Reactive carbon species tamed for synthesis

The basis of organic chemistry is the study of carbon-containing compounds with the aim of manipulating carbon atoms to generate new molecules through the formation of carbon–carbon (C–C) bonds. In a paper in Nature, Wang et al. report a method for harnessing a reactive form of carbon known as a carbyne (Fig. 1a), which has been underused in synthetic chemistry. The findings open the door to new types of C–C bond-formation reaction

Recent advances in small molecule target identification methods

In this chapter, four major target identification approaches including affinity-based proteomics, in silico target prediction, drug resistance-sequencing, and yeast-based approaches are discussed with demonstrative examples from the last few years. © 2013 Elsevier Inc

Late-stage C-H functionalization of complex alkaloids & drug molecules via intermolecular rhodium-carbenoid insertion

Alkaloids constitute a large family of natural products possessing diverse biological properties. Their unique and complex structures have inspired numerous innovations in synthetic chemistry. In the realm of late-stage C-H functionalization alkaloids remain a significant challenge due to the presence of the basic amine and a variety of other functional groups. Herein we report the first examples of dirhodium(II)-catalyzed intermolecular C-H insertion into complex natural products containing nucleophilic tertiary amines. The application to a diverse range of alkaloids and drug molecules demonstrates remarkable chemoselectivity and predictable regioselectivity. The capacity for late-stage diversification is highlighted in the catalyst-controlled selective functionalizations of the alkaloid brucine

Catalytic Asymmetric Reactions for Organic Synthesis: The Combined C−H Activation/Siloxy-Cope Rearrangement

Tetrakis(N-[4-dodecylbenzenesulfonyl]-(l)-prolinate) dirhodium [Rh2(S-DOSP)4]-catalyzed decomposition of vinyldiazoacetates in the presence of allyl silyl ethers results in the formation of the direct C−H insertion product and the product derived from a combined C−H activation/siloxy-Cope rearrangement. Both products are formed with very high diastereoselectivity (>94% de) and high enantioselectvity (78−93% ee). Under thermal or microwave conditions, the direct C−H insertion product undergoes a siloxy-Cope rearrangement in a stereoselective manner

Catalytic Asymmetric Reactions for Organic Synthesis: The Combined C−H Activation/Siloxy-Cope Rearrangement

Tetrakis(N-[4-dodecylbenzenesulfonyl]-(l)-prolinate) dirhodium [Rh2(S-DOSP)4]-catalyzed decomposition of vinyldiazoacetates in the presence of allyl silyl ethers results in the formation of the direct C−H insertion product and the product derived from a combined C−H activation/siloxy-Cope rearrangement. Both products are formed with very high diastereoselectivity (>94% de) and high enantioselectvity (78−93% ee). Under thermal or microwave conditions, the direct C−H insertion product undergoes a siloxy-Cope rearrangement in a stereoselective manner

A novel luminescence-based high-throughput approach for cellular resolution of protein ubiquitination using tandem ubiquitin binding entities (TUBEs).

Protein turnover is highly regulated by the post-translational process of ubiquitination. Deregulation of the ubiquitin proteasome system (UPS) has been implicated in cancer and neurodegenerative diseases, and modulating this system has proven to be a viable approach for therapeutic intervention. Development of novel technologies that enable high-throughput studies of substrate protein ubiquitination is essential for drug discovery in the UPS. Conventional approaches for studying ubiquitination either require high amounts of starting protein or rely on exogenous or modified ubiquitin moieties and thus limiting their utility. In order to circumvent these issues, we developed a high-throughput live-cell assay which combines the NanoBiT luminescence-based technology with tandem ubiquitin-binding entities (TUBE) to resolve substrate ubiquitination. To demonstrate the effectiveness and utility of this assay, we studied the compound-induced ubiquitination of G To S Phase Transition 1 (GSPT1) protein. Using this new assay, we characterized compounds with varying levels of GSPT1 ubiquitination activity. This method provides a novel cell based approach for assaying substrate ubiquitination in living cells that can be adapted to study the kinetics of ubiquitin transfer onto a substrate protein of interest. In addition, our results show that this approach is portable for studying ubiquitination of target proteins with varying functions

Nucleophilic addition reactions of bridged triene η6-chromiumtricarbonyl complexes

Bridged triene η6-chromiumtricarbonyl complexes have been shown to undergo regioselective addition reactions with a range of nucleophiles including organolithium reagents and enolates