Expedient and divergent synthesis of unnatural peptides through cobalt-catalyzed diastereoselective umpolung hydrogenation.

The development of a reliable method for asymmetric synthesis of unnatural peptides is highly desirable and particularly challenging. In this study, we present a versatile and efficient approach that uses cobalt-catalyzed diastereoselective umpolung hydrogenation to access noncanonical aryl alanine peptides. This protocol demonstrates good tolerance toward various functional groups, amino acid sequences, and peptide lengths. Moreover, the versatility of this reaction is illustrated by its successful application in the late-stage functionalization and formal synthesis of various representative chiral natural products and pharmaceutical scaffolds. This strategy eliminates the need for synthesizing chiral noncanonical aryl alanines before peptide formation, and the hydrogenation reaction does not result in racemization or epimerization. The underlying mechanism was extensively explored through deuterium labeling, control experiments, HRMS identification, and UV-Vis spectroscopy, which supported a reasonable CoI/CoIII catalytic cycle. Notably, acetic acid and methanol serve as safe and cost-effective hydrogen sources, while indium powder acts as the terminal electron source.

Cobalt-Catalyzed Asymmetric Deuteration of α-Amidoacrylates for Stereoselective Synthesis of α,ß-Dideuterated α-Amino Acids.

A cobalt-catalyzed deuteration of amidoacrylates using deuterated methanol afforded α,ß-dideuterio-α-amino esters in excellent enantiomeric ratios (mostly >95 : 5) and almost complete deuteration (99 %). The new protocol was used to prepare dideuterio-α-amino acid fragments in some drugs. Furthermore, the stereoselective deuteration was applied in a concise synthesis of dideuterio l-DOPA.

Asymmetric Hydroarylation of Enones via Nickel-Catalyzed 5-Endo-Trig Cyclization.

A nickel-catalyzed reductive cyclization of enones affords a wide array of indanones in high enantiomeric induction. The reaction is featured with an unprecedented broad scope of substrates. The versatility of the new method is demonstrated in several short stereoselective syntheses of medically valuable (R)-tolterodine, parent and deuterated (+)-indatraline, and an antitumor natural product, (+)-multisianthol. In comparison, these compounds cannot be prepared satisfactorily via analogous processes catalyzed by palladium.

Copper-Catalyzed Asymmetric Arylation of N-Heteroaryl Aldimines: Elementary Step of a 1,4-Insertion.

Copper complexes of monodentate phosphoramidites efficiently promote asymmetric arylation of N-azaaryl aldimines with arylboroxines. DFT calculations and experiments support an elementary step of 1,4-insertion in the reaction pathway, a step in which an aryl-copper species adds directly across four atoms of C=N-C=N in the N-azaaryl aldimines.

Recent Advances in the Catalytic Asymmetric Reactions of Oxaziridines.

Oxaziridines have emerged as powerful and elegant oxygen- and nitrogen-transfer agents for a broad array of nucleophiles, due to the remarkably high and tunable reactivities. However, the asymmetric catalysis involving oxaziridines is still in its infancy. Herein, this review aims to examine recent advances in the catalytic asymmetric transformations of oxaziridines, including oxidation, amination, cycloaddition and deracemization.

Nickel-Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Afford Indolines.

A nickel-catalyzed asymmetric reductive Heck reaction of aryl chlorides has been developed that affords substituted indolines with high enantioselectivity. Manganese powder is used as the terminal reductant with water as a proton source. Mechanistically, it is distinct from the palladium-catalyzed process in that the nickel-carbon bond is converted into a C-H bond to release the product through protonation instead of hydride donation followed by C-H reductive elimination on Pd.

Rhodium(III)-Catalyzed ortho C-H Heteroarylation of (Hetero)aromatic Carboxylic Acids: A Rapid and Concise Access to π-Conjugated Poly-heterocycles.

Rh(III)-catalyzed oxidative C-H/C-H cross-coupling between (hetero)aromatic carboxylic acids and various heteroarenes has been accomplished to construct highly functionalized ortho-carboxy-substituted bi(hetero)aryls. The use of a carboxy group as the directing group obviates tedious steps for installation and removal of extra directing groups, and enables a facile one-step synthesis of ortho-carboxy bi(hetero)aryls. The method provides opportunities for rapid assembly of a library of important fluorene and coumarin-type poly-heterocycles through intramolecular electrophilic substitution or oxidative lactonization. As illustrative examples, the strategy developed herein greatly streamlines accesses to a variety of appealing polyheterocycles such as DTPO (5H-dithieno[3,2-b:2',3'-d]pyran-5-one), CPDTO (cyclopentadithiophen-4-one), and indenothiophenes.

Rh(III)-catalyzed decarboxylative ortho-heteroarylation of aromatic carboxylic acids by using the carboxylic acid as a traceless directing group.

Highly selective decarboxylative ortho-heteroarylation of aromatic carboxylic acids with various heteroarenes has been developed through Rh(III)-catalyzed two-fold C-H activation, which exhibits a wide substrate scope of both aromatic carboxylic acids and heteroarenes. The use of naturally occurring carboxylic acid as the directing group avoids troublesome extra steps for installation and removal of an external directing group.

Rh(III)-catalyzed oxime ether-directed heteroarylation of arene through oxidative C-H/C-H cross-coupling.

A rhodium(III)-catalyzed dehydrogenative cross-coupling reaction has been developed for the synthesis of bi(hetero)aryl structures by using oxime ethers as the directing group. This protocol features a relatively broad substrate scope and a good tolerance of functional groups.

Cu-catalysed oxidative C-H/C-H coupling polymerisation of benzodiimidazoles: an efficient approach to regioregular polybenzodiimidazoles for blue-emitting materials.

The Cu-catalysed oxidative C-H/C-H coupling reaction of azoles has been used for the first time to develop polymerisation, which provides an efficient method for the preparation of polybenzodiimidazoles. These polymers exhibit high molecular weights, regioregularity, blue-emitting performance and thermal stability.

Regiospecific N-heteroarylation of amidines for full-color-tunable boron difluoride dyes with mechanochromic luminescence.

Colors to dye for: Palladium-catalyzed regiospecific N-heteroarylations of amidines with 2-halo-N-heteroarenes leads to a structurally diverse library of BF2 /amidine-based complexes. These dyes not only present full-visible-color solid-state emissions with large Stokes shifts and high fluorescence quantum yields, but also exhibit a full-color-tunable mechanofluorochromic nature.

Direct arylation of phenanthroline derivatives via oxidative C-H/C-H cross-coupling: synthesis and discovery of excellent ligands.

A concise synthetic protocol for aryl functionalized phenanthrolines has been developed. It was demonstrated that 3,8-diphenyl-1,10-phenanthroline (7a) is competent in promoting transition-metal-free direct arylation and 2,3,8,9-tetraphenyl-1,10-phenanthroline (8a) is a highly efficient ligand in the in situ Pd-catalysed Heck reaction.

Copper(II)-catalyzed dehydrogenative cross-coupling between two azoles.

The copper(II)-catalyzed dehydrogenative coupling between two different azoles for the preparation of unsymmetrical biazoles has been developed. The current catalytic system can effectively control the chemoselectivity for heterocoupling over homocoupling.

Palladium(II)-catalyzed oxidative C-H/C-H cross-coupling between two structurally similar azoles.

Power of two: A widely functional-group tolerant, selective and rapid oxidative cross-coupling between two structurally similar azoles has been carried out by using a palladium/copper co-catalytic twofold C-H activation method (see scheme).

Regiospecific synthesis of 1,2-disubstituted (hetero)aryl fused imidazoles with tunable fluorescent emission.

A palladium-catalyzed two or fourfold amination was established that allows regiospecific synthesis of a diversity-oriented library of 1,2-disubstituted (hetero)aryl fused imidazoles, and provides an exceptional tool for the discovery of fluorescent scaffolds with tunable fluorescence emission. These fluorophores have been applied as fluorescent probes for live cell imaging.

Synthesis of di(hetero)aryl sulfides by directly using arylsulfonyl chlorides as a sulfur source.

A new, efficient protocol for the synthesis of di(hetero)aryl sulfides is described. Cheap and easily available arylsulfonyl chlorides as a sulfur source reductively couple with electron-rich (hetero)arenes (e.g., indolizines, indoles, electron-rich benzenes, etc.) in the presence of triphenylphosphine to afford di(hetero)aryl thioethers in good yields.

One-pot synthesis of benzofused heteroaryl azoles via tandem C-heteroatom coupling/C-H activation of azoles.

The Cu(I) or Pd(II)-catalyzed cross-couplings of gem-dihaloolefins with azoles via tandem C-heteroatom coupling/C-H activation for the preparation of benzofused heteroaryl azoles have been developed.

Hemolysis of human erythrocytes induced by melamine-cyanurate complex.

Melamine is a widely-used chemical in industries. In recent years, melamine has been found to be involved in outbreaks of renal injury in infants and animals. Pathological studies indicated that the melamine-induced acute renal failure was related to the concurrence of melamine and other triazine analogs such as cyanuric acid. In the present study, human erythrocytes were used as an in vitro model to explore the cytotoxicity of melamine and its complex with cyanuric acid. The results demonstrated that mixing melamine and cyanuric acid resulted in the formation of insoluble particles and that the insoluble melamine-cyanurate complex induced membrane damages of human erythrocytes. The membrane damages included hemolysis, K(+) leakage, alterations in cell shape and membrane fragility, and inhibition of enzymatic activity. By contrast, either melamine or cyanuric acid alone had no effect on erythrocyte membranes. The results of this study may provide a fresh insight into the melamine toxicology.

A B-box 2 surface patch important for TRIM5alpha self-association, capsid binding avidity, and retrovirus restriction.

TRIM5alpha is a tripartite motif (TRIM) protein that consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The TRIM5alpha(rh) protein from rhesus monkeys recognizes the human immunodeficiency virus type 1 (HIV-1) capsid as it enters the host cell and blocks virus infection prior to reverse transcription. HIV-1-restricting ability can be eliminated by disruption of the B-box 2 domain. Changes in the TRIM5alpha(rh) B-box 2 domain have been associated with alterations in TRIM5alpha(rh) turnover, the formation of cytoplasmic bodies and higher-order oligomerization. We present here the nuclear magnetic resonance structure of the TRIM5 B-box 2 domain and identify an unusual hydrophobic patch (cluster 1) on the domain surface. Alteration of cluster 1 or the flanking arginine 121 resulted in various degrees of inactivation of HIV-1 restriction, in some cases depending on compensatory changes in other nearby charged residues. For this panel of TRIM5alpha(rh) B-box 2 mutants, inhibition of HIV-1 infection was strongly correlated with higher-order self-association and binding affinity for capsid complexes but not with TRIM5alpha(rh) half-life or the formation of cytoplasmic bodies. Thus, promoting cooperative TRIM5alpha(rh) interactions with the HIV-1 capsid represents a major mechanism whereby the B-box 2 domain potentiates HIV-1 restriction.