Cyanohydrin formation, enzymatic

Table 1. ( )-Cyanohydrins by Enzymatic Formation from Aldehydes and Hydrocyanic Acid 14,15...

Table 3. (R)-Cyanohydrins by Enzymatic Formation from Ketones and Hydrocvamic Acid as well as (7 )-a-Hydroxy-a-methyl Carboxylic Acids by Hydrolysis...

Table 7.2 Enzymatic formation of cyanohydrins from aldehydes (Griengl, 2000).

A classical method for controlling the stereoselectivity of intramolecular nitrone cycloadditions is to have a chiral center located on the chain between the nitrone and the alkene moiety (175-222). In a few other cases, the chirality is located outside the formed ring system (223-229). Marcus et al. (230) recently described an intramolecular 1,3-dipolar cycloadditions of the 5-aIkenyl- and 6-aIkenylnitrones 124 and 127 (Schemes 12.42 and 12.43). The chiral starting material 123 was obtained in 97% ee from an enzymatic cyanohydrin formation. Subsequent... 

Griengl, H., Hickel, A., Johnson, D.V., Kratky, C., Schntidt, M. and Schwab, H. (1997) Enzymatic cleavage and formation of cyanohydrins a reaction of biological and synthetic relevance. Chem. Commun., 1997,1933-1940. 

Figure 9.2 Enzymatic cyanohydrin formation. R = aryl, alkyl, cycloalkyl, heteroaryl.

Pyrethroids are commercially important insecticides that usually contain a cyclopropyl unit that is m-substituted and a cyanohydrin derivative. They are usually sold as a mixture of isomers. However, asymmetric routes have been developed, especially because these compounds are related to chrysanthemic esters (Chapter 12).251 The pyrethroids can be resolved through salt formation or by enzymatic hydrolysis.252... 

Scheme 4.107 Enzymatic cyanohydrin formation catalyzed by HNL [429] (MTBE methyl-tert-butyl ether (R)-PaHNL (R)-hydroxynitrile lyase originating from Primus amygdalus (S)-HbHNL (S)-hydroxynitrile lyase originating from Hevea brasiliensis).

Cyanohydrins are versatile building blocks that are used in both the pharmaceutical and agrochemical industries [2-9]. Consequently their enantioselective synthesis has attracted considerable attention (Scheme 5.1). Their preparation by the addition of HCN to an aldehyde or a ketone is 100% atom efficient. It is, however, an equilibrium reaction. The racemic addition of HCN is base-catalyzed, thus the enantioselective, enzymatic cyanide addition should be performed under mildly acidic conditions to suppress the undesired background reaction. While the formation of cyanohydrins from aldehydes proceeds readily, the equilibrium for ketones lies on the side of the starting materials. The latter reaction can therefore only be performed successfully by either bio- or chemo-cat-... 

Scheme 19 Enzymatic cyanohydrin formation in a continuous flow process...

A fascinating variant of the enzymatic cyanohydrin formation consists in the use of nitroalkanes (as nonnatural nucleophiles) instead of cyanide (Scheme 2.209) [1568,1569]. Overall, this constitutes a biocatalytic equivalent to the Henry-reaction producing vicinal nitro-alcohols, which are valuable precursors for amino alcohols. Using (5)-HNL, the asymmetric addition of nitromethane to benzaldehyde gave the nitroalcohol in 92% e.e., while for p-nitrobenzaldehyde the stereoselectivity dropped sharply. With nitroethane, two stereocenters are created Whereas the stereoselectivity for the alcoholic center was high (e.e. 95%), the recognition for the adjacent center bearing the nitro moiety was modest and other (dia)stereomers were formed in up to 8%. 

One of the major issues that need to be controlled is the nonspecific chemical addition of HCN to the substrate, which negatively impacts the enantiopurity of the product, as enantiopurity is the result of the ratio of enzymatic to nonenzymatic cyanohydrin formation. This nonenz3unatic background reaction is pH and temperature dependent performing the conversions at low pH values (<4-5) and low temperature (5-8 °C) allows the suppression of the xmdesired racemic product formation, thereby enabling the synthesis of cyanohydrins with higher enantiopurity. However, as an aqueous... 

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