Reagent controlled stereoselective synthesis of 1,2-cis-glucoside

Session: 
S5.3 Oligosaccharide synthesis II
Code: 
OL5.3.2
Location (hall): 
Galactose
Start/end time: 
Tuesday, July 2, 2019 - 15:00 to 15:15
Liming
Wang

Liming Wang1, Herman Overkleeft1, Gijsbert van der Marel1, Jeroen Codée1

1Leiden Institute Of Chemistry, Leiden University, Leiden, The Netherlands

The development of a general glycosylation method that allows for the stereoselective construction of glycosidic linkages is a tremendous challenge. Because of the differences in steric and electronic properties of the building blocks used the outcome of a glycosylation reaction can greatly vary when switching form one glycosyl donor-acceptor pair to another. We developed a strategy to install cis-glucosidic linkages in a fully stereoselective fashion that is under direct control of the reagents used to activate a singly type of donor building block. The activating reagents are tuned to the intrinsic reactivity of the acceptor alcohol to match the reactivity of the glycosylating agent with the reactivity of the incoming nucleophile. A protecting group strategy is introduced that is based on the sole use of benzyl-ether type protecting groups to circumvent changes in reactivity as a result of the protecting groups. For the stereoselective construction of the α-glucosyl linkages to a secondary alcohol, a per-benzylated glucosyl imidate donor is activated with a combination of trimethylsilyltriflate and formamide (DMF or N-methyl-N-phenylformamide), while activation of the same imidate donor with trimethylsilyl iodide in the presence of triphenylphospine oxide allows for the stereoselective cis-glucosylation of primary alcohols. The effectiveness of the strategy is illustrated in the modular synthesis of a linear 1,6- 1,4-, 1,3- and 1,2-linked oligoglucosides as well as α-linked glucosamines, present Mycobacterium tuberculosis, Aspergillus fumigatus and Enterococcus faecalis derived antigenic carbohydrates.

Figure 1. 1,2-cis-oligosaccharides and proposed glycosylation mechanism

References: 
  1. L. Wang, H. S. Overkleeft, G. A. van der Marel, J. D. C. Codée, J. Am. Chem. Soc. 2018, 140, 4632-4638.
  2. L. Wang, H. S. Overkleeft, G. A. van der Marel, J. D. C. Codée*, Eur. J. Org. Chem 2018, DOI: 10.1002/ejoc.201800894.
  3. Lu, S. R.; Lai, Y. H.; Chen, J. H.; Liu, C. Y.; Mong, K. K. T. Angew. Chem. Int. Ed. 2011, 50, 7315-7320.
  4. Mukaiyama, T.; Kobashi, Y. Chem. Lett. 2004, 33, 1.

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