-tolylthio group. Disaccharide 2 was glycosylated with donor / acceptor 4 to obtain trisaccharide 9 with a yield of 71% (No. 2). The hydroxyl group on the vertical bond of the active donor / acceptor 5 reacted with the donors 1 and 3 to form disaccharides 10 and 11, respectively, with a yield of 66% (No. 3 and 4).

[0068] p-Tolylthiotriflate (TolSOTf) is a strong activator capable of stoichiometrically activating an inactive donor. The inactive donor 6 can successfully react with the very active donor / a...

Embodiment 2

[0074] Figure 3. One-pot oligosaccharide synthesis

[0075]

[0076] To test the feasibility of an activity-independent one-pot method for multi-step glycosylation reactions, we synthesized several oligosaccharides by sequentially adding different building blocks in the same reaction vessel9,16,17 and 18 (Fig. 3). It is worth noting that the yield of trisaccharide 9 synthesized by the one-pot method is 66% (Fig. 3a), while the total yield of the stepwise synthesis is only 53% (Table 1, No. 1, 2). We used different structural modules 6, 4, 7, 19 to synthesize tetrasaccharide 16 by one-pot method, used structural modules 3, 5, 7, 20 to obtain tetrasaccharide 17, and used structural modules Sugar 18, the total yields were 68%, 55% and 48%, respectively. Therefore, the one-pot synthesis method not only saves the separation and purification of intermediates, but also improves the overall yield of the reaction through the reduction of purification steps. The final oligosacchar...

Embodiment 3

[0078] Figure 4

[0079]

[0080] In another example of the present invention, an affinity tag is introduced into the oligosaccharide to simplify the purification of the target oligosaccharide product (Figure 4).

[0081] The introduction of the affinity tag is generally by linking the glycosyl acceptor to the affinity tag through its reducing end. Any suitable affinity tag can be used in this process. In some examples of the invention, affinity tags can be attached to insoluble polymers. For example, azides (Figure 4) or ketones / aldehydes can be used as affinity tags. After the synthesis of oligosaccharides is completed, the insoluble polymer is added to the reaction solution to connect the oligosaccharides to the polymer. Any insoluble polymer suitable for attachment to oligosaccharides can be used, such as phosphine-containing polymers. The polymer can be added in any suitable manner. For example, after oligosaccharide synthesis is complete, the polymer can be added...

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Abstract

A process for synthesizing an oligosaccharide includes (a) activating a protected glycosyl donor with a promoter in the absence of a glycosyl acceptor to produce a reactive intermediate, the glycosyl donor having an activatable aglycon at the anomeric carbon; (b) adding a protected glycosyl donor / acceptor to the reactive intermediate to produce a new glycosyl donor, the glycosyl donor / acceptor having both an activatable aglycon at the anomeric carbon and a free hydroxyl group; (c) repeating steps (a) and (b) to add any additional protected glycosyl donor / acceptors; and (d) adding a protected glycosyl acceptor to produce the oligosaccharide, the glycosyl acceptor having a free hydroxyl group and a non-activatable aglycon at the anomeric carbon.

Description

technical field [0001] The invention relates to a method for synthesizing sugars, in particular to a method for synthesizing oligosaccharides, and belongs to the field of sugar chemistry. Background technique [0002] Sugar plays an important role in many physiological processes, such as immune response, inflammatory process, tumor metastasis and bacterial / viral infection, etc. However, the lack of general methods for the synthesis of oligosaccharides has greatly hindered the study of glycobiology. Over the past decade, liquid-phase one-pot synthesis and solid-phase synthesis methods of oligosaccharides have been developed. One-pot synthesis refers to the realization of several glycosylation coupling reactions in the same reaction vessel without the isolation of intermediates. The current one-pot synthesis method is mainly achieved by sequentially adding the glycosyl structural modules in the order of anomeric activity from large to small (Fig. 1a). The activity of the st...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07H3/06C07H5/04C08B37/00G01N33/53
CPCC07H5/04
Inventor 黄雪飞叶新山
Owner PEKING UNIV
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