Copper(II)-Catalyzed Silyl Conjugate Addition to α,β-Unsaturated Conjugated Compounds: Brønsted Base-Assisted Activation of Si–B Bond in Water

A mild method for the installation of the dimethylphenylsilyl group on the β-carbon of electron-deficient olefins is reported. In the presence of a catalytic amount of copper(II) (1 mol %) and amine base (5 mol %) at rt, the transformation proceeds efficiently in water within 1.5–5 h to afford β-silylated products in yields of up to 90%

Unexpected Copper(II) Catalysis: Catalytic Amine Base Promoted β-Borylation of α,β-Unsaturated Carbonyl Compounds in Water

Using bis(pinacolato)diboron, catalytic amounts of Cu^II, and various amine bases in water under atmospheric conditions at rt, acyclic and cyclic α,β-unsaturated ketones and esters are β-borylated in up to 98% yield. Mechanistic investigations using UV–vis spectroscopy, ¹¹B NMR, and solvent kinetic isotope effect suggest that the role of the amine is not only to coordinate to Cu^II but also to activate a nucleophilic water molecule to form the reactive sp²–sp³ diboron complex

Regio- and Chemoselective Diboration of Allenes with Unsymmetrical Diboron: Formation of Vinyl and Allyl Boronic Acid Derivatives

A platinum-catalyzed terminal diboration of 1,1-disubstituted allenes using a differentially protected diboron is described. Diboration occurs in a regio- and chemoselective fashion to furnish vinyl and allyl boronates in good to excellent yield and selectivity. Transformation of the bis-boronyl products to other functional groups as well as in chemoselective cross-coupling is demonstrated

Chemo‑, Regio‑, and Stereoselective Copper(II)-Catalyzed Boron Addition to Acetylenic Esters and Amides in Aqueous Media

Aqueous conditions were developed for conducting an open-to-air, copper­(II)-catalyzed addition of pinBBdan to alkynoates and alkynamides. The simple and mild β-borylation protocol proceeds in a remarkably chemo-, regio-, and stereoselective fashion to afford 1,8-diamino­naphthalene protected (<i>Z</i>)-β-boryl enoates and primary, secondary, and tertiary enamides in good to excellent yields. These reactions demonstrate a high tolerance toward a variety of alkyl, aryl, and heteroatom functional groups and provide convenient access to a diverse range of vinylboronic acid derivatives

Light-Directed Patchy Particle Fabrication and Assembly from Isotropic Silver Nanoparticles

We demonstrate the creation of anisotropic patchy silver nanospheroids (AgNSs) using linearly polarized UV light and a photo-uncaging <i>o</i>-nitrobenzyl-based ligand, which anchors to the AgNSs by two gold-sulfur bonds. Exposure to a 1 J/cm² dose of UV light induces a photo-uncaging reaction in the ligand that reveals a primary amine on the surface. By using linearly polarized UV light, we meter the exposure dose such that only the poles of the nanoparticle receive a full dose, limiting the photo-uncaging reaction primarily to the particle’s plasmonic hot spots. We reveal this anisotropy by preferentially adhering negatively charged gold nanospheres (AuNSs) to the AgNSs’ poles by using the electrostatic attraction between them and the positively charged primary amines generated by photo-uncaging. When the assembly is performed onto silver particles that are immobilized on a substrate, it results in nanoscale structures with a strong tendency to align with the polarization of the exposing light. This manifests in polarimetric spectroscopy as a linear dichroism aligned with the polarization direction

Branched Peptides: Acridine and Boronic Acid Derivatives as Antimicrobial Agents

The emergence of microbial resistance presents a challenge in the development of next generation therapeutics. Herein, we report the discovery of branched peptides decorated with acridine and boronic acid moieties with potent antimicrobial activity. The results revealed minimal inhibitory concentrations (MICs) as low as 1 μg/mL against <i>Staphylococcus aureus</i>, <i>Candida albicans</i>, and <i>Escherichia coli</i>. These peptides were nonhemolytic, and significantly inhibited growth of <i>C. albicans</i> in suspension and biofilm formation. Structure–activity relationship studies suggest the acridine functional group as a driving force for the potent inhibition observed against bacteria

Transition Metal-Free <i>Trans</i> Hydroboration of Alkynoic Acid Derivatives: Experimental and Theoretical Studies

We report a phosphine-catalyzed <i>trans</i> hydroboration of alkynoate esters and amides. The reaction proceeds under mild conditions with exclusive (<i>E</i>)-selectivity to afford (<i>E</i>)-β-boryl acrylates and (<i>E</i>)-β-boryl acrylamides in good to excellent yields. The reaction is tolerant of a variety of functional groups and allows efficient access to novel oxaboroles as well as a pargyline derivative (MAO inhibitor). Theoretical calculations suggest an internal hydride generates a phosphonium allenoxyborane followed by the formation of a key phosphonocyclobutene intermediate that collapses in a stereoselective, rate-limiting step

Regio- and Stereoselective Copper(II)-Catalyzed Hydrosilylation of Activated Allenes in Water: Access to Vinylsilanes

By using catalytic amounts of copper­(II), 4-picoline, and dimethyl­phenylsilyl­pinacol borane, a series of allenoates were silylated on the β carbon in good to excellent yields and high (<i>E</i>)-selectivity. The mild and efficient silylation method is conducted in water under atmospheric conditions to afford vinylsilanes

Toward Targeting RNA Structure: Branched Peptides as Cell-Permeable Ligands to TAR RNA

Rational design of RNA ligands continues to be a formidable challenge, but the potential powerful applications in biology and medicine catapults it to the forefront of chemical research. Indeed, small molecule and macromolecular intervention are attractive approaches, but selectivity and cell permeability can be a hurdle. An alternative strategy is to use molecules of intermediate molecular weight that possess large enough surface area to maximize interaction with the RNA structure but are small enough to be cell-permeable. Herein, we report the discovery of nontoxic and cell-permeable branched peptide (BP) ligands that bind to TAR RNA in the low micromolar range from on-bead high-throughput screening of 4,096 compounds. TAR is a short RNA motif in the 5′-UTR of HIV-1 that is responsible for efficient generation of full RNA transcripts. We demonstrate that BPs are selective for the native TAR RNA structure and that “branching” in peptides provides multivalent interaction, which increases binding affinity to RNA

Transforming Sphingosine Kinase 1 Inhibitors into Dual and Sphingosine Kinase 2 Selective Inhibitors: Design, Synthesis, and in Vivo Activity

Sphingosine 1-phosphate (S1P) is a pleiotropic signaling molecule that interacts with its five G-protein coupled receptors (S1P_1–5) to regulate cell growth and survival and has been implicated in a variety of diseases including cancer and sickle cell disease. As the key mediators in the synthesis of S1P, sphingosine kinase (SphK) isoforms 1 and 2 have attracted attention as viable targets for pharmaceutical inhibition. In this article, we describe the design, synthesis, and biological evaluation of aminothiazole-based guanidine inhibitors of SphK. Surprisingly, combining features of reported SphK1 inhibitors generated SphK1/2 dual inhibitor <b>20l</b> (SLC4011540) (hSphK1 <i>K</i>_i = 120 nM, hSphK2 <i>K</i>_i = 90 nM) and SphK2 inhibitor <b>20dd</b> (SLC4101431) (<i>K</i>_i = 90 nM, 100-fold SphK2 selectivity). These compounds effectively decrease S1P levels in vitro. In vivo administration of <b>20dd</b> validated that inhibition of SphK2 increases blood S1P levels