Intramolecular,Interrupted Homo-Nazarov Cascade Biscyclizations to Angular (Hetero)Aryl-Fused Polycycles

Herein, a SnCl₄-catalyzed intramolecular, interrupted homo-Nazarov cascade biscyclization to access angular (hetero)aryl-fused polycycles is reported. Subsequent decarboxylation of the readily enolizable products afforded the angular products in up to 71 % yield over two steps, with the trans-diastereomers as the major products. The cyclopropyl homo-Nazarov cyclization precursors were formed using a scalable and modular synthetic route that, ultimately, offers access to 6,6,6-, 6,6,5-, 6,5,6-, 6,6,5,6-, and 6,6,6,5-fused angular polycyclic products. To showcase the rigor and utility of the method, an 8-step total synthesis of (±)-1-oxoferruginol, an antibacterial aromatic abietane diterpenoid, was disclosed.     

Active Intracellular Delivery of a Cas9/sgRNA Complex Using Ultrasound‐Propelled Nanomotors

Direct and rapid intracellular delivery of a functional Cas9/sgRNA complex using ultrasound‐powered nanomotors is reported. The Cas9/sgRNA complex is loaded onto the nanomotor surface through a reversible disulfide linkage. A 5 min ultrasound treatment enables the Cas9/sgRNA‐loaded nanomotors to directly penetrate through the plasma membrane of GFP‐expressing B16F10 cells. The Cas9/sgRNA is released inside the cells to achieve highly effective GFP gene knockout. The acoustic Cas9/sgRNA‐loaded nanomotors display more than 80 % GFP knockout within 2 h of cell incubation compared to 30 % knockout using static nanowires. More impressively, the nanomotors enable highly efficient knockout with just 0.6 nm of the Cas9/sgRNA complex. This nanomotor‐based intracellular delivery method thus offers an attractive route to overcome physiological barriers for intracellular delivery of functional proteins and RNAs, thus indicating considerable promise for highly efficient therapeutic applications.     

Epoxides related to dioncoquinone B: Synthesis,activity against multiple myeloma cells,and search for the target protein

Epoxide 2b is an analog of the synthetic intermediate 2a en route to the polyketide-derived antitumoral naphthoquinone dioncoquinone B (1), isolated from cell cultures of the tropical liana Triphyophyllum peltatum (Dioncophyllaceae). Compound 2b was found to induce strong apoptosis in multiple myeloma cells at a concentration (EC₅₀?=?3.5?μM), distinctly lower than that of 1 and any related analog, without exerting significant toxicity against normal blood cells. Preliminary studies showed that 2b follows different SAR rules as compared to the naphthoquinones. Among the series of synthesized epoxides, 2b was the most active one and was thus, after biotinylation, subjected to mass spectrometry-based affinity capture experiments aiming at the identification of target proteins. The MS data revealed 2b to address proteins that are associated with stress regulation processes which are critical for multiple myeloma cell survival.     

Targeting the bacterial Z-ring

FtsZ is a prokaryotic homolog of eukaryotic tubulin and forms the essential bacterial cell division ring (Z-ring). A new study in this issue of Chemistry & Biology, L?ppchen et al., provides further evidence that differences in nucleotide-binding properties of FtsZ and tubulin can be exploited to specifically target the bacterial Z-ring.     

Simultaneous Identification of Spectral Properties and Sizes of Multiple Particles in Solution with Subnanometer Resolution

We report an unsurpassed solution characterization technique based on analytical ultracentrifugation, which demonstrates exceptional potential for resolving particle sizes in solution with sub‐nm resolution. We achieve this improvement in resolution by simultaneously measuring UV/Vis spectra while hydrodynamically separating individual components in the mixture. By equipping an analytical ultracentrifuge with a novel multi‐wavelength detector, we are adding a new spectral discovery dimension to traditional hydrodynamic characterization, and amplify the information obtained by orders of magnitude. We demonstrate the power of this technique by characterizing unpurified CdTe nanoparticle samples, avoiding tedious and often impossible purification and fractionation of nanoparticles into apparently monodisperse fractions. With this approach, we have for the first time identified the pure spectral properties and band‐gap positions of discrete species present in the CdTe mixture.