Aldehyde biological reduction

NADH (reduced nicotinamide adenine dinucleotide) is utilized in biological reductions to deliver hydride to an aldehyde or ketone carbonyl group (see Box 7.6). A proton from water is used to complete the process, and the product is thus an alcohol. The reaction is catalysed by an enzyme called a dehydrogenase. The reverse reaction may also be catalysed by the enzyme, namely the oxidation of an alcohol to an aldehyde or ketone. It is this reverse reaction that provides the dehydrogenase nomenclature. 

Figure 3-23. Representation of the hydride transfer reaction involved in the biological reduction of aldehydes to alcohols.

A third method of aldehyde synthesis is one that we ll mention here just briefly and then return to in Section 21.6. Certain carboxylic acid derivatives can be partially reduced to yield aldehydes. The partial reduction of an ester by dhsobutylaluminum hydride (DIBAH), for instance, is an important laboratory-scale method of aldehyde synthesis, and mechanistically related processes also occur in biological pathways. The reaction is normally carried out at —78 °C (dry-ice temperature) in toluene solution. 

Figure 19.15 Mechanism of biological aldehyde and ketone reductions by the coenzyme NADH.

The aldehyde intermediate can be isolated if 1 equivalent of diisobutvl-aluminum hydride (D1BAH) is used as the reducing agent instead of LiAlH4. The reaction has to be carried out at -78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or acyl phosphate rather than an ester. 

The widespread occurrence and biological significance of polyoxygenated carbocycles provided the impetus to apply RCM to sugar-derived dienes. Carbohydrate carbocyclization based on a sequence of Vasella reductive opening of iodo-substituted methyl glycosides [25], and RCM of the dienes available from the resulting unsaturated aldehydes, were used to prepare a series of natural compounds (Schemes 5-7). 

The reduction of ketones, aldehydes, and olefins has been extensively explored using chemical and biological methods. As the latter method, reduction by heterotrophic microbes has been widely used for the synthesis of chiral alcohols. On the contrary, the use of autotrophic photosynthetic organisms such as plant cell and algae is relatively rare and has not been explored because the method for cultivation is different from that of heterotrophic microbes. Therefore, the investigation using photosynthetic organisms may lead to novel biotransformations. 

After phytochemical reduction was noted in the case of aldehydes and ketones, interest arose in the behavior of fermenting cells toward compounds containing several carbonyl groups per molecule, such as diketones and quinones. This class deserves special consideration because the simplest representative, diacetyl, as well as its products of reduction, acetylmethylcarbinol (3-hydroxybutanone) and 2,3-butylene glycol, are connected with the metabolism of numerous cells quinones also are biologically important. 

Immobilization by reductive amination of amine-containing biological molecules onto aldehyde-containing solid supports has been used for quite some time (Sanderson and Wilson, 1971). The reaction proceeds with excellent efficiency (Domen et al., 1990). The optimum pH for the reaction is alkaline, although good yield can be realized from pH 7—10. At high pH (9—10) the formation of the Schiff bases is more efficient and the yield of conjugation or immobilization reactions can be dramatically increased (Hornsey et al., 1986). 

In these compounds, there is a marked relationship between molecular geometry and biological activity. From values reported in the literature and according to our own studies, the E isomers, in which the residue originating from the aldehyde is in the transposition to the triazole, are markedly superior to the Z isomers in their biological activity. By suitable control of the reaction conditions, it is possible to achieve an almost complete isomerization to the unsaturated E-triazolylketones. Subsequent reduction leads to the more active E-alcohols. This group of N-vinylazoles includes the triazole derivative S 3308 (Sumitomo), currently under development as... 

Reactions of Aldehydes and Ketones Aldehydes and ketones are central players in organic synthesis because of the wide variety of reactions they undergo. Likewise, their chemistry is important to biological systems. We will consider just two of the reactions involving these compounds oxidation/reduction and formation of acetals and ketals. 

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