L-Mannitol

D,L-Mannitol has been obtained by sodium amalgam reduction of D,L-mannose. The identical hexitol is formed from the formaldehyde polymer, acrose, by conversion through its osazone and osone to D,L-fmctose (a-acrose) followed by reduction (83). 

B. 3,4-O-Isopropylidene-L-mannitol (3). A 2-L, single-necked, round-bottomed flask equipped with... 

The reaction was monitored using TLC with 5% MeOH/CH2C2 as the eluent. The desired monoacetonide 3 has a Rf = 0.25. It was desirable to run the reaction to the point where most of the higher Rf components were consumed. This will produce some unwanted L-mannitol that can be filtered off as described above. 

The L-mannitol recovered in this manner could be recycled if desired. 

L-Rhamnitol (L-Rha-ol) or 1-deoxy-L-mannitol 2-Carb-19.2. meso Forms... 

Figure 4.3 Effect of a variety of anti-free-radical interventions on reperfuslon-induced ventricular fibrillation In the Isolated perfused rat heart. Regional Ischaemia was induced by occluding a snare around the left anterior descending coronary artery and, after 10 min, hearts were reperfused by releasing the snare. Superoxide dismutase (SOD) (1 x 10° U/l), catalase (CAT) (1 X 10 U/l), mannitol (Mann) (50 mM), l-methlonlne (Methlon) (10 mM), glutathione (Glutath) (10 iiM) or desferrioxamlne (Deafer) (150 iim) were included throughout the experimental time course (n = 15/group). Redrawn with permission from Bernier et af. (1986).

Very little was published on the synthesis of hexitols from unsaturated intermediates between the time of Griner s work and 1933, when it occurred to me that it might be possible to add four hydroxyl groups to divinylglycol by means of a solution of silver chlorate containing a small amount of osmic acid. In carrying out this work I had the assistance of one of my students, Joseph Wiemann. We succeeded far beyond our expectations and obtained allitol, unknown up to that time, and d,l-mannitol. 

An amount of 16 g. of the glycol (m. p. 18°) dissolved in 250 ml. of water was oxidized with 18 g. of silver chlorate and 0.3 g. of osmic acid. The reaction mixture yielded 3 g. of allitol and no D,L-mannitol. We may therefore assign the meso configuration to the divinylglycol melting at 18°, since on hydroxylation it yielded allitol, but not D,L-mannitol. 

The mother liquor was then treated with a small amount of ether, whereupon it separated into two layers. The lower layer consisted of a black sirup, which, when treated with absolute alcohol very slowly deposited some crystals, 1 g., consisting largely of D,L-mannitol. The upper layer was treated with a large volume of ether, which caused the precipitation of a considerable quantity of a brown sirup. Crystallization began almost immediately, especially when the sirup was treated with absolute alcohol. The crystals were collected and there was obtained in this way 12 g. of crude allitol. After solution in water and precipitation with alcohol, the crystals melted at 140°, but still contained a small amount of impurity. After several recrystallizations they melted at 149°. 

Upon standing, the mother liquor deposited more allitol—some 3 g. after a period of two months. No crystalline material was obtained from the ethereal solution. We thus obtained from 100 g. of divinylglycol, 11 g. of D,L-mannitol and 15 g. of allitol. 

Optically pure glyceraldehyde acetonides are widely used in the synthesis of enantiomerically pure compounds (EPC synthesis).1 2 3 4 5 Whereas D-(R)-glyceraldehyde acetonide is easily obtained from the inexpensive D-mannitol,6 7 there are only a limited number of practical syntheses of the enantiomeric L-(S)-glyceraldehyde acetonide.8 9 Difficulties arise from different sources 1) availability of the starting material diisopropylidene-L-mannitol 2) length of the synthesis 10 3) nature of the reactants used mercury acetate, mercaptans, lead tetraacetate, ozone at -78°C, 4) moderate yields.11 14... 

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... 

A. E. Hakansson, J. van Ameijde, L. Guglielmini, G. Home, R. J. Nash, E. L. Evinson, A. Kato, and G. W. J. Fleet, Looking glass inhibitors Synthesis of a potent naringinase inhibitor l-DIM (l,4-dideoxy-l,4-imino-L-mannitol), the enantiomer of DIM (l,4-dideoxy-l,4-imino-D-mannitol) a potent a-D-mannosidase inhibitor, Tetrahedron Asymmetry, 18 (2007) 282-289. 

L-Mannitol has been prepared by the reduction of L-mannosaccharo-dilactone or L-mannose. By far the most convenient procedure is that used by Baer and Fischer for their preparation of L-glyceraldehyde by the oxidative cleavage of l,2 5,6-diisopropylidene-L-mannitol with lead tetraacetate. L-Arabinose was converted to L-mannonolactone by the cyanohydrin synthesis and this was hydrogenated over platinum oxide to the desired L-mannitol. High hydrogen pressures, rather than low as usually employed with this catalyst, were used. 

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. 

It should be noted that the following positions are synonymous in D- or L-mannitol and d- or L-iditol 1 and 6, 2 and 5, and 3 and 4. Sorbitol, because of lower optical symmetry, would form even more derivatives. The number of possible acetals is much smaller and that of metallic complexes still smaller. The number of various theoretical permutations of mixed ether-esters, ether-acetals, etc., utilizing readily available reagents, runs into the hundreds of thousands. 

L-Mannitol does not occur naturally but is obtained by the reduction of L-mannose or L-mannonic acid lactone (80). It can be synthesized from the relatively abundant L-arabinose through the L-mannose and L-glucose cyanohydrins, conversion to the phenylhydrazines which are separated, liberation of L-mannose, and reduction with sodium borohydride (81). Another synthesis is from L-inositol (obtained from its monomethyl ether, quebrachitol) through the diacetonate, periodate oxidation to the blocked dialdehyde, reduction, and removal of the acetone blocking groups (82). 

On deamination, 2-amino-l,5-anhydro-2-deoxy-l>mannitol gave l,5-anhydro-2-deoxy-D-eryf/iro-3-hexulose as the major product.54 The substitution product 1,5-anhydro-D-glucitol was formed to a small extent, and inversion again predominated, as with other axial amines (60, 72, and methyl 4-amino-4-deoxy-a-D-galactopyranoside) this is in accord with the predominant inversion of configuration reported for deamination, in water-rich media, of simple cyclohexyla-mines,154 and aminodecahydronaphthalenes39 in which the amino group is axial. As discussed previously (see p. 15), the extent of inversion can vary considerably with the nature of the solvent, and steric factors appear to be important in deaminations of per-O-acetyl amines (see pp. 37 and 49). 

C7HMOe NaCl 2,5-O-Methylene-L-mannitol-sodium chloride19... 

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