Mannide

One of the dianhydrohexitols, B, was identified with l,5 3,6-dianhy-dro-D-mannitol (neomannide, see below), but the other two, A and C, remain of unknown structure. An interesting observation concerning the dianhydride A has been made.48 When l,6-dichloro-l,6-didesoxy-D-mannitol was treated with sodium methoxide a new crystalline dianhydrohexitol was obtained. This had m. p. 118-119° but showed la]D + 33.6°. It was therefore the enantiomorph of dianhydride A. Furthermore, when dichloro-didesoxy-D-mannitol is treated with sodium amalgam yet another dianhydride was isolated. This had m. p. 118-119° and fa]D + 93.6° and is doubtless identical with the /3-mannide of Siwoloboff.49... 

Two other dianhydrohexitols are known. One was prepared over sixty years ago by Siwoloboff66 and was named /3-mannide and the other, neomannide, was prepared by Hockett and Sheffield68 in 1946. The... 

There are two double anhydrides of mannitol, namely, isomannide and /3-mannide the following formulas have been assigned to these compounds. 

Mineral Oil Hydraulic Fluids. Absorption of a mineral oil in an emulsion was apparently very slow in female rats injected subcutaneously with 0.1 mL and in squirrel monkeys injected intramuscularly with 0.3 mL (Bollinger 1970). The emulsion contained 1 volume mannide monoleate, 9 volumes mineral oil, and 9 volumes water [14C]labeled hexadecane, a major component of the mineral oil, was added to the emulsion as a radiotracer. At 1 week and 10 months after treatment, radioactivity remaining at the sites of injection accounted for 85-99% and 25-33%, respectively, of the administered radioactivity. 

The adjuvanticity of oil emulsions was first recognized in the early 1900s. However, the first such product to gain widespread attention was Freund s complete adjuvant (FCA), developed in 1937. This product essentially contained a mixture of paraffin (i.e. mineral) oil with dead mycobacteria, formulated to form a water-in-oil emulsion. Arlacel A (mannide mono-oleate) is usually added as an emulsifier. 

DLSA are rigid diols. They have the same skeleton as isosorbide and LAGA. For instance, 1,4 3,6-dilactone of mannosaccharic acid is a dicarbonyl derivative of iso-mannide and monocarbonyl derivative of the lactone of the anhydromannonic acid. Therefore, DLSA could find applications as diols and their polymers are expected to have similar properties to that of isosorbide and LAGA polymers. 

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 relatively low toxicity of the partial esters of the hexitol anhydrides makes them desirable emulsifiers for injectable medications. D-Mannide mono-oleate was used in a patented, single-injection, vaccine composition122 and in an adjuvant vaccine.123... 

Mannide monoK>leate is a viscid, oily liquid with a yellow color. Its solubilities in various common solvents are similar to those of edible fixed oils and its odor is characteristic, resembling that of vegetable fixed oils. 

Evans, and those associated with him, found that mannide mono-oleate was neither acutely nor chronically toxic in the diet of the white rat or in the diet of the Macacus rhesus monkey. The ester was shown to be absorbed from the intestinal tract of the rat. It was not re-excreted into the gut. Evidench of metabolism was produced by the isolation of crystals of isomannide from the urines of rats ingesting the compound. 

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