TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 12 (2001) 3119–3123 Pergamon Stereospecificity of hydride transfer during the dismutation of aldehydes catalyzed by alcohol dehydrogenases K. Velonia and I. Smonou* Department of Chemistry, University of Crete, 71 409 Heraklio, Crete, Greece Received 19 October 2001; accepted 4 December 2001 Abstract—The stereochemistry of the oxidation of aldehydes to acids with alcohol dehydrogenases was studied with respect to the selectivity towards the cofactor. © 2002 Published by Elsevier Science Ltd. 1. Introduction The stereoselectivity in the oxidation of alcohols to the corresponding ketones or aldehydes and the reduction of these carbonyl compounds to the corresponding alcohols with alcohol dehydrogenases (ADHs) has been well established through numerous reports in the litera- ture. 1–5 While it was previously thought that aldehydes are not substrates for oxidative reactions, it has recently been shown that ADHs can also catalyze the dismuta- tion of aldehydes to the corresponding alcohols and carboxylic acids. 6 One of the main factors which determine the selectivity of ADH-catalyzed transformations is the stereospecific- ity of hydride transfer to and from C(4) of the nicoti- namide ring of the NAD(H) cofactor. With respect to this specificity, ADHs have been classified into two types: Type A enzymes which catalyze hydride transfer to the re face of the cofactor and Type B enzymes which do so to the si face. Herein, we report our stereochemical studies on the oxidation of aldehydes to acids with ADHs with respect to the selectivity towards the cofactor and we compare this selectivity to that determined for the oxidation of alcohols by the same enzymes. 2. Results and discussion The dismutation of aldehydes, according to the mecha- nism proposed by Oppenheimer 7 (Fig. 1), suggests that the overall reaction consists of two parallel paths: the oxidation of the aldehyde, which releases the corre- sponding carboxylic acid and the reduction of a second Figure 1. Proposed mechanism for the ADH-catalyzed dismutation of aldehydes. * Corresponding author. Tel.: +30-81-393610; fax: +30-81-393601; e-mail: smonou@chemistry.uoc.gr 0957-4166/01/$ - see front matter © 2002 Published by Elsevier Science Ltd. PII:S0957-4166(01)00551-1