Nitriles sugar formation

A different approach involving cyanohydrin formation from the 3-keto sugar was also explored in the D-Fru series (Scheme 17). A mixture of epimeric cyanohydrins was quantitatively formed by reaction with sodium cyanide in methanol, albeit without stereoselectivity. Chromatographic separation of (R)- and (A)-isomers was straightforward and the former epimer was selected to exemplify the two-step transformation into an OZT. Reduction of this nitrile by lithium aluminum hydride led to the corresponding aminoalcohol, which was further condensed with thiophosgene to afford the (3i )-spiro-OZT in ca. 30% overall yield. Despite its shorter pathway, the cyanohydrin route to the OZT was not exploited further, mainly because of the disappointing yields in the last two steps. 

In the case of the oximes of the aldose sugars, the situation is more complicated because of the possibility of both open-chain and cyclic structures. That aldose oximes can react in the open-chain form follows from the formation of the nitriles and from the isolation of acylated open-chain aldose oximes as secondary products in preparation of nitriles. For example, Wolfrom and Thompson, by the action of sodium acetate-acetic anhydride on n-glucose oxime, not only obtained pentaacetyl-D-glucononitrile, in 40% yield, but also isolated a small amount of hexaacetyl-oWeAydo-D-glucose oxime (V) identical with that prepared by mild acetylation of pentaacetyl-aWe%do-D-glucose oxime (IV) whose structure was assured by its formation from pentaacetyl-aldehydo-D-glucoae (III). 

According to Hockett and Chandler, the hydrolysis of an acetylated nitrile (LIII) results in the formation of an acetylated aldehydo sugar (LIV). If this compound then undergoes ammonolysis at carbon atoms 2 or 3, the formation of diacetamides is to be expected, since hemiacetal formation involving the C2 or C3 hydroxyl group is unknown. The... 

Nitrone-Nitrile Oxide Cycloaddition. Unsaturated sugars have been used for the simultaneous formation of carbon-carbon and carbon-oxygen bonds in a cir-relation. One of the best ways to achieve this transformation is the cycloaddition of nitrone or nitrile oxides. The cycloaddition of nitrones with olefins has been reviewed [133]. The regioselec-tivity is almost complete when using activated double bonds, such as enone, enelactone (see compound 98, Scheme 35), or esters. 

A newer technique which shows promise but has not yet been fully tested is based upon the preparation and separation of aldonitrile acetates of reducing sugars (Equation 9.12). The dried sugar is dissolved in pyridine and treated with hydroxylamine hydrochloride in a sealed glass ampoule at 90°C for 0.5 hr. The mixture is cooled, acetic anhydride added, and another 30-min reaction is carried out in the resealed ampoule. Actual formation of the nitrile may occur in the injector of the gas chromatograph. Nonreducing sugars apparently do not form the nitrile but are present as the... 

Primary amine formation is equally well promoted in alkaline medium, e.g., aqueous ethanolic NaOH solution, that selectively poisons the catalyst for hydrogenolysis reactions. However, saturated NH3/alcohol solutions best afford almost quantitative yields of primary amines from catalytic reduction of nitriles. Ammonia adds to imine 1 to give a 1,1-diamine, which is hydrogenolyzed to the primary amine. In the presence of NHj, finely divided Ni can be used, platinized finely divided Ni for the hydrogenation of hindered nitriles, and rhodium-on-alumina for sensitive compounds. Mild reduction of 3-indoleacetonitrile to tryptamine [equation (c)] is effected at RT over 5% rhodium-on-alumina in 10% ethanolic NH3 with little side reaction , and branched chain amino sugars are conveniently prepared using this selective hydrogenation [equation (d)] . 

In addition to the formation of anomeric nitriles, similar chemistry allows for the formation of anomeric isocyanides. Requirements for these reactions include utilizing acetates, halides, and imidates as activating groups. Some Lewis acids used to effect these transformations include SnCU, TMSOTf, TMSCN, Et2AlCN, and HgCN. Additionally, both benzylated and acetylated sugars may be used. 

Of the other stationary phases, the amino phases have been used extensively to separate sugars and peptides the nitrile phase has found application in the separation of porphyrins. An important consideration in the use of polar bonded-phase materials is an awareness of the reactivity of the terminal functional group, for example, aminoalkyl bonded phase should not be used for the chromatography of carbonyl compounds due to possible condensation reactions and formation of Schiff s bases. 

A comprehensive review (260 refs.) on the synthesis of carbohydrates from noncarbohydrate sources covers the use of benzene-derived diols and products of Sharpless asymmetric oxidation as starting materials, Dodoni s thiazole and Vogel s naked sugar approaches, as well as the application of enzyme-catalysed aldol condensations. The preparation of monosaccharides by enzyme-catalysed aldol condensations is also discussed in a review on recent advances in the chemoenzymic synthesis of carbohydrates and carbohydrate mimetics, in parts of reviews on the formation of carbon-carbon bonds by enzymic asymmetric synthesis and on carbohydrate-mediated biochemical recognition processes as potential targets for drug development, as well as in connection with the introduction of three Aldol Reaction Kits that provide dihydroxyacetone phosphate-dependent aldolases (27 refs.). A further review deals with the synthesis of carbohydrates by application of the nitrile oxide 1,3-dipolar cycloaddition (13 refs.). ... 

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