Cyclitols oxidation

Further progress on the problem of the stereochemical specificity of cyclitol oxidation by A. suboxydans will depend on the isolation of the enzyme or enzymes involved. Cell-free preparations capable of oxidizing wn/o-inositol have been obtained,43 44 but these have not been further purified. The enzyme is apparently a true dehydrogenase, since it can couple with diaphorase.44... 

The power of the new spectrometer to reveal configurations of difficult cyclitols or sugars was first tested with mt/o-inositol (2), using deuterium oxide as solvent. At 60 or 100 MHz. the one equatorial and five axial protons appear to have different chemical shifts as shown by Lemieux in 1956 with a 40 MHz. instrument (14,15). However, since the five-proton axial signal could not be resolved, one could probably not have assigned the configuration 2 (which was already known from laborious chemical correlations extending over many years.)... 

Remarkable selectivity has been observed in the oxidation of molecules containing several secondary hydroxyl groups, such as al-dopentopyranosides, 6-deoxyaldohexopyranosides, cyclitols, and various anhydro derivatives. As indicated previously, attack usually occurs at relatively hindered hydroxyl groups. When aqueous solutions of benzyl /3-D-arabinopyranoside, benzyl jS-D-ribopyranoside,... 

The condensation step is catalyzed by the glycosyltransferase SpcF. Further enzyme-catalyzed oxidation is probably needed for the introduction of the hemiketal linkage between cyclitol and sugar units. The SpcY enzyme, which has a similar counterpart, HygY, among the /lyg-cluster encoded proteins (see Section 2.2.4.3.1), is a candidate enzyme for this reaction. SpcY is a member of the radical SAM superfamily of proteins and relatives of SpcY have been found before all in connection with molybdenum-cofactor biosynthesis but to our knowledge no details of the mechanism involved is known for those. 

The known adduct (385) of furan and vinylene carbonate, previously used for the synthesis of some cyclitols,256,257 has been transformed into DL-ribose derivatives. After hydroxylation of 385 and subsequent formation of the isopropylidene derivative, the carbonate group was removed by treatment with barium hydroxide, and the resulting diol was cleaved by oxidation with permanganate. Dicarboxyl-ic acid 386 gave, upon treatment with acetic anhydride, cyclic anhydride 387. The reaction of 387 with azidotrimethylsilane produced... 

The stereospecificity of the oxidation of cyclitols and deoxycyclitols by Acetobacter suboxydans has been defined by Magasanik, Franzl and... 

The regioselectivity of the migration in Baeyer-Villiger oxidation of ketones is very dependent upon substituents attached to carbon atoms adjacent to the ketone. In a study128 of the MCPBA oxidation of polyhydroxycyclohexanone derivatives, the regioselectivity of the reaction has been carefully identified. This should prove useful to synthetic chemists when planning to use this type of reaction, since cyclitols are important synthons in natural product synthesis. 

It is clear that the two strains of A. suboxydans differ in the degree of selectivity with which they oxidize axial hydroxyl groups in cyclitols. However, both strains can be used in growing cultures to prepare (from cyclitols) mono- and di-ketones by the selective oxidation of one, or two, hydroxyl groups. As suggested by Anderson and coworkers,42 the rules are a useful guide for predicting which positions will be oxidized. 

Cyclitol dehydrogenases have also been detected in some strains of Aero-bacter aerogenes46 and in Mycobacterium tuberculosis BCG.46 The Aerobacter enzyme has been fairly extensively studied,45 47 and it is considered to function in the fermentation of inositol by this organism.38 Pseudomonas beijerinckii is distinguished by its ability to oxidize m /o-inositol and levo-inositol to the tetrahydroxyquinone stage,48 and Propionibacterium pento-saceum effects a dismutation of rayo-inositol in which hexahydroxybenzene appears to be the oxidized product.49... 

With pinitol and quebrachitol, the reaction is highly selective for one of the two axial hydroxyl groups in each compound (see formulas LXIII —> LXVII, and LXV —> LXIX, p. 170).61 This selectivity shows the steric effect of the methyl group. Nevertheless, the platinum-catalyzed dehydrogenation (in contrast to the action of Acetobacter) is not easily inhibited by substitution in the cyclitol molecule even the hindered axial hydroxyl groups in dambonitol (LXXVII) and in O-isopropylidenequebrachitol (LXVI, see p. 172) can be oxidized.62 63... 

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... 

A colorimetric method for determining mz/o-inositol has been described.104 The color is developed with the phosphomolybdotungstic acid reagent of Folin and Denis, after oxidation of the inositol with bromine. Enzymic methods, based on the inositol dehydrogenases of Acetobacter suboxydans44 and Aerobacter aerogenes,106 have also been used. These methods could be employed with any cyclitol readily attacked by the respective enzyme systems (see pp. 144 and 147). 

Only one diketone (2,5-diketo-ma/o-inositol) of the cyclitol series has been isolated in the crystalline state. However, there is ample evidence that a number of other cyclitol diketones have been obtained. Thus, solutions of dearfro-inositol and Zewo-inositol which have been oxidized by Acetobacter... 

Aldol-type cyclization of dialdehydes with nitroalkanes is a valuable synthetic route to amino sugars, amino cyclitols and nucleosides of amino sugars. Recently, the cyclization of the di- and tetra-alde-hydes d ved from sucrose (15) with nitroalkanes has appeared. It is noteworthy that the oxidative cleavage of sucrose with LTA affords the dialdehyde selectively (Scheme 8). ... 

The reaction of cyclohexene with AT-(phenylseleno)phthalimide in the presence of (S,S)-hydrobenzoin in methylene chloride afforded two diastereomeric oxyselenides (38 and the (li , 2R) diastereomer) in a 1 1 ratio. Compound 38 was separated and converted into the olefin 39 via selenoxide elimination. The second PhSeOTf promoted oxyselenenylation reaction gave only the cis fused bicyclic dioxane 40. Oxidation and subsequent elimination provided the olefin 41. This is the key intermediate for the syntheses of the cyclitols 42 and 43, that were obtained from a series of classical reactions as indicated in the Scheme. Oxyselenenylation reactions have also been employed to promote glycosylation reactions [43]. 

Akiyama, T, Okada, K, Ozaki, S, The preparation of optically active A -isoxazolines via addition of nitrile oxides to chiral acryloyl esters bearing cyclitols as auxiliaries. Tetrahedron Lett, 33, 5763-5766, 1992. 

A rearrangement may be involved in the oxidation of the inositol derivative (4) to the hemiacetal lactone (5),36 a key step in the conversion of cyclitols to hexoses. 

---