Of D-mannitol

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

Finally, the nucleophile to a lithiated epoxide need not be the base originally used to generate it, or even one that has been externally added, but can be another lithiated epoxide. This disproportionation/carbenoid dimerization of (enantio-pure) lithiated epoxides provides 2-ene-l,4-diols (Scheme 5.33) [53]. Syntheses of D-mannitol and D-iditol in three steps from (S) -tritylglycidyl ether were achieved with this method. 

Several of the intracellular teichoic acids are polymers of glycerol phosphate or ribitol phosphate. An unusual teichoic acid, composed of d-mannitol phosphate, and with pyruvic acid linked as an acetal to 0-4 and 0-5, has been isolated from Brevibacterium iodinum. ... 

Another procedure for preparing 4-hydroxy-4,5-dihydroisoxazole 2-oxides derivatives in 86-100% yield, and published by the same group [27], is based on an oxidative cleavage of D-mannitol-derivatives furnishing 2 equiv. of identical enantiopure (2R)-2-methanesulfonyloxyaldehydes which can react with a-nitroacetate in the usual manner. 

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). 

Intramolecular displacement of primary sulfonyloxy or halide groups in derivatives of D-mannitol can also be brought about under basic conditions, albeit in low yield. Treatment of l,6-di-0-(methyl-sulfonyl)-D-mannitol (78), or the corresponding dichloride derivative, with sodium methoxide gave 2,5 3,6-dianhydro-D-glucitol74 (79). Treatment of the latter with hydrochloric acid at 100° in a sealed tube gave the 6-chloro-6-deoxy derivative (80), which was converted into the known 2,5-anhydro-l,6-di-0-benzoyl-D-glucitol45 47 (32). The sequence 78-80 is of interest in the context of C-/3-D-nucleoside precursors, but it suffers from the fact that yields are low. 

Digressing from reductive desulfurization into stereochemistry, we may use this experimental proof of the equivalent symmetry of D-mannitol as a basis for an independent proof of the configurations of D-mannitol and D-arabitol. The reduction of D-arabinose yields the optically active pentitol, D-arabitol application of the Sowden-Fischer synthesis to D-arabinose yields D-mannose86 which upon reduction gives D-mannitol. 

In the formula for D-mannitol (XIV), by Emil Fischer s second convention,84 the hydroxyl on carbon atom 5 is placed on the right. Since D-arabitol (XV) is optically active, the hydroxyl on carbon atom 3 must then be on the left, for regardless of the configuration at carbon atom 4, arabitol would otherwise be an optically inactive meso form. Finally, by reason of the equivalent symmetry of D-mannitol, the... 

Another proof of the configuration of D-mannitol and also of D-manno-n-manno-octitol (XVI), which is likewise dependent on the experimental proof of the equivalent symmetry of D-mannitol is the following. D-Mannose has been converted, by successive cyanohydrin syntheses, first to a mannoheptose and then to a mannooctose which on reduction yielded a mannooctitol whose octaacetyl derivative is optically inactive. (It was not possible to examine the octitol itself because of its very low solubility in water.)87 The meso character of the octaacetate shows that the mannooctitol must possess a meso configuration, with a plane of symmetry between carbon atoms 4 and 5. To write its formula, the hydroxyl at carbon atom 7 is placed on the... 

Montgomery and Wiggins47 have studied the reaction of D-mannitol with hydrochloric acid in detail and the results throw some light on the mode of formation of isomannide from D-mannitol. When D-mannitol is heated under reflux with hydrochloric acid for several days, isomannide results in about 35-40% yield. But when D-mannitol is heated under pressure with fuming hydrochloric acid l,6-dichloro-l,6-didesoxy-D-mannitol (40% yield) and very little isomannide are formed. On examination of the residues after separation of isomannide from the first reaction mentioned above, no fewer than two monoanhydrohexitol derivatives and three new dianhydrohexitol derivatives were encountered. The products isolated are summarized in Table II. 

The simultaneous preparation of both isosorbide and isomannide from sucrose has been achieved.57 This process entailed the hydrogenation of sucrose to a mixture of D-mannitol and D-sorbitol and the subjection of this mixture to dehydration in the presence of acid catalysts followed by fractional distillation.68... 

Closely related to the synthetic work reported in the previous section is the incorporation (131) of a 2,5-anhydro-3,4Hdi-0-methyl-D-mannitol residue (Figure 15) into the 18-crown-6 derivative d-91. Other derivatives of D-mannitol that have been built into crown ether receptors include l,4 3,6-dianhydro-D-maiuiitol (132), l,3 4,6-di-0-methylene-D-marmitol (13 134), and 1,3 4,6-di-O-benzylidene-D-mannitol (134). Examples of chiral crown compounds containing these residues include dd-92, dd-93, d-94, and d-95. Although not derived from carbohydrates—but rather (135) from the terpene, (-t-)-pulegone—... 

In a few cases, two pyridine rings have been incorporated into 18-crown-6 derivatives. Examples are provided by ll-188 (89) and dd-189 (168) that contain, as their sources of chirality, the bis(A, iV-dimethylamide) of L-tartaric acid and the l,2 5,6-di-0-isopropylidene derivative of D-mannitol, respectively. 

Conditions are slightly different during the so-called mannitol fermentation of sugars, especially of D-fructose. The process, which has been known for a long time, has recently been investigated more thoroughly by Bolcato. He found that 3 moles of D-fructose yield 2 moles of carbon dioxide, 2 moles of acetic acid and 2 moles of D-mannitol. Up to now, a maximum of 60% of the theoretically possible amount of D-mannitol has been isolated. The mechanism of the reaction may be assumed to be as follows ... 

The story of the hexitols begins with the discovery of D-mannitol by Proust in 1806. So far as the writers are aware, a review of the hexitols has not appeared previously even though the history of these compounds... 

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. 

The complexes with boric acid and borates have been of more interest. The ability of D-mannitol to render boric acid more acidic is well known and forms the basis of an anal3rtical method allowing boric acid to be titrated as a monobasic acid. The boric acid complexes have been... 

The separation of mixtures of hexitols has long been a difficult problem. The removal of sorbitol from L-iditol by bacterial action is a classical example. Destruction of one component as a means of separation is drastic and is applicable to only a few mixtures. Even from an analytical point of view, separation has been difficult. The proportions of D-mannitol and sorbitol in the reduction products of D-fructose may be determined approximately by crystallizing and weighing the D-mannitol, but the amount of D-mannitol still in solution remains an unknown quantity. 

Oxidation of cyclic sulfites to sulfates was accomplished with RuClj/aq. Na(IO )/CH3CN-CCiyO°C and a large-scale oxidation of D-mannitol-l,2 5,6-diacetonide-2,3-cyclic sulfite to the sulfate described (Fig. 5.17) [437]. The system RuO /aq. Na(10 )/CHCl3 converted cyclic sulfite diesters to the sulfates (Fig. 5.18) [438]. Oxidations of thiophene and aUcyl- and aryl-substituted thiophenes by RuCyaq. Na(ClO) were compared with similar reactions effected by stoich. [MnOJ- [439]. 

A similar simple formation of a cyclopropane ring is the conversion of 3 into 4 in >92 % yield upon treatment of 3 with potassium < rf-butoxide in THF at 0°C for 10 min67. Since 3 is a derivative of D-mannitol the lactone 4 was furnished in optically pure form [a] + 46.8 (r = 1.0, CHC13) mp 66-67°C. 

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. 

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