The authors report the enhancement of the bandgap emission from ZnO thin films by surface modification and surface plasmon cross-coupling. 12-fold and twofold enhancements of bandgap emission from the metal side of ZnO film were observed by sputtering Pt nanopattern and Pt film onto ZnO film, respectively. Time-resolved photoluminescence indicates that the decay time is slowed down by Pt capping, contrary to common observations. The "abnormal" phenomena are interpreted by considering both the surface modification and surface plasmon coupling.

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S)-N-Boc-3-hydroxypiperidine (S-NBHP) is a useful synthon for the synthesis of pharmaceutical intermediates including ibrutinib, the API of the newly approved drug Imbruvica, for the treatment of lymphoma. To our knowledge, there are no published biotransformation methods scalable to prepare S-NBHP. We report here the development of an efficient process catalyzed by recombinant ketoreductase (KRED) to reduce N-Boc-piperidin-3-one to obtain optically pure S-NBHP. The process has been optimized and demonstrated to have commercial potential with 100 g/L of substrate concentration, product of >99% ee with under 5% of enzyme loading (w/w). ■ INTRODUCTIONA large number of natural and unnatural bioactive molecules have one or more piperidine rings. 1 There are many active pharmaceutical ingredients (API) which also contain this moiety. 2 The hydroxyl group on the C3-position would introduce a chiral carbon atom and may significantly affect the bioactivity of the molecule. 3 As a result, chiral hydroxypiperidines and their derivatives are important synthons used in the pharmaceutical industry.Several methods have been reported for the synthesis of chiral piperidines including classic diastereomeric resolution, 4 asymmetric synthesis, 5 and asymmetric reduction, for example, of 4-oxo-piperidine-3-carboxylic acid esters followed by multistep conversions (Scheme 1). 6 All these methods suffered from low yields or lengthy synthesis. Lacheretz et al. reported the bioreduction of cyclic 3-oxo-amines using the tissue of Daucus carota, where six piperidin-3-one derivatives could be reduced to S-alcohols with varying enantioselectivity. 7 Among the substrates, the reduction of N-Boc-piperidin-3-one showed the highest enantioselectivity, giving (S)-N-Boc-3-hydroxypiperidine (S-NBHP) with 95% optical purity. Unfortunately the reaction is not practical due to low substrate concentration (3 mM), high catalyst concentration (23%, m/v), moderate chiral purity (95% ee) and low yield (73%).Ketoreductase (KRED)-mediated biotransformation has been applied more and more widely in pharmaceutical industry nowadays. 8 In general, there are two strategies to locate a KRED for practical application. On the one hand, the discovery of new natural KRED biocatalysts using activity screening and genome mining continues to enlarge the substrate spectrum. 9 On the other hand, enzyme engineering technologies including directed evolution and semirational and rational design can engineer KREDs with high efficiency and stability. 10 Directed evolution and rational design as the most important technique of protein engineering have emerged to be powerful tools for manipulating protein properties with numerous successful stories. 11 The availability of highly diversified KRED libraries makes it increasingly possible to discover biocatalysts to meet the metrics of industrial processes. Here we report such a work to screen and apply recombinant KREDs to catalyze the asymmetric preparation of S-NBHP on an industrial scale. ■ RESULTS AND DISCUSSIONThe target enz...

A facile and general method for constructing carbon–heteroatom (C–P, C–O, C–S, and C–N) bonds via C–N cleavage of benzyl ammonium salts under transition-metal-free conditions was reported. The combination of t-BuOK and 18-crown-6 enabled a wide range of substituted benzyl ammonium salts to couple readily with different kinds of heteroatom nucleophiles, i.e. hydrogen phosphoryl compounds, alcohols, thiols, and amines. Good functional group tolerance was demonstrated. The scale-up reaction and one-pot synthesis were also successfully performed.

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