Hexitols preparation

A different monoanhydro-di-O-benzoyl-D-hexitol prepared from D-mannitol, designated 2,5-anhydro-l,6-di-0-benzoyl-D-mannitol (XXXIV, R = benzoyl),100 was reported to consume no lead tetraacetate, presumably... 

Evaluation of nine l,4-dideoxy-l,4-imino-hexitols, prepared by strategies I and II, are reported elsewhere (2,12). Among other results, some interesting (22) and selective (72) a-D-mannosidases were found. 

Besides these normal technical products, many other different types of a-sulfo fatty acid esters have been described in the literature. For example, Weil et al. prepared a-sulfopalmitates and stearates with higher alcohols [19] and also monoesters of polyhydric alcohol [39] and of hexitols and sucrose [40] for their special properties. In addition to the sodium salt, Stirton et al. used other cations, such as Li, NH4, K, Mg, and Ca, to study the relationship between the structure and the surfactant properties [30]. 

II. Synthesis of Hexitols from Unsaturated Intermediates 1. Methods of Preparation... 

Crystalline 1,4-anhydro-D-sorbitol is of much more recent origin than 1,4-anhydro-D-mannitol, inasmuch as its preparation was first recorded in 1946.10 It was obtained by the restricted dehydration of D-sorbitol and has been given the trivial name arlitan. Two groups of workers simultaneously effected proof of its constitution. Hockett and coworkers11 treated the anhydride with lead tetraacetate and since its rate of oxidation coincided with that of ethyl D-galactofuranoside and since one molecular proportion of formaldehyde was formed, the authors concluded that the ring must involve Cl and C4 of a hexitol chain. Assuming that no other carbon atoms are involved, sorbitan is either 1,4-anhydro-D-sorbitol or 1,4-anhydro-D-dulcitol (Walden inversion at C4 of the sorbitol molecule). They therefore synthesized 3,6-anhydro-D-dulcitol (enantio-morphous with 1,4-anhydro-L-dulcitol) but found it to be different from arlitan. 

The hexitol anhydrides also have medicinal uses.97 Carr and Krantz98 found that l,4 3,6-dianhydro-D-mannitol was quite non-toxic to man and was a valuable diuretic. The dinitrates of both isomannide and isosorbide" have possible uses as agents for lowering blood pressure, though Burn and Stephenson100 found that the D-sorbitol derivative was twice as active as the D-mannitol derivative in this respect. 2,5-Diam-ino-2,5-didesoxy-l,4 3,6-dianhydro-D-mannitol and -D-sorbitol have been prepared and their sulfanilamido derivatives obtained.101 These however showed no outstanding bacteriostatic activity. 

One would also think that saccharides are more attractive starting raw materials for direct preparation of epoxy resins than hydrocarbons since they already possess oxygen atoms needed for the epoxy rings. Such diepoxy derivatives of hexitols are known compounds, for instance 1,2 5,6-dianhydro-3,4-0-isopropylidene-D-mannitol (XIX). Their preparation, however is difficult and requires 15 to 18 steps which proceed in very low overall yield (17-19). 

As a first step in this direction, we have been able to prepare 1,2 5,6-dianhydro-3,4-0-isopropylidene-D-mannitol as a model diepoxy hexitol derivative in four steps with overall 50% yield according to the following scheme ... 

L-Iditol (sorbi6rite), the last of the four naturally occurring hexitols, occurs in service berries along with sorbitol. After removing sorbitol from the juice by fermentation to L-sorbose with the sorbose bacterium, Acetobacter xylinum, the n-iditol is crystallized as a benzylidene derivative. It has been prepared by the action of sodium amalgam on... 

It is evident that syntheses of the Lespieau type can lead to a great number of polyhydroxy compounds. Wiemann has prepared compounds such as CHsCH2(CHOH)6CH2CH3, which he calls diethyl mannitol. It would seem better to designate this substance a tetra-desoxy decitol or decane hexol since its configuration is not known with certainty. Apparently this type of synthesis leads to symmetrical arrangements of hydroxyl groups, since allitol, dulcitol and D,L-mannitol are the only hexitols that were identified as products. 

The organic esters have a greater order of stability, but it is difficult to prepare completely acylated compounds without concurrently anhy-drizing the hexitol unless one uses acid anhydrides or chlorides. Early attempts to prepare higher aliphatic esters of D-mannitol resulted in the formation of mixtures of mannitans and mannides. It is for this reason that caution must be exercised in interpreting some of the work in the literature. The analytical values of the pure compounds and the mixtures are such that one cannot differentiate between them. 

To summarize, crystalline l,4-dideoxy-l,4-imino-hexitols are readily prepared from 2,6-dibromo-2,6-dideoxy-hexonolactones in gram quantities without any use of chromatographic separations. The bromolactones may, prior to treatment with aqueous ammonia, either be converted into the 2,3-epoxides by treatment with KF or K2CO3 in acetone, or may be reduced with sodium borohydride in water to give the bromodeoxyhexitols. 

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. 

LespiEau, R., Synthesis of Hexitols and Pentitols from Unsaturated Poly-hydric Alcohols, 2, 107-118 Levi, Irving, and Purves, Clifford B., The Structure and Configuration of Sucrose (ofplia-D-Glucopyranosyl beta-n-Fructofuranoside), 4, 1-35 Levvy, G. A., and Marsh, C. A., Preparation and Properties of 0-Glucuronidase, 14, 381-428 Levvy, G. A. See also, Conchie, J. Liggett, R. W., and Deitz, Victor R., Color and Turbidity of Sugar Products, 9, 247-284... 

The low boiling component was isolated by fractional distillation at 80°-85°C (13 mm pressure). The material was impure -2 acetoxy-methyltetrahydropyran (I). The isolation and characterization of the two other components are described in relation to the preparation of 7 and l,5-anhydro-2-deoxy-D-it/xo-hexitol. 

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