1- thioglycoses

The most widely used synthons for the synthesis of thiooligosaccharides are the 1-thioglycoses and their synthesis has been widely studied. Approaches for the synthesis of 1,2-tra -thioglycoses include nucleophilic sulfur substitutions at the anomeric center of the glycosyl halides with either pscwdo-thiourea derivatives or other thionucleophiles [9, 10]. More recently, phase-transfer catalysis [11] and mild Lewis acid catalysed glycosidation of peracetylated sugars with thioacetic acid [12] have been applied. 

---

The most utilized synthons for the synthesis of thiooligosaccharides have been the per-acetylated 1-thioglycoses they have to be selectively deacetylated and... 

Glycosyl halides (7a-e) were stereoselectively transformed into l,2-tra s-thio-glycoses by i) (8a-d, 8j) a two-step procedure via the pseudothiourea derivatives [9,10a] the substitution of halide by thiourea is mostly a S l-type reaction since acetylated 1-thio-a-D-mannose (8b) was obtained from acetobromoman-nose (7b) [9cj ii) (8e-i) using thiolates in protic and aprotic solvents [10], or under phase transfer catalysis conditions [11]. Another approach involved the reaction of thioacetic acid with 1,2-trans-per-O-acetylated glycoses catalyzed with zirconium chloride [12]. The 1,2-trans-peracetylated 1-thioglycoses (8e-h) were obtained in high yield. No anomerized products could be detected in these reactions (Fig. 1). 

The first syntheses of 1,2-cfs-thioglycoses (a-D-gluco- and )3-D-manno- derivatives) have been achieved by the reaction in acetone of alkyl or benzyl xanthate or potassium thioacetate with the corresponding l,2-tra s-glycosyl halides [13]. More recently, tetra-O-acetyl-l-S-acetyl-l-thio-a-D-glucopyranose (10a) (Scheme 3) has been obtained i) by reaction of -acetochloroglucose (9 a) with either potassium thioacetate in HMPA or the tetrabutylammonium salt of thio-acetic acid in toluene [14] ii) by peroxide-induced addition of thioacetic acid to the pseudo-glucal (11) [15]. 

Several methods were described for the selective de-S-acetylation of 0-acetyl protected 1-thioglycoses. Sodium methoxide in methanol at low temperature (below -20 °C) was known to afford mainly the de-S-acetylated compound [16] or exclusively this compound when the reaction was quenched at low temperature by adding H-l- resin [17]. Demercuration of tetra-O-acetyl-l-phenylmercury(II)-thio- -D-glucopyranose (12) (Scheme 4) obtained by treatment of (8e) with phenylmercury(II)acetate afforded a convenient synthesis of tetra-0-acetyl-l-thio-/3-D-glucose (8a) [18]. This sequence applied to the a-anomer (10a) (Scheme 3) led to the expected de-S-acetylated compound (10b) [19]. Chemoselective deprotection of thioacetate at the anomeric position of peracetylated 1-thioglycoses was also achieved in good yield by action of cysteamine in acetonitrile or hydrazinium acetate in DMF [20,11]. 

The branched cyclodextrins (CDs, 17 a, 17 b) and their analogues with D-galactosyl and a-D-mannosyl residues (17c, 17d) have also been prepared under mild conditions by the approach depicted in Scheme 6 [24,25]. Selective in situ S-deacetylation and activation was obtained by treatment of peracetylated 1-thioglycoses (10a, 8e, 8g) by cysteamine in the presence of diAioerythritol in HMPA [26]. This method was very efficient for ffie synthesis of branched CDs (17a) (80%), (17b) (60%), and (17c) (85%) when the acceptor molecule (15b) bearing primary iodide was used. However, peracetylated 1-thioa-D-mannose (8f) failed as a donor under these conditions, but tetra-O-acetyl-l-thio-a-mannose (8 b) afforded the expected CD (17d) in high yield (83%). 

However the most efficient and reliable procedure involved the Sn2 displacement of a triflate group at C-4 of the acceptor with activated 1-thioglycoses. 

The first reported synthesis of peracetylated 1-thio-a-D-glucopyranose started from the Brigl s anhydride [9] but traditionally, 1,2-cw-thioglycoses have been generated from the 1,2-tranj-glycosyl halides by reaction of alkyl or benzyl xanthates in acetone [13], potassium thioacetate in hexamethylphosphoramide (HMPA) [14], or the tetrabutylammonium salt of thioacetic acid in toluene [15] (Scheme 1). A recent alternative is the peroxide-induced addition of thioacetic acid to hydroxy-glucal derivatives [16]. 

The most widely used synthons for the preparation of thiooligosaccharides have been peracetylated 1-thioglycoses, which can be selectively deprotected either in a two step procedure or in situ and used as an activated species (Scheme 3). 

There are several methods for the selective S-deacetylation of thioglycoses one of the most successful of these is demercuration of phenylmercury thio-a- or -P-D-glycoses [22, 23]. Deprotection has also been achieved by use of sodium methoxide... 

---