Dalcetrapib (1), a cholesterol ester transfer protein inhibitor, was a clinical candidate at Roche until 2012. By this time, manufacturing processes capable of efficiently delivering kilotonne annual volumes of Dalcetrapib had been developed and demonstrated at the commercial scale. This paper describes the development of synthetic routes for the manufacture of key intermediate 1-(2-ethylbutyl)-cyclohexanecarboxylic acid (2) and selection of the preferred process. The selected process involves novel methods for the α-alkylation of a nitrile using methylmagnesium chloride as a non-nucleophilic base and for the hydrolysis of a highly sterically hindered nitrile using sodium hydroxide in methanol/water at 200 °C. The performance of the process at plant scale is reported. Safety considerations and the chemistry behind the formation of side-products are discussed. Continuous-flow processes with potential operational benefits were demonstrated at laboratory scale for both the alkylation and the nitrile hydrolysis steps. A possible second-generation process for the manufacture of acid 2 is also described, which involves a novel reductive alkylation of benzoic acid.

Nuclear magnetic resonance (NMR) spectroscopy is an analytical tool to determine the structure of chemical compounds. Unlike other spectroscopic methods, signals recorded using NMR spectrometers are frequently in a range of zero to 20000 Hz, making direct playback possible. As each type of molecule has, based on its structural features, distinct and predictable features in its NMR spectra, NMR data sonification can be used to create auditory ‘fingerprints’ of molecules. This paper describes the methodology of NMR data sonification of the nuclei nitrogen, phosphorous, and oxygen and analyses the sonification products of DNA and protein NMR data. The paper introduces On the Extinction of a Species, an acousmatic music composition combining NMR data sonification and voice narration. Ideas developed in electroacoustic composition, such as acousmatic storytelling and sound-based narration are presented and investigated for their use in sonification-based creative works.

Molecular sonification is the transformation of chemical data into sound and has been used to gain insight into chemical systems and for the creation of contemporary music compositions. The combination of sonification with a virtual reality environment offers potential benefits such as providing a visual frame of reference, an increased sense of immersion, nuanced spatial information through binaural audio cues and ease of interactivity. To explore how strategies developed in sonification research and contemporary electroacoustic music composition can be adapted to virtual reality, the art-science installation 'Quantum' was created. The multi-media work consists of computer-generated molecules in a virtual space producing sound created via the sonification of nuclear magnetic resonance data. Upon user interaction with different molecules, the overall composition and complexity of the sound world develop. The binaural sound material can migrate back and forth from the molecules to the non-binaural background composition and, depending on user input, develop in terms of timbre, spectral complexity, and gestural content. 'Quantum' is an exploration of the combination of sonification and virtual reality and offers first points of discussion that can be elaborated upon in future artworks, games or educational content.

Ringing the changes: Selenazolines have applications in medicinal chemistry, but their synthesis is challenging. We report a new convenient and less toxic route to these heterocycles that starts from commercially available selenocysteine. The new route depends on a heterocyclase enzyme that creates oxazolines and thiazolines from serines/threonines and cysteines.

ChemistryOpenVolume 2, Issue 2 p. 46-49 NewsOpen Access Spotlights on our sister journals: ChemistryOpen 2/2013 First published: 23 April 2013 https://doi.org/10.1002/open.201390009AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume2, Issue2April 2013Pages 46-49 RelatedInformation

Pyrimidine alkynes can be transformed into the corresponding annulated pyridines efficiently in flow. The superheating of organic solvents far beyond their boiling point enables toxic and difficult to workup solvents such as nitrobenzene or chlorobenzene, which are usually employed for these reactions, to be replaced by less harmful ones like toluene. The relative rate of reactivity for a series of structurally close starting materials was investigated and a scalable flow process was developed, providing facile access to a series of novel annulated pyridine building blocks. The effect of thermal volume expansion of solvents under superheated conditions was found to be significant and influenced the residence times considerably. To obtain meaningful and accurate residence times, flow rates need to be corrected for volume expansion. To avoid confusion with residence times, t(R), calculated from nominal flow rates, we would propose to use for such corrected residence times the term effective residence time, t(R,eff).

Peptide macrocycles are found in many biologically active natural products. Their versatility, resistance to proteolysis and ability to traverse membranes has made them desirable molecules. Although technologies exist to synthesize such compounds, the full extent of diversity found among natural macrocycles has yet to be achieved synthetically. Cyanobactins are ribosomal peptide macrocycles encompassing an extraordinarily diverse range of ring sizes, amino acids and chemical modifications. We report the structure, biochemical characterization and initial engineering of the PatG macrocyclase domain of Prochloron sp. from the patellamide pathway that catalyzes the macrocyclization of linear peptides. The enzyme contains insertions in the subtilisin fold to allow it to recognize a three-residue signature, bind substrate in a preorganized and unusual conformation, shield an acylenzyme intermediate from water and catalyze peptide bond formation. The ability to macrocyclize a broad range of nonactivated substrates has wide biotechnology applications.