New antimicrobial self-assembling short lipopeptides.

Lipopeptides are an exceptional example of amphiphilic molecules that self-assemble into functional structures with applications in the areas of nanotechnology, catalysis or medicinal chemistry. Herein, we report a library of 21 short lipopeptides, together with their supramolecular characterization and antimicrobial activity against both Gram-negative (E. coli) and Gram-positive (S. aureus) strains. This study shows that simple lipoamino acids self-assemble into micellar or vesicular structures, while incorporating dipeptides capable of stablishing hydrogen bonds results in the adoption of advanced fibrilar structures. The self-assembly effect has proven to be key to achieve antimicrobial activity.

Sulfinyl-Mediated Stereoselective Functionalization of Acyclic Conjugated Dienes.

The chemo- and stereocontrolled functionalization of conjugated sulfinyl dienes in a cascade process that involves a conjugate addition, diastereoselective protonation and a [2,3]-sigmatropic rearrangement is reported. Enantioenriched 1,4-diol and 1,4-aminoalcohol derivatives are obtained in a very straightforward manner. Further functionalization of these structures, including highly stereoselective epoxidation, dihydroxylation and the stereodivergent synthesis of several polyols in a controlled fashion is described.

HFIP Solvent Enables Alcohols To Act as Alkylating Agents in Stereoselective Heterocyclization.

A new method for the stereoselective synthesis of highly functionalized oxygen heterocycles using allyl or benzyl alcohols as alkylating agents is presented. The process is efficient and atom economic, generating water as the only stoichiometric byproduct. Substoichiometric amounts of Ti(OiPr)4 in HFIP solvent are key to this reactivity, and the method tolerates a broad substitution pattern on both the alcohol initiator and homoallylic alcohol substrate. Preliminary mechanistic studies reveal in situ formation of a titanium complex with HFIP which may initiate the cyclization reaction. Further stereoselective functionalization of the products allows access to a diverse range of interesting heterocyclic structures.

From Allylic Sulfoxides to Allylic Sulfenates: Fifty Years of a Never-Ending [2,3]-Sigmatropic Rearrangement.

The [2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenates is a reversible process, generally shifted toward the sulfoxide. In the presence of thiophiles, the sulfenate is trapped, and allylic alcohols are obtained under mild conditions. In most cases, a good transfer of stereochemical information through an ordered transition state is obtained. Furthermore, the ease of coupling this process with other versatile, stereocontrolled reactions has enhanced the usefulness of this protocol. This review aims to provide a comprehensive survey of this rearrangement and its application in the synthesis of natural and bioactive products.

Hydrogen Bonding to Hexafluoroisopropanol Controls the Oxidative Strength of Hypervalent Iodine Reagents.

Hexafluoroisopropan-2-ol (HFIP) has been found to be an unusually beneficial solvent for undertaking hypervalent iodine-initiated [2+2] cycloaddition of styrenes. For the initiator phenyliodine(III) diacetate (PIDA), voltammetric data demonstrate that the enhanced reactivity in HFIP is due to its greater oxidizing abilities in this fluorinated solvent such that in HFIP the reactivity of PIDA is comparable if not superior to its fluorinated analog phenyliodine(III) bis(trifluoroacetate). These results contrast with the often reported view that the role of the fluoroalcohol is to stabilize a radical cation formed by single electron transfer. Moreover, combined NMR and HRMS results reveal the formation of a strong H-bonded adduct between the solvent and oxidizing reagent which is the physical origin of the observed altered synthetic reactivity.

Sulfinyl-Mediated Stereoselective Overman Rearrangements and Diels-Alder Cycloadditions.

Sulfinyl trichloroacetamides are readily obtained in excellent yields through a highly stereoselective Overman rearrangement. Related bis-allylic substrates lead to amido 2-sulfinyl butadiene derivatives in excellent yields, with total chemo- and diastereoselectivity. These amido dienyl sulfoxides undergo highly selective Diels-Alder cycloadditions with N-phenylmaleimide with remarkable stereocontrol by the sulfoxide moiety.

Catalytic Hypervalent Iodine Promoters Lead to Styrene Dimerization and the Formation of Tri- and Tetrasubstituted Cyclobutanes.

Reported herein is that the use of catalytic quantities of hypervalent iodine reagents (phenyliodine diacetate or Dess-Martin periodinane) allows the rapid and stereoselective formation of cyclobutanes under very mild reaction conditions. The presence of a fluorinated solvent is essential for the success of these reactions which form unsymmetrical tri- and tetrasubstituted cyclobutanes through a heterodimerization process involving two different alkenes.

Aminomethylhydroxylation of alkenes: Exploitation in the synthesis of scaffolds for small molecule libraries.

The application of [4+2] cycloadditions between alkenes and an N-benzoyl iminium species, generated in situ under acidic conditions, is described in the synthesis of diverse molecular scaffolds. The key reaction led to the formation of cyclic imidates in good yield and with high regioselectivity. It was demonstrated that the cyclic imidates may be readily converted into 1,3-amino alcohols. Incorporation of orthogonally-reactive functionality, such as aryl and alkyl bromides, into the cycloaddition substrates enabled the synthesis of additional scaffolds. For one scaffold, the synthesis of exemplar screening compounds was undertaken to demonstrate potential value in small molecule library production.

Understanding the Regiodivergence between Hydroarylation and Trifluoromethylarylation of 1,3-Dienes Using Anilines in HFIP.

Conjugated dienes (1,3-dienes) are versatile and valuable chemical feedstocks that can be used as two-carbon or four-carbon synthons with vast applications across the chemical industry. However, the main challenge for their productive incorporation in synthetic routes is their chemo-, regio-, and stereoselective functionalization. Herein, we introduce a unified strategy for the 1,2-hydroarylation and 1,4-trifluoromethylarylation of 1,3-dienes using anilines in hexafluoroisopropanol. DFT calculations point toward a kinetically controlled process in both transformations, particularly in the trifluoromethylarylation, to explain the regiodivergent outcome. In addition, we perform an extensive program of functionalization and diversification of the products obtained, including hydrogenation, oxidation, cyclizations, or cross-coupling reactions, that allows access to a library of high-value species in a straightforward manner.

Trifluoromethylarylation of alkenes using anilines.

Nitrogen containing compounds, such as anilines, are some of the most widespread and useful chemical species, although their high and unselective reactivity has prevented their incorporation into many interesting transformations, such as the functionalization of alkenes. Herein we report a method that allows the trifluoromethylarylation of alkenes using anilines, for the first time, with no need for additives, transition metals, photocatalysts or an excess of reagents. An in-depth mechanistic study reveals the key role of hexafluoroisopropanol (HFIP) as a unique solvent, establishing a hydrogen bonding network with aniline and trifluoromethyl reagent, that is responsible for the altered reactivity and exquisite selectivity. This work uncovers a new mode of reactivity that involves the use of abundant anilines as a non-prefunctionalized aromatic source and the simultaneous activation of trifluoromethyl hypervalent iodine reagent.

Lipopeptides as tools in catalysis, supramolecular, materials and medicinal chemistry.

Lipopeptides are amphiphilic peptides in which an aliphatic chain is attached to either the C or N terminus of peptides. Their self-assembly - into micelles, vesicles, nanotubes, fibres or nanobelts - leads to applications in nanotechnology, catalysis or medicinal chemistry. Self-organization of lipopeptides is dependent on both the length of the lipid tail and the amino acid sequence, in which the chirality of the peptide sequence can be transmitted into the supramolecular species. This Review describes the use of lipopeptides to design synthetic advanced dynamic supramolecular systems, nanostructured materials or self-responsive delivery systems in the area of medical biotechnology. We examine the influence of external stimuli, the ability of lipopeptide-derived structures to adapt over time and their application as medicinal agents with antibacterial, antifungal, antiviral or anticancer activities. Finally, we discuss the catalytic efficiency of lipopeptides, with the aim of building minimal synthetic enzymes, and recent efforts to incorporate metals into lipopeptide assemblies.

Enantioselective cyclizations of silyloxyenynes catalyzed by cationic metal phosphine complexes.

The discovery of complementary methods for enantioselective transition metal-catalyzed cyclization with silyloxyenynes has been accomplished using chiral phosphine ligands. Under palladium catalysis, 1,6-silyloxyenynes bearing a terminal alkyne led to the desired five-membered ring with high enantioselectivities (up to 91% ee). As for reactions under cationic gold catalysis, 1,6- and 1,5-silyloxyenynes bearing an internal alkyne furnished the chiral cyclopentane derivatives with excellent enantiomeric excess (up to 94% ee). Modification of the substrate by incorporating an α,ß-unsaturation led to the discovery of a tandem cyclization. Remarkably, using silyloxy-1,3-dien-7-ynes under gold catalysis conditions provided the bicyclic derivatives with excellent diastereo- and enantioselectivities (up to >20:1 dr and 99% ee).

An approach to the stereoselective synthesis of enantiopure dihydropyrroles and aziridines from a common sulfinyl-sulfinamide intermediate.

The diastereoselective addition of lithiated vinyl sulfoxides to enantiopure sulfinimines provides direct access to a wide assortment of allylic sulfinamides in good yields and excellent selectivities. These adducts are key precursors to differently functionalized cis- and trans-dihydropyrroles. Modulation of the protecting group on nitrogen prior to cyclization has a significant impact on the stereochemical outcome, allowing for the selective preparation of 2,5-cis- or 2,5-trans-3-sulfinyl disubstituted dihydropyrroles from a common sulfinamide intermediate. Further research on halocyclization conditions has also yielded a stereoselective synthesis of trisubstituted vinyl aziridines from these chiral sulfinamides, simply by changing the halogenating agent.

Selection from a pool of self-assembling lipid replicators.

Replication and compartmentalization are fundamental to living systems and may have played important roles in life's origins. Selection in compartmentalized autocatalytic systems might provide a way for evolution to occur and for life to arise from non-living systems. Herein we report selection in a system of self-reproducing lipids where a predominant species can emerge from a pool of competitors. The lipid replicators are metastable and their out-of-equilibrium population can be sustained by feeding the system with starting materials. Phase separation is crucial for selective surfactant formation as well as autocatalytic kinetics; indeed, no selection is observed when all reacting species are dissolved in the same phase. Selectivity is attributed to a kinetically controlled process where the rate of monomer formation determines which replicator building blocks are the fittest. This work reveals how kinetics of a phase-separated autocatalytic reaction may be used to control the population of out-of-equilibrium replicators in time.

Compatibility of early natural enemy introductions in commercial pepper and tomato greenhouses with repeated pesticide applications.

Successful integrated pest management in protected crops implies an evaluation of the compatibility of pesticides and natural enemies (NE), as control strategies that only rely on one tactic can fail when pest populations exceed NE activity or pests become resistant to pesticides. Nowadays in Almería (Spain), growers release NE prior to transplanting or early in the crop cycle to favor their settlement before pest arrival because this improves biocontrol efficacy, although it extends pesticide exposure periods. The purpose of this research was to evaluate the compatibility of two applications of pesticides with key NE in 2-year trials inside tomato and sweet pepper commercial greenhouses: Nesidiocoris tenuis (Reuter) (Hemiptera: Miridae), Orius laevigatus (Say) (Hemiptera: Anthocoridae) and Amblyseius swirskii (Athias-Henriot) (Acari: Phytoseiidae). In tomato, flubendiamide and chlorantraniliprole (IOBC category 1) were compatible with N. tenuis, but chlorpyrifos-methyl and spinosad (IOBC categories 2-3), which effectively reduced Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) density, compromised its predatory activity. In sweet pepper, chlorantraniliprole (IOBC category 1) was the only pesticide compatible with O. laevigatus while chlorantraniliprole, emamectin benzoate, spirotetramat and pymetrozine were harmless (IOBC category 1) to Amblyseius swirskii, and sulfoxaflor slightly harmful (IOBC category 2) to this phytoseiid predator.

Highly diastereoselective Katsuki-Jacobsen oxidation-epoxidation of alpha-silyloxy sulfinyl dienes: synthetic applications.

Katsuki-Jacobsen oxidation-epoxidation of acyclic alpha-silyloxy sulfinyl dienes, followed by acid-promoted cyclization, leads to 2,5-trans-sulfonyl dihydrofurans with good selectivities. As an application, the formal syntheses of (6S,7S,9R,10R)- and (6S,7S,9S,10S)-6,9-epoxynonadec-18-ene-7,10-diols is reported.

Hypervalent iodine initiated intramolecular alkene dimerisation: a stereodivergent entry to cyclobutanes.

The emergence of new methods for the stereoselective synthesis of strained carbocycles is a challenging but worthwhile endeavour. Cyclobutanes, in particular, have attracted the attention of both medicinal chemists and material scientists for their unique properties. Herein, we present a new method that allows access to highly functionalized cyclobutanes with complementary all-trans and trans-cis-trans relative stereochemistry, that could not be accessed before. This approach consists of an intramolecular dimerisation of non-conjugated dienes using an oxidative single electron transfer (SET) process, and is initiated by catalytic amounts of hypervalent iodine reagents. The potential uses of these cyclobutanes is demonstrated with selective functionalization, including the formation of diols and carboxylic acids.

A chemically fuelled self-replicator.

The continuous consumption of chemical energy powers biological systems so that they can operate functional supramolecular structures. A goal of modern science is to understand how simple chemical mixtures may transition from non-living components to truly emergent systems and the production of new lifelike materials and machines. In this work a replicator can be maintained out-of-equilibrium by the continuous consumption of chemical energy. The system is driven by the autocatalytic formation of a metastable surfactant whose breakdown products are converted back into building blocks by a chemical fuel. The consumption of fuel allows the high-energy replicators to persist at a steady state, much like a simple metabolic cycle. Thermodynamically-driven reactions effect a unidirectional substrate flux as the system tries to regain equilibrium. The metastable replicator persists at a higher concentration than achieved even transiently in a closed system, and its concentration is responsive to the rate of fuel supply.

A transient self-assembling self-replicator.

Developing physical models of complex dynamic systems showing emergent behaviour is key to informing on persistence and replication in biology, how living matter emerges from chemistry, and how to design systems with new properties. Herein we report a fully synthetic small molecule system in which a surfactant replicator is formed from two phase-separated reactants using an alkene metathesis catalyst. The replicator self-assembles into aggregates, which catalyse their own formation, and is thermodynamically unstable. Rather than replicating until the reactants are fully consumed, the metastable replicator is depleted in a second metathesis reaction, and closed system equilibrium is eventually reached. Mechanistic experiments suggest phase separation is responsible for both replicator formation and destruction.

Efficacy of a long-lasting bifenthrin-treated net against horticultural pests and its compatibility with the predatory mite Amblyseius swirskii and the parasitic wasp Eretmocerus mundus.

BACKGROUND: Insecticide-treated nets (ITNs) have been investigated recently for their use in agriculture. Depending on the insecticide, the hole size and the way they are produced, these nets can target different pests and therefore they could be interesting options for use in integrated pest management (IPM). As the information on their compatibility with beneficial fauna is practically negligible, in this work we have tested the compatibility of an experimental bifenthrin long-lasting insecticide-treated net (LLITN) with Amblyseius swirskii and Eretmocerus mundus, important natural enemies of whiteflies and thrips, under laboratory, semi-field and commercial greenhouse conditions. RESULTS: In the laboratory, the treated net was very deleterious to adults of both natural enemies, after 72 h exposure. However, in choice tests with Y-tubes, both natural enemies were neither attracted nor repelled by the treated net and no short-term mortality was detected in individuals that had crossed it. No deleterious effects on the E. mundus beneficial capacity were detected in semi-field trials. In field trials, the LLITN proved to be compatible with A. swirskii while decreasing pest densities. CONCLUSIONS: Bifenthrin LLITN studied could be a valuable method for reducing pest population infestations in IPM programmes while being compatible with biocontrol agents. © 2017 Society of Chemical Industry.