Meso-Inositol

For all the substrates discussed so far the peptide catalysts employed had to differentiate between enantiomeric substrate molecules. Miller et al. subsequently screened peptide libraries for members able to selectively functionalize enantio-topic hydroxyl groups of meso inositols. In particular, they were able to convert myo-inositol 35 to either monophosphorylated D-myo-inositol-l-phosphate 37 or d-myo-inositol-3-phosphate ent-37 in high yield and excellent ee (98% Scheme 12.18) [38, 39], This remarkable result was achieved by use of either of the penta-... 

Nicotinic acid Phosphorus oxychloride meso-Inositol... 

The myo-isomer is the most abundant form in nature. It occupies a unique place in inositol metabolism because this is the only isomer synthesized de novo from D-glucose-6-phosphate all other isomers are derived from myo-inositol (Loewus, 1990b Loewus and Murthy, 2000). In early 1900s, myo-inositol was called meso-inositol (abbreviated ms-inositol) probably because, like mesotar-taric acid, it does not exhibit optical activity and cannot be resolved into optical isomers (Posternak, 1965). However, as discussed above, six other isomers also do not exhibit optical activity so the name seemed inappropriate. In 1954, the name myo-inositol was introduced - a name not particularly well coined either since it is a pleonasm - both myo and inositol mean muscle. Nevertheless, the name persists. 

SYNS cis-l,2,3,5-trans-4,6-CYCLOHEXANEHEXOL i-INOSITOL meso-INOSITOL... 

The very widespread occurrence of meso-inositol (m. p. 225°) in both plant and animal sources makes this substance by far the most extensively investigated of the cylitols in fact, the comparative rarity of the other inositols has justified the general retention of the name inositol to denote meso-inositol although, as pointed out above, the term has been extended to its isomers, meso-inositol and the equally common name, inactive inositol, are obviously poor names for this compound since six of the other inositols are also optically inactive. The sole attempt at a rigorous systematic nomenclature for the cyclitols is that of Maquenne who suggested the use of a fraction to denote the positions of the hydroxyl... 

From these facts Maquenne concluded that he was dealing with a hexahydroxycyclohexane. Confirmation of this structure was obtained in 1914 by Wieland and Wishart who found that catalytic reduction of hexahydroxybenzene gave more than a 50% yield of meso-inositol. 

The difficult proof of the configuration of meso-inositol has come only recently from two independent sources, each proof representing the culmination of a long series of researches. The work of T. Posternak, although second in actual priority, will be described first. 

Of the nine possible configurations, VIII and IX were eliminated at the outset since they contain no plane of symmetry and represent optically active compounds while meso-inositol is inactive and unresolvable. The action of phosphatase on meso-inositol hexaphosphoric acid ester ... 

Recourse was then had to the direct oxidation of meso-inositol with alkaline potassium permanganate, and a hexaric acid was obtained which proved to be identical with allomucic acid prepared previously by Emil Fischer. Since the configuration assigned to this acid placed the four hydroxyl groups in a cis-cis-cis relationship, all the remaining configurations for meso-inositol save II are seen to be inapplicable. From the mother liquors of the oxidation mixture D,L-glucosaccharic acid was also isolated. This result, however, only showed that form IV was untenable. 

In 1941 Posternak studied scyllo-meso-inosose (see p. 65), a penta-hydroxycyclohexanone which had been obtained by Kluyver and Bo-ezaardt from the biochemical oxidation of meso-inositol. Cautious oxidation of scyllo-meso-inoaose with permanganate led Posternak to the isolation of a hexaric acid which he identified as n,L-glucosaccharic acid. Since, of the two forms II and V, only II can give an optically inactive inosose oxidizable to D,L-glucosaccharic acid, this evidence appeared to settle the configuration of meso-inositol. 

In 1942, however, Mrs. Gerda Dangschat announced the isolation of D,L-idosaccharic acid from the oxidation of a derivative of meso-inositol. Several months later Posternak published proof that his hexaric acid from the oxidation of inosose was actually n,L-idosaccharic acid and not n,L-glucosaccharic acid. Thus, by two separate paths meso-... 

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

In explanation of this array of facts Fleury, Poirot and Fievet have offered the following mechanism. It is suggested that the meso-inositol molecule is initially attacked at two points with the formation of two moles of tartronic dialdehyde. This dialdehyde then rapidly rearranges HOH... 

This unexpected behavior of meso-inositol with periodic acid serves to emphasize further the dissimilarity of this compound to its acyclic... 

Griffin and Nelson repeated, in part, the work of Muller and made the further observation that acetyl chloride and acetyl bromide react with meso-inositol much as did Muller s glacial acetic acid solution of the hydrogen halides. It may be noted that apparently the same dibromo-didesoxyinositol, melting at 216°, was obtained from meso-inositol and scyllitol (as the tetraacetate by Muller) and from pinitol (monomethyl-dexfro-inositol). 

Majima and Simanuki found that meso-inositol reacts with thionyl chloride only in the presence of pyridine. Among the products isolated was a monochloro-desoxy-inositol, a tetrachloro-tetradesoxy-inositol, a tri- and a tetrachlorobenzene and a tri- and a tetrachlorophenol. 

Apparently complete replacement of the hydroxyl groups in meso-inositol by halogen has never been accomplished. The reverse procedure, hydrolysis of the benzene hexahalides, has likewise failed although Milhorat and Barthels have claimed the synthesis of an a-tocopheryl ether of a cyclitol by heating a-tocopherol with benzene hexachloride in absolute alcoholic potassium hydroxide under an atmosphere of nitrogen. 

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