117253-02-8Relevant academic research and scientific papers
A convergent strategy for the preparation of N-glycan core di-, tri-, and pentasaccharide thioaldoses for the site-specific glycosylation of peptides and proteins bearing free cysteines
Watt, Gregory M.,Boons, Geert-Jan
, p. 181 - 193 (2007/10/03)
Mammalian glycoprotein biosynthesis produces heterogeneous ranges of proteins that possess the same peptide backbone but differ in the nature and site of glycosylation. This feature has frustrated efforts to develop therapeutic glycoproteins as well as the elucidation of biological functions of individual glycoforms. We have developed an attractive approach to well-defined glycoforms of glycoproteins by oxidative coupling of thioaldoses to cysteine-containing peptides and proteins to give disulfide-linked neoglycoconjugates. To this end, the chemical synthesis di-, tri-, and pentasaccharide N-glycan thioaldoses was undertaken. A convergent approach was used for the preparation of the pentasaccharide containing a 'synthetically difficult' β-mannoside linkage. This linkage was installed by forming initially the corresponding β-glucoside-containing pentasaccharide, followed by inversion of configuration at C-2. This approach exploited a levulonyl ester at C-2 of a glucosyl donor, which directed the coupling to give the β-glucoside exclusively and could be removed selectively using hydrazine acetate without affecting other base-labile functionalities. The resulting alcohol was converted into a triflate, which was displaced by tri-n-butylammonium acetate to give a β-mannosidic linkage. The trisaccharide N-glycan was prepared in a similar manner. Thioaldoses were prepared by displacing the peracetylated α-glycosyl chlorides with thioacetate to give the peracetylated β-thioacetates, which upon saponification gave the desired compounds. The incubation of molar excesses of chitobiose thioaldose with cysteine-containing glutathione and BSA resulted in the site-specific formation of a disulfide-linked neoglycopeptide and neoglycoprotein, respectively.
2-(Trimethylsilyl)ethyl Glycosides. Synthesis, Anomeric Deblocking, and Transformation into 1,2-Trans 1-O-Acyl Sugars
Jansson, Karl,Ahlfors, Stefan,Frejd, Torbjoern,Kihlberg, Jan,Magnusson, Goeran,et al.
, p. 5629 - 5647 (2007/10/02)
Twenty-seven mono --> tetrasaccharidic 2-(trimethylsilyl)ethyl (TMSET) glycosides were synthesized by the Koenigs-Knorr-type method in combination with a wide range of standard reagents for glycoside synthesis and protecting-group chemistry.Variously protected TMSET glycosides were treated with BF3*Et2O (0.7-0.8 equiv) and different carboxylic anhydrides (1.1-15 equiv) in toluene at 22-55 deg C, which gave in one step the corresponding protected 1-O-acyl sugars.In the majority of cases, the yields of purified compounds exceeded 90percent and the anomeric configuration of the starting TMSET glyoside was conserved to a large extent (>95percent) in most of the 1-O-acylated products.Unprotected and acetyl-, benzoyl-, benzyl-, dimethyl-tert-butylsilyl-, and phthaloyl-protected mono-->tetrasaccharidic TMSET glycosides were anomerically deblocked by using trifluoroacetic acid in dichloromethane at 0-22 deg C for 10-30 min.The hemiacetal products were isolated in 88-96percent yield; all reagents and byproducts were volatile and easily removed.
