Biological reaction, alcohol ketone 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. 

The pioneering studies by Itsuno [1] and Corey [2] on the development of the asymmetric hydroboration of ketones using oxazaborolidines have made it possible to easily obtain chiral secondary alcohols with excellent optical purity [3]. Scheme 1 shows examples of Corey s (Corey-Bakshi-Shibata) CBS reduction. When oxazaborolidines 1 were used as catalysts (usually 0.01-0.1 equiv), a wide variety of ketones were reduced by borane reagents with consistently high enan-tioselectivity [2]. The sense of enantioselection was predictable. Many important biologically active compounds and functional materials have been synthesized using this versatile reaction [2-4]. 

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

Life uses enzymes to catalyse asymmetric reactions, so the question is—can chemists The answer is yes, and there are many enzymes that can be produced in quantities large enough to be used in the catalytic synthesis of enantiomerically pure molecules. This field—known as biocatalysis—melds ideas in chemistry and biology, and we do not have the space here to discuss it in detail. We leave you with just one example the reduction of a ketone to an alcohol with an enzyme known as a ketoreductase. 

Aldehydes and ketones are among the most important of all compounds, both in the chemical industry and in biological pathway. In this chapter, we ve looked at some of their typical reactions. Aldehydes are normally prepared in the laboratory by oxidation of primary alcohols or by partial reduction of esters. Ketones are prepared by oxidation of secondary alcohols. 

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