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Alcohol dehydrogenases (ADHs) are applied in industrial synthetic chemistry for the production of optically active secondary alcohols. However, the substrate spectrum of many ADHs is narrow, and few, for example, are suitable for the reduction of prochiral ketones in which the carbonyl group is bounded by two bulky and/or hydrophobic groups; so-called 'bulky-bulky' ketones. Recently two ADHs, RasADH from Ralstonia sp. DSM 6428, and SyADH from Sphingobium yanoikuyae DSM 6900, have been described, which are distinguished by their ability to accept bulky-bulky ketones as substrates. In order to examine the molecular basis of the recognition of these substrates the structures of the native and NADPH complex of RasADH, and the NADPH complex of SyADH have been determined and refined to resolutions of 1.5, 2.9 and 2.5 Å respectively. The structures reveal hydrophobic active site tunnels near the surface of the enzymes that are well-suited to the recognition of large hydrophobic substrates, as determined by modelling of the bulkybulky substrate n-pentyl phenyl ketone. The structures also reveal the bases for NADPH specificity and (S)-stereoselectivity in each of the biocatalysts for n-pentyl phenyl ketone and related substrates.

COMMUNICATION This journal is © The Royal Society of Chemistry 2012Green Chemistry, 2014, 00, 1-5 | 1 An efficient methodology to oxidize β,β-dihalogenated secondary alcohols employing oxygen was achieved in a biphasic medium using the laccase from Trametes versicolor/TEMPO pair, providing the corresponding ketones in a clean fashion under very mild conditions. Moreover, a chemoenzymatic protocol has been successfully applied to deracemize 2,2-dichloro-1-phenylethanol combining this oxidation with an alcohol dehydrogenase-catalyzed bioreduction.Oxidation of alcohols into the corresponding carbonylic compounds is one of the fundamental reactions in organic chemistry. Traditionally these transformations comprised the use of hazardous metal-based reagents in stoichiometric amount, however catalytic methodologies employing oxygen (or air) as mild oxidant in aqueous medium are being recognized for large scale applications, and therefore they are currently emerging as potent competitors.

COMMUNICATIONThis journal is © The Royal Society of Chemistry 2012 J. Name., 2012, 00, 1-3 | 1 are typically accessed by a base-promoted aldol reaction of an -azidoketone 2 and a non-enolizable aldehyde 3 3 (Scheme 1). Scheme 1Although these protocols render the aldol aducts 1 with optimum chemical yield, undesired mixtures of anti and syn isomers are always present. In fact, to our knowledge, there are no methodologies described in the literature that allow gaining access to -azido--hydroxy ketones 1 in a controlled diastereo-and enantioselective manner. Proline is the most popular organocatalyst. This naturally occurring amino acid is cheap, readily available in both enantiomeric forms, and can be used for a wide range of synthetic transformations. 6 Aiming to avoid the use of other synthetically elaborated organocatalysts, our group, 4 and others, 7 have demonstrated how the addition of additives can enhance the reactivity and selectivity of this off-the-bench catalyst in classical transformations such as the aldol reaction. Moreover, the addition of additives can also expand the boundaries of proline as catalyst. In this sense, we have reported the first proline-catalyzed asymmetric synthesis of chlorohydrins through the intermolecular aldol reaction between chloroacetone and aromatic aldehydes, made feasible by the participation of a guanidinium salt as an additive. Motivated by our previous results, we decided to explore the behaviour of our catalytic guanidinium salt/proline system towards a reaction like that illustrated in Scheme 1. 4-Nitrobenzaldehyde, 4a, was adopted as the model substrate for preliminary reactions. Azidoacetone (5, 1-azidopropan-2-one) was prepared in multi-gram scale, in 96% yield, from chloroacetone and sodium azide. In correspondence with our previous work, we decided to evade the use of any organic solvent, apart from ketone 5, which acts as both reagent and reaction media.8 A careful optimization of the stoichiometries involved in the reaction, time, temperature, as well as the judicious choice of the anion accompanying the guanidinium salt, revealed ideal conditions (see Supporting Information (SI) for details, Tables S1-S5). So, when a suspension of (S)-proline (10 mol%), guanidinium salt 6 (15 mol%) and 4-nitrobenzaldehyde 4a, in a moderate excess of azidoacetone 5

The steroid prodrug OPN-501 has optimal drug release characteristics for colon targeting because of a kinetic advantage of a six-membered ring formation in the aminolysis reactions of anilides. The results are relevant to the development of OPN-501 but also to cyclization strategies in prodrug design especially for colon targeting.