Glucitol preparation

Amino-l,5-anhydro-6-deoxy-D-glucitol, prepared in standard reactions from D-glucose, has been used to prepare compounds (26)... 

Sugihara and Schmidt49 reported the isolation of 2,5-anhydro-D-glucitol in crystalline form its preparation on a relatively large scale has been described in the patent literature,50 and consists in the thermal dehydration of D-mannitol. The process leads to the formation of 1,4-anhydro-D-mannitol, 1,5-anhydro-D-mannitol, 1,4 3,6-dianhydro-D-mannitol, and 2,5-anhydro-D-glucitol, which is isolated as the crystalline 1,3-O-isopropyIidene derivative (35). 

The sugar alcohol anhydride polygalitol, 1,5-anhydro-D-glucitol, may be prepared from the root of Poly gala Senega L.49 The process is, however, a time-consuming one and chemical synthesis of the substance by Raney... 

Both L-gulose12,13 (9) and D-gulose (d-9, see Ref. 10) have been oxidized with bromine to L- or D-gulonic acid, respectively (see Scheme 1). L-Gulose (9) has been prepared by a number of different procedures. Schemes 2 and 3 show two early procedures that afforded L-gu-lose, but the overall yields were low (<30%). In the first procedure12 (see Scheme 2), D-glucitol (10) was converted into 2,4-O-benzylidene-D-glucitol (11), which was then oxidized with lead tetraacetate to 2,4-O-benzylidene-L-xylose (12). Nitromethane was added to 12 to afford crystalline 13 in 50% yield. Hydrolysis of 13 provided 14, which was treated with sodium hydroxide, followed by sulfuric acid, to afford 9, which was isolated in 52% yield as the 2-benzyl-2-phenylhydrazone. 

On the other hand, borohydride reduction of the ketose o-fructose will give a mixture of o-glucitol and its epimer, D-mannitol. A better approach to D-mannitol would be reduction of the aldose D-mannose. o-Glucitol (sorbitol) is found naturally in the ripe berries of the mountain ash (Sorbus aucuparia), but is prepared semi-synthetically from glucose. It is half as sweet as sucrose, is not absorbed orally, and is not readily metabolized in the body. It finds particular use as a sweetener for diabetic products. o-Mannitol also occurs naturally in manna, the exudate of the manna ash Fraxinus ornus. This material has similar characteristics to sorbitol, but is used principally as a diuretic. It is injected intravenously, is eliminated rapidly into the urine, and removes fluid by an osmotic effect. 

Examples of other fluorinated inhibitors, mainly of D-glucosidases, are the 2-deoxy-2-fluoro derivative 106 (Scheme 27) of miglitol (A-hydroxyethy I -1 -deoxynoj i i i my-cin, 107),229 4-deoxy-4,4-difluoroisofagomine (108),230 3-deoxy-3-fluoro-calystegin B2 (109),231 the 1-deoxyfluoro derivative (110) of 2,5-dideoxy-2,5-imino-D-mann-itol,232 as well as the 3-deoxyfluoro analogue (111) of nonnatural l-DMDP (2,5-dideoxy-2,5-imino-L-mannitol)233 and the 3-deoxy-3,3-difluoro derivative (112) of 2,5-dideoxy-2,5-imino-D-glucitol (113).234 All of these are weaker inhibitors than the parent compounds. l,4,6-Trideoxy-6-fluoro-l,4-imino-D-mannitol (114) was prepared by Winchester and coworkers.210... 

The configuration at C-2 was established by comparison with the optical activities of 1,5-anhydro-D-mannitol and -D-glucitol and the proton magnetic resonance (p.m.r.) spectra of their acetates.31(b) This reaction is useful for the preparation of C-2 substituted derivatives, but the configuration at C-2 of the products must then be established. 

The synthesis of an alditol having a 4-membered (oxetane) ring was first reported by Ustyuzhanin and coworkers,50 who prepared 1,3-anhydro-5,6-di-0-methyl-2,4-0-methylene-D-glucitol by saponification of the 1-p-toluenesulfonate of the corresponding derivative of D-... 

Oxepane (seven-membered) rings (1,6-anhydrohexitols)52 have been prepared from the 3,4-isopropylidene acetals of D-mannitol, D-glucitol, and L-iditol, by way of alkaline hydrolysis of the corresponding 1,2 5,6-dianhydrides. The ring structures of the products were established through periodate oxidation and lead tetraacetate oxidation the requisite amount of formic acid was produced, and 3 equivalents of lead tetraacetate were consumed. No inversions at any of the asymmetric centers were involved in the reactions conducted, so the oxepanes had retained the configurations of the starting hexitols. 

Isosorbide and isomannide are important by-products of the starch industry, arising from dehydration of D-sorbitol and D-mannitol. These commercial starting materials provide an easy and inexpensive access to optically pure functionalized tetrahydrofurans like 04,05-isopropylidene-1-iodo-3,6-anhydro-1-deoxy-D-glucitol and 04,05-isopropylidene-l-iodo-3,6-anhydro-1-deoxy-Q-mannitol. This procedure describes a preparation of the former compound and the epoxide derived therefrom. 

To the submitters knowledge, 04,05-isopropylidene-1-iodo-3,6-anhydro-1-deoxy-D-glucitol and 04,05-isopropylidene-1,2 3,6-dianhydro-D-glucitol have not been prepared before. However, the corresponding isomannide derivatives have been obtained in five steps from mannitol in low overall yield by Foster and Overend in 1951.6 7 The present method is a simple, rapid and inexpensive route to multigram amounts of these tetrahydrofuran derivatives in reasonable yields. 

The paradigmatic hexosaminidase inhibitor with basic nitrogen in the ring, 2-acetamido-1,2-dideoxynojirimycin (2-acetamido-l,2,5-trideoxy- 1,5-imino-D-glucitol, 33) has not been found naturally to date. This inhibitor was first prepared by Fleet and co-workers [76,77] in a 17-step synthesis from D-glucose via methyl 3-0-benzyl-2,6-dideoxy-2,6-imino-a-D-mannopyranoside together... 

They prepared 1,4 3,6-dianhydrides of D-mannitol, D-glucitol and L-iditol ... 

Adducts of alkali metal salts prepared in anhydrous alcoholic media generally retain very little alcohol of solvation after being dried under vacuum at room temperature (see Table I). The unusual ability of adducts of D-glucitol to retain alcohol is probably due largely to the great ability of D-glucitol itself to retain solvent. Adducts of alkaline-earth metal salts, however, are more strongly solvated by alcohol than adducts of alkali metal salts. For example,21 lactose CaClj 4 MeOH is relatively stable at 60° at atmospheric pressure under vacuum (< 19 mm. of Hg), a molecule releases only two of the four molecules of methanol. From aqueous alcoholic media, adducts of alkaline-earth metal salts tend to crystallize as hydrates. 

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