5-Thio-pyranoses

A. Fleetwood and V. Hughes, Convenient synthesis of 2,3-0-isopropylidene-5-thio-D-ribose and 5-thio-D-ribose synthesis of l,4-anhydro-2,3-0-isopropylidene-u-D-ribo-pyranose and l,4-anhydro-2,3-0-isopropylidene-5-thio-u-D-ribopyranose, Carhohydr. Res., 317 (1999) 204-209. 

Thiohydrogenolysis with Raney nickel has been used as a tool in the elucidation of structures of organic compounds. The technique has been used in establishing the configuration of streptose (146), the pyranose structure of ethyl-l-thio-a-d-mannoside (147) and the structure of tetraacetylpolygalitol (148). 

The reaction of 5-amino-5-deoxy-l,2-0-isopropylidene-a-D-xylo-furanose (15) with methanolic hydrogen chloride (0.5 %), under careful exclusion of moisture, results in a mixture of the anomers of methyl 5-amino-5-deoxy-D-xylofuranoside, from which the /8-D anomer crystallizes. The five-membered ring-structure was proved by the results of periodate oxidation and by the infrared spectrum of the tetraacetate, which shows a band for NH. A methyl pyranoside was not found, and 3-pyridinol (21) was formed only in traces. A spontaneous ring-enlargement, such as is observed under similar conditions with 1,2-O-isopropylidene-5-thio-a-D-xylofuranose (see p. 208), is not possible in this instance. Stabilization as the methyl fiiranoside is, apparently, so rapid that the secondary reaction (leading to the pyranose form) does not occur. If water (several percent) is added to the reaction mixture, glycoside formation is hindered, and a large proportion of 3-pyridinol is formed. ... 

Prediction of the composition of the equilibrium mixture on the basis of presumed conformational stability or instability is uncertain, as is shown by the example of 2,5-bis(acetamido)-2,5-dideoxy-D-xylose, obtainable by periodate cleavage of 3,6-bis(acetamido)-3,6-dideoxy-D-gulopyranose. From the reaction mixture, 2,5-bis(acet-amido)-2,5-dideoxy-D-xylofuranose can be obtained crystalline in 36% yield no report was made as to any content of pyranose. Other 5-acetamido-5-deoxyxylose derivatives, for example, methyl 3,5-bis(acetamido)-2-S-benzyl-3,5-dideoxy-2-thio-/3-D-xylofuranoside," were not susceptible to hydrolysis. ... 

Acetylation of the pyranose 227 gives crystalline tetra-O-acetyl-5-thio-/3-D-ribopyranose and the syrupy a-D anomer. Both compounds lack S-acetyl bands in their infrared spectra. Treatment of 227 with methanolic hydrogen chloride furnishes a mixture of anomeric methyl 5-thio-D-ribopyranosides which cocrystallize. Pure anomers are obtained on separation of the glycosides by use of a basic ion-exchange resin, or by separation of the triacetates on silica gel. The sulfur-containing, six-membered ring was established by periodate assay. 

At room temperature, 247 very rapidly shows an uptake of iodine corresponding to the complete oxidation of one thiol group. The oxidation product, the dimeric pyranose 249, is also formed by air oxidation of 247 on long standing of solutions thereof. Obviously, there exists, in addition to the favored thiofuranose form 247, a small proportion of the pyranose form 250 as an equilibrium component, and this has an easily oxidizable thiol group. By oxidation to the disulfide 249, this minor component of the equilibrium mixture is removed and, on rapid reattainment of the equilibrium, all of 247 becomes oxidized. The ready oxidizability of the thiol group of a 4-thiopyranose is likewise shown by the formation of bis(methyl 4-deoxy- 8-D-ribopyranoside-4-yl) 4,4 -disulfide by the air oxidation (iodine-catalyzed) of methyl 4-thio-)8-D-ribopyranoside. ... 

A synthesis of 4,5-dithio-L-xylose, a thio sugar in which the competition between sulfur-containing furanose and pyranose rings could be studied, has not yet been successful. Periodate scission of 3,4-0-isopropylidene-l,2-dithio-l,2-(thiocarbonyl)-D-glucitol led to an aldehyde which could not be isolated in pure form. ... 

A sulfur-containing, septanose form is only obtainable as a result of the protection of the C-5 and C-4 hydroxyl groups in such a way that the pyranose or furanose rings cannot be formed. 2,3,4,5-Tetra-O-acetyl-S-acetyl-6-thio-D-galactose diethyl dithioacetal (273), obtained from the corresponding 6-p-toluenesulfonate with potassium thioacet-ate, undergoes hydrolysis in the presence of mercuric chloride and... 

In the realm of thiosugars, the only pyranose known to be a natural product is 5-thio-D-mannose 7 (Figure 9.2), but more complex structures, salacinol 8 and cotalanol 9, have recently been found in plants known for their antidiabetic properties in Indian folk medicine. 

Stereocontrolled lincomycin was synthesized from methyl - D galactopyranoside, I, of methyl thio -lincosa - minide, II, using the direct synthesis precursor to lincomycin (5). The off - pyranose stereocenters C - 6 and C - 7 were controlled by an intramolecular nitrogen delivery reaction using epoxy alcohol. 

Thio-D-fructofuranose (88) was prepared from 5-(9-tosyl-l,3-(9-isopropylidcnc-o -L-sorbopyranose (87) by the standard sequence of reactions shown in Scheme 26. The H and C NMR spectra of 88 in aqueous solution show only tlie signals of the furanose a and p anomers in the ratio of 11 89, whereas tlie NMR spectra of D-fructose in D2O show the presence of the -pyranose, -furanose, a-furanose, and a-pyranose in the ratio of 6 3 1 trace, respectively. Partial hydrolysis or methanolysis of 90, prepared from 1,6-di-O-tosyl-D-fructofuranose (89), gave 3,6-anhydro-l-deoxy-6-thio-D-oraZ)W7o (or D-yv/o)-hexulose (91). Nucleophilic attack of the ring sulfur atom on C-3... 

Thioaldoses can form hemiacetal seven-membered septanose rings, provided that C-5 and C-4 hydroxyl groups are protected to avoid the fonuation of the more favorable furanose and pyranose rings. Thus, acid hydrolysis of 446 gave 2,3,4,5-tetra-O-methyl-6-thio-D-galactoseptanose (447) and ethanolysis afforded an anomeric mixture of the ethyl thioseptanosides 448. The isomerization to... 

Many derivatives of the dianhydro compounds have been prepared analogously. Thus, such substituted 1,6 2,3-dianhydro-/3-D-manno-pyranose (117) derivatives as the 4-O-alkyl,52,155,442,479,499,504-506,632,635 4-azido-4-deoxy,537,740,741 4-deoxy-4-fluoro,448,629 4-S-benzyl-4-thio,443 and 4-deoxy742 (compare Ref. 329) were prepared from the corresponding 2-sulfonates, and similar derivatives of l,6 3,4-dianhydro-/3-D-galactopyranose380,384,507,520,537,629,878,741 (compare Ref. 329) (119) and 1,6 3,4-dianhydro-R-D-allopyranose155,384 (32) were also prepared. 

The acetolysis of 3,6-di-0-acetyl-5-(S-acetyl-l,2-0-isopropylidene-5-thio-D-glucofuranose (352) afforded the pyranose thio sugar (353), and... 

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