Inositols periodate oxidation

Base-catalyzed nitromethane cyclizadonof the thaldehyde generated by periodate oxidation of 1,3-O-cyclohexyhdene-myo-inositol affords the nitrodiol with l,4/3,3,5-coti iguration This is converted into the ct-marmosidase inhibitor, marmostadn A fEq 3 60 ... 

A. Inositol Phosphates.—Phosphatidyl inositol (71) is hydrolysed in mammalian tissues to wyo-inositol 1,2-cyclic phosphate (72).i myoinositol 1-phosphate (73) is released simultaneously but is not converted into (72) by the enzyme system. Periodate oxidation of (73) liberates orthophosphate quantitatively, the unstable dialdehyde phosphate (74) being an intermediate. Little or no orthophosphate is released from glucose 6-phosphate under the same oxidative conditions, and this reaction has been used to assay (73). 

Base-catalyzed nitromethane cyclization of the dialdehyde generated by periodate oxidation of 1,2-O-cyclohexylidene-myo-inositol affords the nitrodiol with 1,4/2,3,5-configuration. This is converted into the a-mannosidase inhibitor, mannostatin A (Eq. 3.60).98... 

Reaction (a) takes place first, but two reactions, (b) and (c), can then occur simultaneously, to give different products. Reaction (b) seems to predominate, although (c) does take place. A stepwise reaction has also been observed in the periodate oxidation of mi/o-inositol.41 60 62... 

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). 

Some choice between the two possible mechanisms can be made by studying the periodate oxidation of pinitol,66 sequoyitol,78 and profo-quercitol.79 If a methylene (deoxy) or an O-methyl group should occur at C3 or C4 of the hexodialdose, the rapid periodate oxidation of the cyclic form XXXVI would end after the consumption of only 2 or 3 moles of periodate per mole, respectively, and would then continue only at the very slow rate governed by the hydrolysis of the formate ester. The above compounds give hexo-dialdoses of this nature, but they rapidly consume some four moles of periodate per mole. This indicates that the major path of the reaction is not the one by way of cyclic intermediates this conclusion is probably valid for the inositols, too. 

These treatments convert to ionic substances, and remove, nearly all constituents of natural materials the acid treatments release any inositol present as phosphate, or combined in phospholipids, glycosides, etc. Glycerol remains in the deionized sample, but it can be oxidized separately, or be removed by heat decomposition or by repeatedly evaporating the solution to dryness. Such polyhydric alcohols of greater chain length as erythritol and mannitol, when present, would still interfere. However, corrections can be made for these compounds by determining the formaldehyde which they form on periodate oxidation, or they may be removed by chromatography on filter paper. The micro-periodate method is well suited to the analysis of samples eluted from filter paper, provided that care is exercised to remove the tiny particles of cellulose which are usually found in such eluates. 

Although pinitol and quebrachitol are resistant to the action of Acetobacter svboxydans, Chargaff and Magasanik have reported that Zewo-inositol is oxidized by this organism to a tetrahydroxycyclohexane-dione. Since the phenylosazone from this compound consumes three moles of periodic acid, the authors concluded that the carbonyl groups were adjacent. A similar compound was obtained from deiZro-inositol although in smaller yield. 

Synthesis from myo-inositol Total syntheses of trehazolin (1) and its isomers have established both its structure and absolute configuration (Schemes 11-13). Thus, base-catalyzed nitromethane condensation of the dialdehyde generated by periodate oxidation of ( )-l,2-(9-cyclohexylidene-myo-inositol (74) gave a mixture of the nitro-diols, which was hydrogenated in the presence of Raney nickel, followed by acetylation to afford the three diastereoisomeric 2,3-(9-cyclohexylidene derivatives 75 (40%), ( )-76 (5%) and 77 (5%) of 5-acetamido-l,4-0-acetylcyclopentane-l,2,3,4-tetraol. The minor racemic mixture 76 was de-O-acetylated, N,0-isopropylidenated, and then resolved by... 

GIPC-derived oligosaccharides from S. schenckii were liberated by ammonolysis and analyzed by methylation analysis and NMR. The position on the inositol to which the phosphorylceramide group is attached was deduced by a combination of methylation and periodate oxidation studies. The ceramide moiety was linked to position 1 via a phosphodiester bridge. The oligosaccharide structures are shown in Table 2. 

A similar route has been suggested to account for the formation of glyoxylic acid (18, R = H) and methyl glyoxylate (18, R = Me) during the periodate oxidation of inositols and (9-methylinositols, respectively. Formation of these carboxy derivatives was depicted by sequences involving enolization to such reductones as 16, which are hydroxylated to 17 and then cleaved oxidatively. 

As formic esters are not products of these periodate oxidations, a hexodi-aldose, such as 29, must react in an acyclic form however, inositol shows exceptional behavior, in that it affords a high yield of a formic ester, which must be derived by cleavage of a furanose form of the intermediate hexodialdose. Cyclization of the latter is regarded as being favored by the all-trans arrangement of groups on its furanose ring. ... 

The first step in the oxidation of a cyclitol is the formation of a hexo-dialdose (XXXV) this can either react with more periodate in its straight-chain form or rearrange first to a cyclic form. The latter change clearly occurs in the oxidation of dambonitol69 (1,3-di-0-methyl-m /o-inositol, XXXI), in which only about 0.2 mole of the formic acid produced is found in... 

Periodic Acid Oxidation. Treatment of the above derivative with periodic acid (in slight excess of theory for one v/c-glycol) at room temperature showed a quantitative conversion of the sample to glycoaldehydephospho-inositol and formaldehyde (Brockerholf and Hanahan, 1959). The results showed that the attack was only on the glycerol portion of the molecule because the attack of inositol, which must be done at an elevated temperature, would not yield formaldehyde. Thus, it was concluded that the glycerol was attached to the inositol molecule via a phosphate ester group. 

The oxidation of meso-inositol by periodic acid, studied by Fleury and... 

Six moles of periodic acid were consumed per mole of streptamine with no formation of formaldehyde. - - Under comparable conditions, meso-inositol (m. p. 225°) was stated to consume six moles of periodic acid (formic acid was not detected or measured) and to give no formaldehyde while D-mannitol under like conditions consumed five moles of oxidant with the formation of two moles of formaldehyde. It is noteworthy that the periodic acid oxidation of the unsubstituted natural meso-inositol (see page 46) had been shown by Fleury, Poirot and Fievet to be anomalous (see page 51). 

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