Aldoses 2-0-methyl

The preparation of crystalline methyl ethers of iV-phenyl- or Af-p-tolyl-aldosylamine by condensation of aniline or p-toluidine with aldose methyl ethers proceeds, in many cases, readily and quantitatively in methanolic or ethanolic solution, either at room or reflux temperature. For this reason, such derivatives are frequently used to characterize aldose methyl ethers isolated during constitutional studies on polysaccharides. For D-glucose, for example, crystalline 2-0-methyl-, 6-0-methyl-,3,4-di-O-methyl-, 2,3,4-tri-O-methyl-, 2,4,6-tri-O-methyl-, " and 2,3,4,6-tetra-O-methyl-A-phenyl-n-glucosylamine have been prepared in this way. Although anomeric forms of A -arylaldosylamine methyl ethers are possible, such anomeric pairs have not been isolated. No similar derivatives have been obtained from ketose methyl ethers. 

Dialdoses [bis(dithioacetals)] D- threo- Tetrodi-aldose methyl 116.0... 

RSH, cond. HCl, 20°, 30 min. These conditions were used to protect an aldose as the methyl or ethyl thioketal. 

Development of (Z, )-5-(2-methyl-3-phenyl-2-propenylidene)4-oxo-2-thio-xothiazolidine-3-acetic acid (Epalrestat, Kinedak), an aldose reductase inhibitor 97YGK651. 

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

Stacey started research in an inspiring and stimulating atmosphere that he strove to maintain, add to, and develop when it became his turn to lead the department. His earliest research was with Haworth and his key partner E. L. Hirst [Adv. Carbohydr. Chem. Biochem., 35 (1978) 1 -29] on aspects of the chemistry of glucoheptose. His first publication with them in 1931 was entitled Walden Inversion in the a-Glucoheptose Series, followed in the next year by a report on the methylation of monocarboxylic acids derived from aldoses and the structure of pentamethyl a-gluco-heptonolactone. He found this to be a difficult project because, initially, he could not crystallize his stock of glucoheptose. Then, as later, he found crystallization to be a challenging problem. 

Methylation of Monocarboxylic Acids Derived from Aldoses. Structure of Pentamethyl a-Gluco-heptono-y-lactone, W. N. Haworth, E. L. Hirst, and M. Stacey, J. Chem. Soc., (1932) 2481-2485. 

Wolfrom, Sowden, and Lassettre measured the rate of hydrolysis of methylated cellulose in fuming hydrochloric acid at 0°C by continuous mere apt alation of the aldose group formed for each bond ruptured. 

Auf 3-O-Methyl- oder 3-O-Glykosyl-hexosen ist dieses Schema direkt anwendbar, und zwar ist es gleichgiiltig, ob die Hexose eine Aldose VI oder eine Ketose VII ist. Denn beide bilden das gleiche Anion VIII. Abspaltung der Glykose bzw. von Methylalkohol und Umlagerung (analog II- V) liefert Metasaccharinsaure IX. 

Coxon and co-workers90 have studied the reaction of naked glyco-OZTs with methyl iodide in the presence of sodium methoxide in methanol and the corresponding 2-methylsulfanyl-glyco-oxazolines were obtained in good yields in many aldose series (Scheme 53). 

From their kinetic results Bishop and collaborators >8) calculated the velocity constants of the furanoside anomerisations of their seven aldoses (Table 1), and rationalised them in terms of ring conformations and group interactions. Thus, for example, in the extreme cases methyl a-D-arabinofuranoside (4), having the fewest non-bonded steric interactions, is the most stable pentofuranoside, while methyl p-o-lyxofurano-side (5), having the least stable ring, reacts most rapidly. 

In another reaction which leads to glycosides, direct and specific C-1 methylation of aldoses may be achieved by the use of diazomethane in aqueous methanol and mixed glycosides result... 

Basnet, P. et al., Five new C-methyl flavonoids, the potent aldose inhibitors from Matteucia orientalis, Chem. Pharm. Bull, 43, 1558, 1995. 

The formation of acyclic enediols is, apparently, the initial reaction that leads to dehydration products. Sugar enediols are transitory compounds that have never been isolated. However, because, when treated with either acid or base, an aldose gives rise to its 2-epimer, as well as to its 2-keto isomer, a persuasive argument is provided for the 1,2-enediol as the intermediate common to each of the products. The evidence in favor of these intermediates is based primarily on isotope-exchange experiments, on reactions that involve isomeriza-tions of O-methyl sugars, and on kinetic measurements.10... 

Using the corresponding (6R) isomer (from D-valine and DL-alanine), alkylation with 2-chloro-3-methyl quinoxaline followed by further transformation has yielded an aldose reductase inhibitor in optically pure form (90T7745). 

Study of this reaction has not been limited to cyclic acetals of aldoses and aldosides, and synthetic applications in the ketose series have been developed,273,276,278,278 particularly for isopropylidene acetals of D-fructose. As an illustration of these reactions, two examples are given here. The action of butyllithium on 2,3 4,5-di-0-isopropyli-dene-l-0-methyl-/3-D-fructopyranose (280) gave273 a 30% yield of the 5-enopyranose 282. Abstraction by the base of the axial hydrogen atom from the 6-methylene group, giving the anion 281, was invoked... 

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