Cyanohydrins naturally occurring

Naturally occurring compounds called cyanogenic glycosides, such as lotau-stralin, release hydrogen cyanide, HCN, when treated with aqueous acid. The reaction occurs by hydrolysis of the acetal linkage to form a cyanohydrin, which then expels HCN and gives a carbonyl compound-fa) Show the mechanism of the acetal hydrolysis and the structure of the cyanohydrin that results. 

For the synthesis of cyanohydrins nature provides the chemist with R- and S-selective enzymes, the hydroxynitrile lyases (HNL) [4-7]. These HNLs are also known as oxynitrilases and their natural function is to catalyze the release of HCN from natural cyanohydrins like mandelonitrile and acetone cyanohydrin. This is a defense reaction of many plants. It occurs if a predator injures the plant cell. The reaction also takes place when we eat almonds. Ironically the benzaldhyde released together with the HCN from the almonds is actually the flavor that attracts us to eat them. 

Although the cyanohydrin is an uncommon functional group, linamarin and amygdalin are two naturally occurring cyanohydrin derivatives. Both contain a carbon atom bonded to both an oxygen atom and a cyano group, analogous to a cyanohydrin. 

Naturally occurring cyanohydrin derivatives—linamarin, from cassava root and amygdahn, commonly called laetrile, from apricot, peach and wild cherry pits (Section 21.9B)... 

The higher-carbon sugars formed the subject matter of the first review to appear in this Series on that occasion, particular attention was devoted to the Fischer cyanohydrin synthesis which, until 1942, had been the only method available for preparing these sugars. Since that time, considerable advances have been made in the field of the higher sugars, notably in the development of new synthetic methods and in determination of the role played by heptoses, especially sedoheptulose, in natural systems. Moreover, the recently reported isolations of the first naturally occurring... 

Gynocardin is a naturally occurring cyanogenic glycoside having the structure shown. What cyanohydrin would you expect to be formed on hydrolysis of gynocardin, and to what ketone does this cyanohydrin correspond ... 

P,7-Unsaturated ethers of cyanohydrins, on formation of lithio derivatives, undergo a 2,3-sigmatropic rearrangement to form. y-unsaturated ketones (equation 21), whereas benzylic ethers of aliphatic cyanohydrins gave o-methylaryl ketones. The method has been used to prepare 3-methyi-l-(3-methyl-2-furyl)-l-butanones, a naturally occurring Cio terpene, a-allenic ketones and enolic monoethers of 7-keto aldehydes via 2,3-sigmatropic rearrangement of tiieir respective carbanions. ... 

Biosynthesis of linamarin and lotaustralin has been studied by Conn et al. (19, 149). On the basis of highly effective incorporation of " C-labelled L-valine into linamarin and of L-isoleucine into lotaustralin, they concluded that these amino acids are precursors of the two cyanoglucosides. Since the glucosyl transferase (UDP-glucose ketone cyanohydrin-yff-D-glucosyltransferase) was shown to be unable to distinguish between the two possible enantiomers - (i ,S)-2-hydroxy-2-methyl-butyro-nitriles - L-isoleucine ([3S]-Ls-isoleucine), which supplies the / -enantiomer, must be the sole precursor for naturally occurring (/ )-lotaustralin (149). It is quite possible that L-leucine is the precursor of acacipetalin, proacacipetalin, epiproacacipetalin, and cardiospermin. 

This strategy has been exploited in the synthesis of variety of naturally occurring compounds such as pheromones and steroids." For example, selective elimination of the aeetate moiety from cyanohydrin derivative 95 was used to prepare key intermediate 96. Diene 96 was subsequently elaborated to pellitorine (97). ... 

A few cyanohydrins and ethers of cyanohydrins occur naturally One species of millipede stores benzaldehyde cyanohydrin along with an enzyme that catalyzes its cleavage to benzaldehyde and hydrogen cyanide m separate compartments above its legs When attacked the insect ejects a mixture of the cyanohydrin and the enzyme repelling the invader by spraying it with hydrogen cyanide... 

This example (the cyanohydrin reaction) appears to me to provide a simple solution for the natural asymmetric synthesis. The formation of the sugar, as the plant physiologists assume, occurs in the chlorophyll grain, which itself is composed of optically active substances.. . . The prepared sugar is released and later on used by the plant, as is known, for the preparation of other organic components. Their asymmetry is thus explainedfrom the nature of the building material. Of course, they also provide material for new chlorophyll... 

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). 

Takahashi and coworkers have employed intramolecular reactions of anions of unsaturated protected cyanohydrins to produce unsaturated carbocyclic systems containing 10-, 14- and 16-membered rings which are convertible into natural products. These reactions occur regiospecifically at the a-position and usually do not involve ( ) — ( isomerization of P,7-double bonds. The preparation of 2-cyclopen-tadecenone (155), which is convertible into the macrocyclic perfumes muscone and exaltone, is illustrative of this methodology (Scheme 76). 

This intermediate is similar in nature to the cyanohydrin product that is formed by the addition of a cyanide anion to a carbonyl compound. However, in the latter case, no further reaction may occur, yet in this case there is the potential for further reaction. Suggest what are the next steps, and what is the final product. 

Cyanohydrin formation, being reversible and occurring in nature, is relevant to the potential hazards from ingesting cyanohydrins. Thus, Prunus amygdalus dulcis is a source of an oil used in confectionery. However, when crushed, the kernels of Prunus amygdalus amara yield an oil commonly known as oil of bitter almonds (oleum amygdalae amarae). On hydrolysis, the latter produces as much as 6% of hydrogen cyanide (http //en.wrkipedia.org). 

Fisher s oxazole formation occurs by the condensation of cyanohydrins with aldehydes in the presence of HCl in dry ethereal solution. The cyanohydrins and aldehydes used are usually aromatic in nature, although there are aliphatic examples that have been reported. There has been little study of the reaction mechanism such as that shown by Ingham and Comforth in the early nineteenth century the reaction details have also been published by others. " The first step of the mechanism is the addition of HCl to the cyanohydrin to from an iminochloride intermediate 2. This intermediate then reacts with the aldehyde, which is followed by water loss to give a chloro-oxazoline intermediate 4. Isomerization of two protons occurs, followed by the loss of an HCl molecule to form the 2,5-diaryloxazole end product. 

Cyanohydrins occur naturally, often as derivatives in which the -OH group has been modified to -OR, where R is a carbohydrate unit. These cyanogenic glycosides are widespread in plants one, called amygdaiin, is found in bitter almonds and in the kernels of peaches, plums, apricots, and related fruits. 

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