A noticeable increase in molecular complexity of drug targets has created an unmet need the therapeutic agents that are larger than traditional small molecules. Macrocycles, which cyclic compounds comprising 12 atoms or more, now recognized as molecules "are up to task" interrogate extended protein interfaces. However, because macrocycles (particularly ones based on peptides) equipped with large polar surface areas, achieving cellular permeability and bioavailability is anything but...

In recent years, our search for new nitrogen transfer reactions has concentrated on aziridine chemistry. This Account highlights efforts toward the synthesis and functionalization of aziridines. course research, we have investigated electrochemical aziridination olefins, acid-catalyzed ring opening aziridines, development transition metal mediated allylation, arylation, alkenylation unprotected Our studies also involved aziridine-based enamine intermediates their stereoselective...

Achieving high levels of chemoselectivity has been the Achilles' heel chemical synthesis. The excitement generated by successful realization chemoselective strategies underscores painstaking efforts to define a set conditions conducive selection among available reaction pathways. We discuss in this Review various aspects that have addressed range synthetic methods over past decade. focused on proposed mechanistic basis reactions under consideration an attempt categorize them and highlight...

There has been enormous interest in both naturally occurring and synthetic cyclic peptides as scaffolds that preorganize a given amino acid sequence into rigid conformation. Such molecules have employed nanomaterials, imaging agents, therapeutics. Unfortunately, the laboratory synthesis of directly from linear precursors is afflicted by several thermodynamic kinetic challenges, resulting low chemical yields poor chemo- stereoselectivities. Here we report amphoteric aldehydes can be used for...

A new class of stable molecules, α-boryl aldehydes, has been prepared from oxiranyl N-methyliminodiacetyl boronates by a 1,2-boryl migration with concomitant epoxide scission. range boryl imines, alkenes, alcohols, acids, enol ethers, enamides, and other functionalized boronic acid derivatives that are difficult or impossible to prepare using established protocols can be accessed aldehydes. The chemoselective transformations these building blocks, including the facile synthesis unnatural...

ConspectusResearchers continue to develop chemoselective synthesis strategies with the goal of rapidly assembling complex molecules. As one appealing approach, chemists are searching for new building blocks that include multiple functional groups orthogonal chemical reactivity. Amphoteric molecules possess nucleophilic and electrophilic sites offer a versatile platform development transformations. part program focused on methods synthesis, we have been developing this type reagents.This...

The present study illustrates the possibility of a rational approach that bypasses requirement for stoichiometric amounts toxic oxidants and metal additives (including reagents catalysts) in organic redox reactions. We describe an aziridination process delivers nitrene functionality to olefins from readily available N-aminophthalimide. Remarkably, both electron-rich electron-poor are converted aziridines with high efficiency. continuum applied potentials heterogeneous nature reactions at...

ADVERTISEMENT RETURN TO ISSUEPREVNoteNEXTA Simple and Efficient Method for the Preparation of Pyridine N-OxidesChristophe Copéret, Hans Adolfsson, Tinh-Alfredo V. Khuong, Andrei K. Yudin, Barry SharplessView Author Information Department Chemistry Skaggs Institute Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 Cite this: J. Org. Chem. 1998, 63, 5, 1740–1741Publication Date (Web):February 18, 1998Publication History Received31...

A comparative investigation into palladium-catalyzed allylic amination of unsubstituted aziridines and secondary amines has been carried out. The use NH as nucleophiles favors formation valuable branched products in the case aliphatic allyl acetates. regioselectivity this reaction is opposite to that observed when other are used nucleophiles. Our study provides evidence for isomerization (kinetic) product formed with common thermodynamic (linear) product. In contrast, obtained from do not...

Excellent tolerance: Stable acylboronates equipped with N-methyliminodiacetyl (MIDA) boryl groups ([B]) were prepared by using a sequence of oxidative manipulations at the boron-bound carbon center (green in scheme). Chemoselective transformations these acylated organoboron building blocks yielded range multifunctionalized boron derivatives and supplied access to valuable borylated heterocycles (see Organoboronic acids their are widely utilized chemical synthesis.1 The reactivity molecules...

Digital synthesis has been applied to the formation of peptide-based macrocycles and their analogues with side chains appended during late-stage aziridine ring-opening. Discrete nanoliter- microliter-sized droplets samples reagents are controlled in parallel by applying a series electrical potentials an array electrodes coated hydrophobic insulator.

A reaction exemplifying migration of boron-substituted carbon is described. We show that α-boroalkyl groups transient boroalkyl acyl azide intermediates readily migrate from to nitrogen. This process allows access a new class stable molecules, α-boryl isocyanates, α-borylcarboxylic acid precursors. The methodology facilitates synthesis wide range α-aminoboronic derivatives, including α,α-disubstituted analogues.

Herein, we describe the bromomethyl acyl boronate linchpin--an enabling reagent for condensation-driven assembly of novel bis(heteroaryl) motifs. This building block is readily accessible from commercially available starting materials. A variety 2-amino- and 2-methylpyridines were reacted with MIDA-protected acylboronate to afford 2-boryl imidazo[1,2-a]pyridine indolizine derivatives, respectively, in excellent yields. Subsequent condensation hydroxyamidines hydrazonamides converted...

Described herein is the preparation of oxalyl boronate building blocks and their application for construction heterocycles. The unit, readily accessible through commercially available starting materials, enables a modular approach synthesis imidazoles. A variety aromatic, heteroaromatic, alkyl carboxaldehydes were condensed with boronates to afford substituted boryl imidazoles in regiocontrolled fashion. Subsequent palladium-catalyzed cross-coupling haloarenes furnished desired...