Carbohydrates nitriles

The application of the immobilized nitrilase SP 409 of Rhodococcus sp. from Novo Industri (Denmark), which covers a wide substrate spectrum of aliphatic, aromatic, het-erocylic, and carbohydrate nitriles, proved to be synthetically viable for the mild and stereoselective transformation of base-sensitive carbohydrate nitriles [39]. Preferentially the P anomer of a diastereomeric glycosyl cyanide was hydrolyzed to the corresponding acid (Fig. 8). Using a C-7 alkoxylated glycosyl cyanide, amide intermediates were also detected, indicating the additional presence of a nitrile hydratase. 

The removal of the carbohydrate auxiliary group and the hydrolysis of the amino nitriles is achieved by acidolytic cleavage of the hemiaminal /V-glycosidic bond and the concomitant acid-catalyzed solvolysis of the nitrile using either hydrogen chloride in formic acid or hydrogen bromide in acetic acid56 57. 

The introduction of electronic asymmetry into this class of bis(diaryl)phosphinites has been used to design catalysts that can afford both enantiomers of naproxen nitrile. If the carbohydrate scaffold is based on methyl o-D-fructol uranosidc (29), (i )-naproxen nitrile is produced. In a similar manner to the results above, electron-donating aryl substituents on phosphorus afford... 

This chapter, therefore, ends the monograph with a potpourri of reactions all of which occur without a change in oxidation state. In many cases, the reaction is one of nucleophilic attack at an electrophilic C-atom. The result is often hydrolytic bond cleavage (e.g., in carbohydrate conjugates, disubstitut-ed methylene and methine groups, imines, oximes, isocyanates, and nitriles, and various ring systems) or a nucleophilic substitution (e.g., hydrolytic de-halogenation of halocarbons and chloroplatin derivatives, and cyclization reactions). The formation of multiple bonds by dehydration is a special case to be discussed separately. 

Hydrolysis can detoxify a wide range of aliphatic and aromatic organics such as esters, ethers, carbohydrates, sulfonic acids, halogen compounds, phosphates, and nitriles. It can be conducted in simple equipment (in batches in open tanks) or in more complicated equipment (continuous flow in large towers). However, a potential disadvantage is the possibility of forming undesirable reaction products. This possibility must be evaluated in bench- and pilot-scale tests before hydrolysis is implemented. 

Optically active aldehydes are available in abundance from amino and hydroxy acids or from carbohydrates, thereby providing a great variety of optically active nitrile oxides via the corresponding oximes. Unfortunately, sufficient 1,4- or 1,3-asymmetric induction in cycloaddition to 1-alkenes or 1,2-disubstituted alkenes has still not been achieved. This represents an interesting problem that will surely be tackled in the years to come. On the other hand, cycloadditions with achiral olefins lead to 1 1 mixtures of diastereoisomers, that on separation furnish pure enantiomers with two or more stereocenters. This process is, of course, related to the separation of racemic mixtures, also leading to both enantiomers with 50% maximum yield for each. There has been a number of applications of this principle in synthesis. Chiral nitrile oxides are stereochemicaUy neutral, and consequently 1,2-induction from achiral alkenes can fully be exploited (see Table 6.10). 

Intramolecular 1,3-dipolar additions of nitrones and nitrile oxides to carbohydrate alkene groups have met with success. Thus, treatment of the unsaturated heptose ether 68 (Scheme 17), which can be made following 1,3-dithianyl anion addition to C-l of 2,3,4-tri-0-benzyl-5,6-dideoxy-D-xy/o-hex-5-enose, with IV-methylhydroxylamine in refluxing methanol, affords the nitrone 69 that cyclizes to give the bicyclic isoxazolidine 70 (60% isolated) together with the epimer at the new asymmetric center carrying the methylene carbon atom (16% isolated) [35]. 

The reaction accommodates halides, esters, ethers, nitriles, cyclopropanes, epoxides, alcohols and nitio groups. Even carbohydrates can be used.492-494 However, vinylic halides afford aldehydes and ketones... 

Potassium cyanide has been caused to react with salts and esters of sulfonic acids to give nitriles. Thus, an intimate mixture of finely powdered potassium cyanide with the compound may be fused 422 this method was successfully applied428 to tetrahydrofurfuryl p-toluenesul-fonate and methanesulfonate, but failed with l,2 3,4-di-0-isopropylidene-6-O-tosyl-D-galactose. Another method, consisting of treatment of the ester with a stirred, boiling, saturated, aqueous solution of potassium cyanide gave885 a 70 to 83% yield of nitrile with primary p-toluenesul-fonates (ethyl, n-butyl, and n-octyl) and a 43% yield with a secondary p-toluenesulfonate (isopropyl). Similar methods had been applied earlier98 841 to such simple esters, but have not apparently found use with sulfonic esters of carbohydrates. 

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. 

RajanBabu and Casalnuovo [19, 20] tested diphosphinite ligand systems (5 and 6 in Figure 4) based on carbohydrate backbones. The steric and electronic properties depended on the substituents on the aryl groups on the phosphorus atoms. The use of different chlorophosphine precursors led to the electronically asymmetric ligand 6. This approach resulted in both enantiomers of naproxen nitrile from MVN in 91 % ee (S)-nitrile (ligand 5) and 95 % ee (R)-nitrile (ligand 6) at 0 °C. 

The chiral induction of carbohydrate enol ethers in 1,3-DC with some aromatic nitrile oxides was investigated. The highest diastereoseletivity (28 1 dr) was achieved with a 3-0-vinyl-p-D-fructopyranose derivative and 2,4,6-trimethylbenzonitrile oxide <02TA2535>. 

Palladium on barium sulfate, Pd/BaS04 Acts as a hydrogenation catalyst for nitriles in the Kiliani-Fischer chain-lengthening reaction of carbohydrates (Section 25.6). 

Chiral dipolarophiles such as 43 <03TL1071> and 45 <03SL1358>, derived from carbohydrates, react with nitrile oxides to afford spiro- and bicyclic-isoxazolines 44 and 46, respectively, with high regio- and diastereoselectivity. 

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