Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens.

Enantioenriched Al-, Mg-, and Zn-enolates undergo electrophilic trapping by nitroolefins and vinylsulfones to afford 1,4-diketones and 2-(bis(phenylsulfonyl)ethyl)ketones in good yield and excellent diastereoselectivity. A one-pot preparation of indenes and enantiopure syntheses of tetrahydrobenzofurans, tetrahydrobenzopyrroles, and azulenes are disclosed. A site-selective two-step sequence of three conjugate additions is also demonstrated.

The natural phenomenon of drug resistance represents a generic impairment that hampers the benefits of drugs in all major clinical indications. Antibacterials and antifungals are affected as well as compounds for the treatment of cancer, viral infections or parasitic diseases. Despite the very diverse set of biological targets and organisms involved in the development of drug resistance, underlying molecular processes have been identified to understand the emergence of resistance and to overcome this detrimental mechanism. Detailed structural information of the root causes for drug resistance is nowadays frequently available to design next generation drugs anticipated to suffer less from resistance. This knowledge-based approach is a prerequisite in the fight against the inevitable occurrence of drug resistance to secure the achievements of medicinal chemistry in the future.

Seek, and ye shall find: After years of focusing research on synthetic antibiotics out of fear that all the useful natural ones had already been found, a novel antibacterial compound has been discovered through conventional microbial extract screening. The broad-spectrum nucleoside-analogue inhibitor pseudouridimycin is selective for bacterial RNA polymerase and elicits very low resistance rates.

Neue Strategien zur Bekämpfung von Antibiotikaresistenzen zu finden, ist eine der größten globalen Herausforderungen für die Gesundheitssysteme. In den letzten Jahrzehnten gab es eine drastische Zunahme an humanpathogenen Bakterien, die resistent gegen Antibiotika sind. Immer mehr Infektionen, die durch resistente Mikroorganismen verursacht werden, lassen sich nicht mehr mit konventionellen Behandlungen kurieren, und selbst Reserveantibiotika verlieren ihre Wirkung. Zusätzlich sind die Entwicklungsströme an neuen Antibiotika aus der pharmazeutischen Industrie in den letzten Jahrzehnten versiegt. Die Weltgesundheitsorganisation hat mit ihrem Aufruf “Combat drug resistance: no action today means no cure tomorrow” eine Zunahme der Forschungsaktivitäten auf diesem Gebiet stimuliert, und mehrere neue, vielversprechende Strategien zur Wiederherstellung antibiotischer Behandlungsoptionen konnten seitdem entwickelt werden.

The lithium diisopropylamide mediated halogen dance reaction of 5-iodooxazoles to generate 4-iodooxazoles was studied. The mechanism of the reaction was investigated and compared to the reported mechanism for the halogen dance rearrangement of 5-bromooxazoles. Reaction conditions were optimized and yields of iodooxazole were improved to a synthetically useful level. The use of 2-(butylsulfanyl)-5-bromooxazole as an organic catalyst turned out to be the cornerstone for the success of this reaction.

The synthesis of all key fragments of the marine macrolide leiodelide A is described. The polyoxygenated northern subunit is derived from d-xylose, while the southern subunit is rapidly assembled via an aldol reaction and Horner-Wadsworth-Emmons olefination. This highly convergent approach will allow for rapid modification and assembly of several isomers of leiodelide A, which may be necessary considering the assignment of leiodelide B has been previously shown to be incorrect.

Asymmetric organocatalytic annulation of E/Z isomeric mixtures of bis(alkyl carboxylate)buta-1,3-dienes and aldehydes has been realized via enamine catalysis. In the presence of R,R-diphenyl-2-pyrrolidinemethanol trimethylsilyl ether, excellent stereo-and enantioselectivities were achieved for a broad spectrum of substrates.The development of highly efficient asymmetric catalytic synthesis leading to enantiomerically enriched building blocks 1 represents one of the most important tasks of the modern organic chemist. In this research area, organocatalysis has emerged as one of the best approaches used in pursuit of this goal due to mild operative conditions, easy combination in cascade processes, and complementary reactivity to transition-metal catalysis.2 In particular, asymmetric conjugated addition of carbonyl compounds to electron-poor olefins has been broadly exploited to build high value chiral synthons with excellent stereo-and enantioselectivity. 3 In contrast, the application of activated dienes in asymmetric enamine catalysis is still poorly investigated. Over the last few of years, the application of electron-poor butadienes in inverse-electron-demand DielsÀAlder reactions via asymmetric enamine and dienamine catalysis has been reported. 4 Recently, our research group has described an exciting new reactivity involving a well-designed 1,3-bis(sulfonyl)butadiene in asymmetric 1,6-conjugated addition of aldehydes with excellent regio-and stereoselectivity followed by rapid in situ cyclization. 5 This new process gives access to interesting chiral polysubstituted cyclohexa-1,3-diene intermediates. † Department of Organic Chemistry, University of Geneva. (3) General reviews on asymmetric aminocatalysis: (a) Melchiorre, P.; Marigo, M.; Carlone, A.; Bartoli, G.