Lactones cyanohydrins

Fischer s original method for conversion of the nitrile into an aldehyde involved hydrolysis to a carboxylic acid, ring closure to a cyclic ester (lactone), and subsequent reduction. A modern improvement is to reduce the nitrile over a palladium catalyst, yielding an imine intermediate that is hydrolyzed to an aldehyde. Note that the cyanohydrin is formed as a mixture of stereoisomers at the new chirality center, so two new aldoses, differing only in their stereochemistry at C2, Tesult from Kiliani-Fischer synthesis. Chain extension of D-arabinose, for example, yields a mixture of D-glucose and o-mannose. 

As early as 1917, it was known that C2 and C3 in this trimethyl sugar each carried a methoxyl group, since (a) it failed to yield an osazone, and (b) the trimethyl-D-glucoheptonic acid derived from it by a cyanohydrin synthesis gave a lactone only with the concomitant loss of one of the methyl radicals.135 The production of a dimethyl- and not a trimethyl-... 

A short synthesis of D-gulono-1,4-lactone (2) from the inexpensive and readily available D-xylose (34) was first reported by Fischer and Stahel,18 and subsequently by others,12,25-31 and is shown in Scheme 6. The addition of hydrogen cyanide to D-xylose (34) resulted in the formation of cyanohydrins 35 and 36 which, on hydrolysis, afforded a mixture of D-gulonic acid (4) and D-idonic acid (37). D-Gulono-1,4-lactone may be obtained in 30-33% yield by recrystallization of the reaction products. In a similar way, L-xylose (l-34) has been converted32,33 in high yield into a mixture of L-gulonic and L-idonic acids. 

The cyanohydrin synthesis has been applied in the study of the sugars by H. Kiliani, who used it in the synthesis of higher members of the class. The carboxylic adds which result from the hydrolysis of the nitriles can be reduced, in the form of their lactones, to the corre-... 

L-Mannitol does not occur naturally but is obtained by the reduction of L-mannose or L-mannonic acid lactone (80). It can be synthesized from the relatively abundant L-arabinose through the L-mannose and L-glucose cyanohydrins, conversion to the phenylhydrazines which are separated, liberation of L-mannose, and reduction with sodium borohydride (81). Another synthesis is from L-inositol (obtained from its monomethyl ether, quebrachitol) through the diacetonate, periodate oxidation to the blocked dialdehyde, reduction, and removal of the acetone blocking groups (82). 

If 2-camphanyloxyacrylonitrile (15 R = C8H 02C00) is taken for cycloaddition, diastereoisomeric cycloadducts can be separated, and the basic system, 7-oxabicyclo-[2.2.1]hept-5-en-2-one 17, can be obtained in optically pure form [36]. Another way of obtaining enantiomeric ketones is based on crystallization of a brucine complex obtained from the corresponding cyanohydrines (see Sec. III). Ketone 17 can be converted [e.g., by cis-hydroxylation (—>18), protection of the diol system, and Baeyer-Villiger oxidation] to lactone 19, the opening of which leads to furanuronic acid 20. A new development in this field is based in cycloaddition between furan and 2-chloro- or 2-bromoacrolein in the presence of 5 mol% chiral oxazaborolidine 21 as catalyst [37],... 

Natural D-mannose is the aldehyde of natural D-mannitol, and is transformed by the action of bromine water into D-mannonic acid, which was isolated as its phenylhydrazide. The acid was regenerated from the phenyl-hydrazide and isolated as its crystalline lactone. Kiliani hod obtained the enantiomorph of this lactone on applying the cyanohydrin reaction to natural L-arabinose. A mixture of both lactones formed a racemate. Then, by taking recourse to his newly discovered reduction of the lactones to the aldoses, a reaction which Fischer designated the most significant in the... 

In 1894, Fischer wrote "It will probably be possible to obtain all riiem-bers of the sugar group by a combination of the cyanohydrin reaction with the reduction of lactones, as soon as we have succeeded in finding the two optically active forms of glyceraldchyde. All observations agree with the isomerisms foreseen by Van t Hoff, above all the disappearance of isomers if the molecule becomes constitutionally symmetric. This includes the transformation of different stereoisomers into one and the same substance if one of several asymmetric centers is abolished." An example of this is... 

Ishizu et al.29H found that D-xylose and D-fructose react with aqueous calcium hydroxide to produce 13 lactonizable saccharinic and other acids. These were identified after separation by cellulose column and gas-liquid chromatography, and the Cs-saccharinic acids, 2-C-methyl-D-threonic acid (117) and 2-C-methyl-D-erythronic acid (118), were among those isolated. These authors299 later reported that L-sorbose reacts similarly, to generate 14 lactones, including the 2-C-methyl-L-xr/o o-l,4-lactone and 2-C-methyl-L-lyxono-1,4-lactone, which were also prepared from 1-deoxy-L-threo-pentulose via the cyanohydrin reaction. 

The synthesis of D-psicose as a colorless sirup ([< ]% + 3.1° in water) by Steiger and Reichstein13 may be regarded as the first authentic preparation of this ketohexose. The Kiliani-Fischer cyanohydrin synthesis furnished D-allonic lactone (VII) from D-ribose. This lactone, on reduction with sodium amalgam, gave D-allose (VIII) which was transformed into D-psicose (I) by refluxing with pyridine. Pyridine had been introduced into the Lobry de Bruyn-Van Ekenstein reaction by Fischer, Danilov and their coworkers.13 ... 

By treatment of D-gulose (XVII) or D-idose (XVIII) with warm aqueous barium hydroxide solution Van Ekenstein and Blanksma were able to isolate D-sorbose (II) with a melting point of 165° and [< ]d + 42.9° in water. The aldoses were prepared from D-gulonic and D-idonic lactones obtained by the cyanohydrin synthesis from D-xylose. 

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