Aldoses 6-thio

Development of (Z, )-5-(2-methyl-3-phenyl-2-propenylidene)4-oxo-2-thio-xothiazolidine-3-acetic acid (Epalrestat, Kinedak), an aldose reductase inhibitor 97YGK651. 

Replacement of a hydroxy oxygen atom of an aldose or ketose, or of the oxygen atom of the carbonyl group of the acyclic form of an aldose or ketose, by sulfur is indicated by placing the prefix thio , preceded by the appropriate locant, before the systematic or trivial name of the aldose or ketose. 

Fischer420 reported the preparation of mercaptals from carbohydrates the reaction can be applied to all aldoses and aliphatic thiols, but fails with thio-phenols and also with fructose and sorbose,421 so that it can be used to separate, e.g., glucose from a mixture with fructose and sorbose. 

In this Section, the naturally occurring 1-thio-D-glucosides are discussed first. Chemically synthesized 1-thioglycosides and their reactions are then considered. Other iS-substituted derivatives of the 1-thio sugars, which normally react by cleavage of the /S-substituent to give the free 1-thio-aldoses, are treated in Section III (p. 152). 

L-arabinose. A paper-chromatographic study of the mercaptalation reaction with n-galactose, D-glucose, and D-mannose confirmed that almost complete conversion to the dithioacetal occurred within 5 minutes, but, after several hours, an equilibrium was set up in which two 1-thio-glycosides, probably the anomeric pyranosides, the dithioacetal, and the free aldose were all present the 1-thioglycoside was particularly favored with the D-mannose structure. 3-Amino-3-deoxy-D-mannose reacted (qualitatively) similarly to D-mannose, but more slowly, probably because of the polar influence of the amino group. 

Displacements Catalyzed by Adds.—The acid-catalyzed mercaptala-tion reaction with ethanethiol normally leads to the aldose diethyl dithio-acetal, but, in anhydrous reaction media, further ethylthio substituents may be introduced into the molecule, usually at C-2. Brigl and coworkers found that ethanethiol and hydrogen chloride convert 3,4,5,6-tetra-O-benzoyl-D-glucose diethyl dithioacetal into 3,4,5,6-tetra-O-benz-oyl-2-)S-ethyl-2-thio-D-glucose (mannose) diethyl dithioacetal. The diethyl... 

Aldoses containing acetamido-, amino-, deoxy-, and thio-groups have been examined by g.l.c. of their peracetylated aldononitrile derivatives. Chemical... 

Several 4-thio-D-glucofuranosylamine disaccharide derivatives such as 8 (a p, 1 3) were obtained by direct condensation of 4-thio-D-glucose with an amino-sugar. A review of the application of palladium si-allyl complexes of unsaturated carbohydrates in fuctionalization at the anomeric centre included the use of 7V-nucleophiles to provide unsaturated JV-glycosyl derivatives. Cyclic l,2-iV,0-phosphate derivatives of aldoses feature as intermediates in selective 2-0-phosphorylation reactions (see Chapter 7). 

Reduction of the sugar acid lactones to aldose sugars also may be accomplished by catalytic hydrogenation (I40) or, very conveniently, with sodium borohydride in aqueous solution ) Other methods of reduction include the catalytic hydrogenation of the acetylated aldonyl chlorides (14 ) or thio esters (I4S). 

---