Thioglycoside

A central theme of carbohydrate chemistry today is the construction of oligosaccharides as they are found in glycoproteins (H. Paulsen, 1990). Three closely related methods have proven to be reliable in complex syntheses, namely the halide, imidate, and thioglycoside methods. 

Thioglycosides can be activated for gfycosylation reactions with sulfur electrophiles, e.g., with dimethyl(methylthio)sulfonium triflate or with methanesulfenyi bromide and silver(l +) to form reactive sulfonium intermediates (F. Dasgupta, 1988). 

In contrast, cleavage of alkyl and also aryl thioglycosides with dimethyl(meth-ylthio)sulfonium tetrafluoroborate takes place with total inversion of configuration [9] (equation 12) The latter reagent is commercially available or easily prepared as a crystalline nonhygroscopic solid [10]. All the three above-mentioned reagents... 

Names are formed analogously to those for thioglycosides (2-Carb-33.3). Examples ... 

III. Conversion of Thioglycosides Into Other Glycosyl Donors. 183... 

IV. In situ Generation of Glycosyl Halides from Thioglycosides. 184... 

Transfer of the Armed-Disarmed Concept to Thioglycoside Glycosylation... 

In the Koenigs-Knorr method and in the Helferich or Zemplen modifications thereof, a glycosyl halide (bromide or chloride iodides can be produced in situ by the addition of tetraalkylammonium iodide) is allowed to react with a hydrox-ylic compound in the presence of a heavy-metal promoter such as silver oxide, carbonate, perchlorate, or mercuric bromide and/or oxide,19-21 or by silver triflu-oromethanesulfonate22 (AgOTf). Related to this is the use of glycosyl fluoride donors,23 which normally are prepared from thioglycosides.24... 

These methods arc summarized in Scheme 1. Methods based on the use of thioglycosides are covered later in this chapter. 

A great variety of methods for the preparation of alkyl and aryl 1-thioglycosides of aldoses have been described30-31 ... 

Fully acetylated hexopyranoses react with thiols in the presence of Lewis acids, such as BF3-Et20.32,33 The reaction is faster with 1,2-trans acetates than with the corresponding 1,2-cij ones and 1,2-trans products predominate. Alkyl, alkenyl, and aryl thioglycosides are produced by this method. Variations on this method include the use of trimethylsilyl34 or stannyl derivatives35 of the thiols. 

In this classic41 and general method, an acylated glycosyl halide reacts with a thiolate anion to produce a 1-thioglycoside, usually with 1,2-trans configuration. With alkyl thiolates, re-acylation is normally required following this treatment. 

Partial hydrolysis of dithioacetals has been found useful for the preparation of anomers not obtained by the foregoing methods and also for preparation of fu-ranosidic 1-thioglycosides. 

This preparation, specifically of acylated aryl thioglycosides, is carried out by reaction of, for instance, a 2,3,4,6-tetra-O-acety 1-1 -thio-P-D-glucopyranose with a di-azonium salt, followed by thermal decomposition of the intermediate diazo product. 

Acylated glycosyl thiocyanates are made by treatment of acylated glycopyranosyl halides with potassium thiocyanate.30 Reaction at —40° with a Grignard reagent affords alkyl or aryl 1-thioglycosides.54... 

Acetylated 1-thioaldoses react with alkenes in the presence of azobis(isobuty-ronitrile) (AIBN) to give acylated alkyl 1-thioglycosides.55... 

Tris(4-bromophenyl)ammoniumyl hexachloroantimonate (TBPA) differs from the other promoters in that its cation is a radical, and as such produces radical cationic sulfonium ions as glycosylating species from thioglycosides.85 The use of this promoter arose from earlier work on the electrochemical generation of 5-glycosyl radical cations as glycosylating species. 

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