Thioglycoside method

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. 

D. Horton, 1-Thioglycosides, Methods Carbohydr. Chem., 2 (1963) 368-373 and references therein. 

Branched Homotetrasaccharides.-p-D-Glcp-(l- 6)-[p-D-Glc/)-(l->3)]-P-D-Glcp-(l->6)-a-D-Glc/7-OMe has been prepared by use of ethyl thioglycoside methods in connection with phytoalexin elicitor studies. ... 

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. 

Nicolaou and coworkers reported a new method for preparing glyco-syl fluorides (38) from phenyl thioglycosides (37) by treatment with di-ethylaminosulfur trifluoride (DAST)-A -bromosuccinimide (NBS), or HF-pyridine-NBS, the phenylthio group of the thioglycosides being initially activated by NBS. Thus prepared were compounds 39, 40, and 42 (see Table I) and 3,4-C)-carbonyl-2,6-dideoxy-3-C-methyl-L-n Z)ohexo-pyranosyl, 2-azido-2,6-dideoxy-3,4-0-isopropylidene-D-altropyranosyl,... 

Wong and coworkers showed that 5-azido sialyl donors protected with O-acetyl ester are useful for a-selective glycosylations of primary hydroxyls (Scheme 4.6e) [169]. It was proposed that the linear and electron-withdrawing nature of the C-5 azido moiety stabilizes the reactive axial acetonitrile adduct to allow the incoming nucleophile to approach the a-face in an SN2-like fashion. In addition, a chemose-lective glycosylation method has been developed for the synthesis of NeuAca-(2 —> 9) NeuAc as thioglycoside donor for use in the subsequent glycosylations [169]. 

The sulfoxide method has been applied to the concept [319,374] of intramolecular aglycone delivery for the formation of [1-mannosidcs by means of a silylene linker. In the original work, the acceptor and a thioglycoside donor were joined by means of a silylene group before the oxidation to the sulfoxide [141]. However, it was later found that the preformed sulfoxide was tolerated by the chemistry for the introduction of the linker [286,375]. The intramolecular aglycone delivery step was shown to function effectively for the transfer of the donor to the 2-, 3- and 6-position of glucopyr-anosides, as exemplified in Scheme 4.64. 

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