Carbohydrate-derived Alcohols

Schmidt, Methods Carbohydr. Chem. 2 (1968) 318. l,2 5,6-Di-0-cyclohexylidene-a-D-glucofuranose 

Utamura, K. Kuromatsu, K. Suwa, K. Koizanni, T. Shingu, Chem. Pharm. Bull. 34 (1986) 2341. 

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The asymmetric reduction of ketones with modified lithium aluminum hydride is well known. Several reviews of the literature are available2-4-7, as is a comparison of the relative effectiveness of a variety of reagents8. Many of the early studies used terpenoid or carbohydrate-derived alcohols as modifiers, however, ketone reduction rarely proceeded with greater than 20% ee. One problem with these reagents is that the alkoxy aluminum reagent may undergo exchange so that lithium aluminum hydride could be present in solution. 

Carbohydrate-derived alcohols (isomannide and isosorbide) have been examined. In one example, the isomannide derivative 89 was able to react with ketone 90 to afford 91 in excellent yield. 

Carbohydrate derivatives. Alcohol-free ether satd. with water added to a soln. of l-bromo-3,4,6-tribenzoyl-N-benzoyl-a-D-glucosamine in chloroform, and the product allowed to crystallize 1,3,4,6-tetrabenzoyl-a-D-glucosamine hydro-bromide. Y 73%. F. Micheel and H. Kochling, B. 92, 2832 (1959) s. a. H. Weid-mann and H. K. Zimmerman, Jr., B. 92, 2828 (1959). 

FIGURE 6. Carbohydrate derived chiral auxiliaries for the cyclopropanation of aUylic alcohols... 

As a result of these considerations, Tipson29 was able to devise a simple, fairly general method for sulfonylation of monohydric alcohols (and phenols) in pyridine which has since been widely and successfully used it is applicable to sulfonylation of many carbohydrate derivatives. Of the various precautions advocated in the literature as being advisable (including stirring, portionwise addition of sulfonyl chloride, and extensive prepurification of the latter), only two were found to be really necessary in all cases. First, since sulfonyl chlorides are rapidly hydrolyzed by slightly moist pyridine, it is essential that both the pyridine and the... 

When the alcohol possesses no functionality which is susceptible to basic conditions, it may be readily converted into the corresponding methyl ether by treatment with a suitable methylating agent (e.g. methyl iodide or dimethyl sulphate). Typical conditions are described in Expt 5.73, which also include PTC procedures for those alcohols which are water insoluble. Polyols, as for example in the case of carbohydrate derivatives, may also be methylated by this PTC procedure. If the compound to be methylated is base-labile, methylation may be effected by treatment of a mixture of the compound and neutral silica gel in ether solution with diazomethane.75... 

There are many silylating reagents for the conversion of an alcohol into the corresponding silyl ether. The reader should consult the Handbook of the Pierce Chemical Co. for an authoritative survey. The procedure for the formation of trimethylsilyl ethers of carbohydrate derivatives with hexamethyldisilazane/ chlorotrimethylsilyl chloride in pyridine and the subsequent examination by g.l.c. analysis is described in Section 2.31. 

In basic chemicals, nitrile hydratase and nitrilases have been most successful. Acrylamide from acrylonitrile is now a 30 000 tpy process. In a product tree starting from the addition of HCN to butadiene, nicotinamide (from 3-cyanopyridine, for animal feed), 5-cyanovaleramide (from adiponitrile, for herbicide precursor), and 4-cyanopentanoic acid (from 2-methylglutaronitrile, for l,5-dimethyl-2-piperidone solvent) have been developed. Both the enantioselective addition of HCN to aldehydes with oxynitrilase and the dihydroxylation of substituted benzenes with toluene (or naphthalene) dioxygenase, which are far superior to chemical routes, open up pathways to amino and hydroxy acids, amino alcohols, and diamines in the first case and alkaloids, prostaglandins, and carbohydrate derivatives in the second case. 

M. Kunz, H. Puke, C. Recker, L. Scheiwe, and J. Kowalczyk, Process and apparatus for preparation of monooxidized products from carbohydrates, carbohydrate derivatives and primary alcohols, German Patent DE 4307388 (1994) Chem. Abstr., 122 (1994) 56411q. 

Considerable work was done to induce chirality via chiral auxiliaries. Reac tions with aromatic a-ketoesters like phenylglyoxylates 21 and electron-rich al kenes like dioxoles 22 and furan 23 were particularly efficient (Scheme 6). Yield up to 99% and diastereoselectivities higher than 96% have been observed whet 8-phenylmenthol 21a or 2-r-butylcyclohexanol 21b were used as chiral auxiliarie [14-18]. It should be noted that only the exoisomers 24 and 25 were obtained from the reaction of dioxoles 22. Furthermore, the reaction with furan 23 wa regioselective. 24 were suitable intermediates in the synthesis of rare carbohydrate derivatives like branched chain sugars [16], Other heterocyclic compounds liki oxazole 28 [19] and imidazole 29 [20] derivatives as well as acyclic alkenes 3fl 31, and 32 [14,15,21,22] were used as olefinic partners. Numerous cyclohexane derived alcohols [18,21-24] and carbohydrate derivatives [25] were used as chiri... 

From the molecular beam MS of the pyrolysis products of the P/N fractions, a number of phenolic compounds were detected guaiacol (2-methoxyphenol) (m/z 124), catechols (m/z 110), isomers of substituted 2-methoxyphenols with alkyl groups such as methyl (m/z 138), vinyl (m/z 150), 3-hydroxy-propen(l)-yl (m/z 180), allyl (m/z 164), hydroxyethyl (m/z 168), and ethyl (152), most likely in the para position. In addition, a few carbohydrate-derived components are also present in this fraction such as furfuryl alcohol and other furfural derivatives. 

The /V-phenylselenophthalimide (NPSP)-tributylphosphine (Bu3P) system is also a useful reagent for the facile transformation of carboxylic acids into seleno esters, and of alcohols into alkyl phenyl selenides (including some carbohydrate derivatives).102 The utility of iV-phenylselenophthalimide (N-PSP) as a selenylating agent has been reviewed by Nicolaou and co-workers.103... 

Additionally, in a carbohydrate-derived synthesis of the oxahydrindene portion of the avermectins, a Swem oxidation was performed on the alcohol (35), demonstrating further the range of functionality that can be accommodated under these conditions. ... 

Several aspects of the MEP pathway reaction sequence are unexpected, including the conversion of two highly oxidized carbohydrate derivatives, pyruvate 9 and glyceraidehyde phosphate 10 (GAP), into two monounsaturated alcohol diphosphates, IPP 7 and DMAPP 8 (Fig. 2). 

Since the complex in which this ligand is coordinated only by carboxylate-0 and amide-N atoms would not be optically active, CD spectroscopy was used to confirm the coordination of the alcoholic OH group on C(2) of the sugar moiety to copper(Il), resulting in the formation of a second chelate ring, beside that between the carboxylate-0 and amide-N donor atoms. Similar extra stabilization was observed in complexes of carbohydrate derivatives of thiazolidine-4-carboxylic acid.2.3 This effect was shown to depend on the conformation of the sugar moiety. 

In carbohydrate trityl ethers and the partially acylated carbohydrate derivatives obtained from them, the free hydroxyl groups may be etheri-fied with other alcohols. This method has been used repeatedly, particularly for the preparation of partially methylated compounds. With the alkali resistant trityl ethers, any alkaline alkylation method may be used, for example, dimethyl sulfate and alkali, or methyl iodide and silver oxide. In choosing an alkylation method for partially acylated compounds, one must be selected which does not cause acyl migration or saponification. 

Alcohol Compounds.—That the carbohydrates are, in fact, alcohol compounds is shown, both by their relation to poly-hydroxy alcohols and by their reactions. Carbohydrates possess alcohol characters in that they undergo distinctly alcoholic reactions. Like all alcohols they react with acetyl chloride or acetic anhydride. In.practice the latter reagent is used. They form acetyl derivatives, or esters, just as ethyl alcohol does. 

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