Allyl Sulfides Research Articles

Syntheses of 4-allyl-/4-allenyl-4-(arylthio)-1,4-dihydroisoquinolin-3-ones via the photochemical Doyle–Kirmse reaction

Facile synthesis of 4-allyl-/4-allenyl-4-(arylthio)-1,4-dihydroisoquinolin-3-ones via the visible-light-induced Doyle-Kirmse reaction of 4-diazo-1,4-dihydroisoquinolin-3-ones with allyl-/propargyl sulfides is reported. The reaction proceeds via the generation of free carbenes from cyclic diazo compounds followed by in situ formation of sulfonium ylide intermediates, which subsequently undergo [2,3-sigmatropic rearrangement] to give highly functionalized dihydroisoquinolinones in moderate to good yields. Broad substrate scope, and catalyst-free and mild conditions are the merits of this reaction.

K2S2O8 promoted dehydrative cross-coupling between α,α-disubstituted allylic alcohols and thiophenols/thiols

K2S2O8 promoted dehydrative cross-coupling between α,α-disubstituted allylic alcohols and thiophenols/thiols is demonstrated for the first time, leading to a wide range of allyl sulfides in good to high yields.

Palladium catalyzed desulfurative coupling of allyl sulfides with organoboronic acids

A palladium catalyzed desulfurative coupling of allylthioethers with organoboronic acids under mild reaction conditions is described.

Catalytic Chemoselective Sulfimidation with an Electrophilic [CoIII (TAML)]- -Nitrene Radical Complex*.

The cobalt species PPh4[CoIII(TAMLred)] is a competent and stable catalyst for the sulfimidation of (aryl)(alkyl)‐substituted sulfides with iminoiodinanes, reaching turnover numbers up to 900 and turnover frequencies of 640 min−1 under mild and aerobic conditions. The sulfimidation proceeds in a highly chemoselective manner, even in the presence of alkenes or weak C−H bonds, as supported by inter‐ and intramolecular competition experiments. Functionalization of the sulfide substituent with various electron‐donating and electron‐withdrawing arenes and several alkyl, benzyl and vinyl fragments is tolerated, with up to quantitative product yields. Sulfimidation of phenyl allyl sulfide led to [2,3]‐sigmatropic rearrangement of the initially formed sulfimide species to afford the corresponding N‐allyl‐S‐phenyl‐thiohydroxylamines as attractive products. Mechanistic studies suggest that the actual nitrene transfer to the sulfide proceeds via (previously characterized) electrophilic nitrene radical intermediates that afford the sulfimide products via electronically asynchronous transition states, in which SET from the sulfide to the nitrene radical complex precedes N−S bond formation in a single concerted process.

Gold-Catalyzed Asymmetric Thioallylation of Propiolates via Charge-Induced Thio-Claisen Rearrangement.

A gold(I)-catalyzed enantioselective thioallylation of propiolates with allyl sulfides is described. The key mechanistic element is a sulfonium-induced Claisen rearrangement which helps minimize the allyl dissociation and render higher enantioselectivity. This protocol features remarkable scope of the allyl moiety, allowing enantiocontrolled synthesis of all-carbon quaternary centers, and exhibits exceptional functional group compatibility with many Lewis bases and π-bonds. This intermolecular variant of Claisen rearrangement forges both C-S and C-C bonds concomitantly, providing efficient access to interesting optically active organosulfur compounds which can be transformed further through the vinyl sulfide as a functional handle. The rate of the reaction was zeroth order with respect to allyl sulfides, which suggested a reversible inhibition, providing a resting state for the catalyst. The Hammett plot displayed a correlation with σp values, suggesting a turnover-limiting sigmatropic rearrangement where decreased electron-density on sulfur accelerated the rearrangement.

Diastereoselective sulfur ylide rearrangements from gold catalyzed oxidation of ynamides

The [2,3]-sigmatropic rearrangement of sulfonium ylides bearing substituted allyl groups creates two contiguous stereocentres. Low diastereoselectivity is typically observed from commonly used α-diazocarboxylic ester precursors. High diastereoselectivity was previously revealed in a gold-catalyzed multicomponent route into allyl sulfonium ylides by reaction of ynamide, oxidant and allyl sulfides. The effect of substrate modifications on the diastereoselectivity have been studied, with N -phenyl methanesulfonamide derived ynamides proving the most effective. This report includes an enhanced experimental procedure, and a demonstration that the gold-catalyzed process remains highly effective at −78 °C.

Imino‐λ3‐iodane and Catalytic Amount of I2‐Mediated Synthesis ofN‐Allylsulfenamides via [2,3]‐Sigmatropic Rearrangement

A facile metal‐free [2,3]‐sigmatropic rearrangement reaction of allyl sulfides viaN‐sulfilimine intermediates has been developed. Treatment of allyl sulfides with imino‐λ3‐iodanes in the presence of a catalytic amount of elemental iodine allowed the reaction to proceed under mild conditions and gave the correspondingN‐allylsulfenamide compounds in moderate to good yields. SeveralN‐allylsulfenamide structures have been confirmed by single‐crystal X‐ray crystallography. The reaction initially involves the sulfonylimino group transfer reaction between imino‐λ3‐iodane and the sulfur atom, resulting in the formation ofN‐sulfilimine species, followed by [2,3]‐sigmatropic rearrangement to form theN‐allylsulfenamide.

Chiral Cobalt(II) Complex Catalyzed Asymmetric [2,3]-Sigmatropic Rearrangement of Allylic Selenides with α-Diazo Pyrazoleamides

Organoselenium compounds, due to their high structural diversity, special function, and biological activities, have drawn attention in synthetic chemistry. Herein, a novel example of chiral N,N′-di...

Reactivity of allyl methyl sulphide, the in-vitro metabolite of garlic, with some amino acids and with phospholipid involved in viral infections

Garlic, as well as several natural food ingredients such as basil, ginger, turmeric, cinnamon, clove, pepper etc., has long been traditionally used as routine anti-viral and anti-bacterial remedy. Allyl methyl sulfide (AMS) is reportedly a persistent main active metabolite component of allicin after garlic ingestion accounting for at least 90% of the allicin consumed. Several studies have reported the presence of AMS in organs such as lung, kidney etc. and body fluids such as mucous, and blood-plasma. Glycoproteins of enveloped viruses are actively involved in viral pathogenesis. N-acetylneuraminic acid (sialic acid) and N-Acetylglucosamine, are some of the vital amino acids involved in several viral infections using glycoproteins via glycosylation. Simulations studies based on First-principles density functional theory show that these amino acids attach with AMS, and the reactions are thermodynamically spontaneous (ΔG and ΔS negative are at 310.15 K as well as lower and higher temperatures). Further, phospholipid phosphatidylethanolamine (a component of some viral envelops) also attaches readily with AMS and the reaction is spontaneous. AMS molecules attachment with viral phospholipids and amino-acids involved in viral infection would denature the virus and prevent its attachment to the host cell. Communicated by Ramaswamy H. Sarma

Changes of microbial diversity and volatile compounds in edible and deteriorated Qingke barley fresh noodles stored at 25 °C

SummaryMicrobial diversity and volatile compounds in Qingke barley fresh noodles (QBFN) with different storage time at 25 ± 1 °C were investigated. The results showed that Pseudomonas, Pantoea, Erwinia and Alternaria, Pyrenophora, Penicillium were the dominant microorganisms in edible QBFN (stored for 0 and 12 h), while Pantoea, Erwinia, Bacillus and Penicillium, Aspergillus were the dominant spoilage microorganisms in deteriorated QBFN (stored for 18 h). The edible QBFN have high concentration of aldehydes (61.27 μg kg−1), furan and pyrazines (60.87 μg kg−1), alcohols (49.74 μg kg−1) and ketones (29.74 μg kg−1) that give basic flavours to the QBFN. As storage time increased, the concentrations of above volatile compounds decreased, and new esters and sulphuric compounds which gave unpleasant odours to the QBFN appeared. Multivariate data analysis methods showed that 2‐pentyl‐furan, hexanal, 5‐Ethylcyclopent‐1‐enecarboxaldehy, cyclohexanol and methyl allyl sulphide, ethyl isovalerate were the main volatile compounds that make a difference in flavour between the edible and deteriorated QBFN.

Developing public health messages for non-essential food components

Foods contain a variety of essential and non-essential components. Emerging evidence suggests that both the traditional essential and some non-essential portions of foods provide health benefits. For example, vitamin A and C must be provided in the diet to prevent deficiency diseases, but what about non-vitamin A producing carotenoids, polyphenols, isothiocyanates, allyl sulfides, etc.? The weight of experimental evidence suggests that these and other dietary bioactives contribute to healthfulness. Most countries have " quantitative" Recommended Dietary Allowances (RDAs) to help guide health professionals to avoid deficiency diseases in their populations. The United States has the Dietary Reference Intakes that includes RDAs, Adequate Intakes and Upper Levels. In addition, many countries provide "qualitative" advice, such as the Dietary Guidelines for Americans, which focus more on recommendations for food pattern consumption. The amount of clinical evidence necessary for establishing an RDA is substantial. While it is possible to conduct a randomized placebo-controlled trial to establish an RDA for vitamin C, there are inherent difficulties in constructing human trials for food extracts or for dietary bioactives. Thus, the amount of evidence that can be collected for non-essential food components may be less than what is expected for the essentials. Some suggest that the "totality of the evidence" should be sufficient to drive public health messages about non-essentials. Here we address potential mechanisms for "accreditation" of bioactive food components and will address issues regarding design of studies, lack of biomarkers, challenges in funding needed research, and the consequences in inaction.

Anticancer property of allyl sulfides derived from garlic (Allium sativum L.)

Several lines of evidences imply that garlic (Allium sativum L.) is one of the potent vegetable for the cancer prevention. Fresh garlic extract, garlic powder, garlic oil, and organosulfur compounds derived from garlic have been reported to exhibit the anticancer effect through their anticarcinogenic, antimutagenic, and antitumor properties. Evidences from experimental studies, those which have been performed primarily at molecular basis with garlic are introduced in this review. Especially, we focused on allyl sulfides as promising compounds derived from garlic for cancer prevention, and discussed the anticancer properties of allyl sulfides in terms of anticarcinogenic, antimutagenic and antigenotoxic activity, induction of detoxification enzymes, cell cycle inhibition as well as induction of apoptosis.

One-pot Synthesis of Allyl Sulfides from Sulfinate Esters and Allylsilanes through Reduction of Alkoxysulfonium Intermediates

An efficient method to synthesize allyl sulfides from sulfinate esters and allylsilanes is described. Based on the reactivity of isolated allyl(methoxy)phenyl sulfonium triflate, we have developed a simple one-pot method for the allyl sulfide synthesis by S-allylation of sulfinate esters and subsequent reduction with sodium borohydride. A number of allyl sulfides were prepared by this method leaving various functional groups unreacted.

Novel analytical approach to find distinctive odor compounds from garlic cloves infested by the potato-rot nematode Ditylenchus destructor using gas chromatography–olfactometry (GC–O) with heart-cut enrichment system

The potato-rot nematode Ditylenchus destructor (Tylenchida: Anguinidae) causes severe damage to garlic production in Japan. Nematode-contaminated garlic seed cloves are often used for planting, because nematode-infested cloves are difficult to discriminate from healthy ones. To be able to find nematode-infested garlic in a nondestructive way, here this study introduced a novel analytical system of GC–O and GC–MS with heart-cut enrichment technique. The objective of this research was to find an analytical approach to identify the existence of subjectively perceptible odors which derive from the garlic infested with the nematode and to evaluate the effectiveness of those novel analytical systems. Ten odor activities associated with nematode-infested garlic were detected by the system, and “allyl methyl sulfide” and “2-methyl-1-butanol” were identified as major odor compounds (1-propanethiol was candidate). This result suggests that the novel analytical technique introduced in this study delivered sufficient data to identify the odor compounds from infested garlics. Two distinctive odor compounds might be used as indicators to detect nematode-infested garlic cloves with nondestructive way.

The Effect of Thiol Structure on Allyl Sulfide Photodegradable Hydrogels and their Application as a Degradable Scaffold for Organoid Passaging.

Intestinal organoids are useful in vitro models for basic and translational studies aimed at understanding and treating disease. However, their routine culture relies on animal-derived matrices that limit translation to clinical applications. In fact, there are few fully defined, synthetic hydrogel systems that allow for the expansion of intestinal organoids. Here, an allyl sulfide photodegradable hydrogel is presented, achieving rapid degradation through radical addition-fragmentation chain transfer (AFCT) reactions, to support routine passaging of intestinal organoids. Shear rheology to first characterize the effect of thiol and allyl sulfide crosslink structures on degradation kinetics is used. Irradiation with 365 nm light (5 mW cm-2 ) in the presence of a soluble thiol (glutathione at 15 × 10-3 m), and a photoinitiator (lithium phenyl-2,4,6-trimethylbenzoylphosphinate at 1 × 10-3 m), leads to complete hydrogel degradation in less than 15 s. Allyl sulfide hydrogels are used to support the formation of epithelial colonies from single intestinal stem cells, and rapid photodegradation is used to achieve repetitive passaging of stem cell colonies without loss in morphology or organoid formation potential. This platform could support long-term culture of intestinal organoids, potentially replacing the need for animal-derived matrices, while also allowing systematic variations to the hydrogel properties tailored for the organoid of interest.

Stress Relaxation via Covalent Dynamic Bonds in Nanogel-Containing Thiol-Ene Resins.

Functional nanogels are attractive additives for use in polymer composites. In this study, nanogels with internal allyl sulfide moieties throughout their network structure were prepared via a thiol-Michael addition reaction. The excess thiol-functionalized nanogels were less than 60 nm as discrete particles but act as room-temperature liquids in the bulk state. The reactive nanogels can be dispersed in and swollen by a thiol-ene matrix resin, which upon photopolymerization yields dramatically decreased levels of polymerization shrinkage stress. Furthermore, the postcured nanogel-modified polymers effectively relaxed applied stresses as well as enhanced toughness during exposure to a UV light source that activated the addition-fragmentation as a means for dynamic bond exchange. These nanogels provide a generic approach to introduce adaptable network performance that significantly improves a number of key properties of glassy cross-linked polymer.

Hemin Catalyzed Dealkylative Intercepted [2, 3]‐Sigmatropic Rearrangement Reactions of Sulfonium Ylides with 2, 2, 2‐Trifluorodiazoethane

AbstractA dealkylative intercepted [2, 3]‐sigmatropic rearrangement reaction of allylic sulfides with 2, 2, 2‐trifluorodiazoethane (CF3CHN2) is reported, the commercially available and biocompatible catalyst hemin was found to efficiently catalyze this transformation across a diverse set of allylic sulfides with in situ generated CF3CHN2, providing excellent yields (up to 99%) under mild condition without inert gas protection. In addition, CF3CHN2 exhibited unique reactivity toward this process compared with other frequently used diazo reagents. This work expands the range of carbene‐mediated transformations catalyzed by hemin and introduces a concise and general strategy for exploiting new possibility of reactions concerning organosulfides.magnified image

Is there any still undisclosed biodiversity in Ciauscolo salami? A new glance into the microbiota of an artisan production as revealed by high-throughput sequencing

Ciauscolo is a fermented sausage with the Protected Geographical Indication (PGI) status. To disclose the microbial ecology of a model Ciauscolo salami manufacture during its natural fermentation, viable counting, amplicon-based sequencing and real-time PCR were applied. The volatilome during fermentation was also characterized. The results allowed previously undetected species to be discovered. The core microbiota was composed by Lactobacillus algidus, Leuconostoc carnosum, Lactobacillus sakei, Debaryomyces hansenii, Glomus hyderabadensis, Tilletiopsis washingtonensis, and Kurtzmaniella zeylanoides. Salmonella spp. and Listeria monocytogenes were absent in all the samples; moreover, multiplex real-time PCR revealed the absence of the target genes bont/A, bont/B, bont/E, bont/F, and 4gyrB (CP), encoding botulinic toxins. Volatilome, deeply depending on microbiological metabolism, was characterized by spices-derived components. Limonene, sabinene, α- and β-pinene, 3-carene, and α-thujene were the most represented monoterpene hydrocarbons, whereas β- and α-copaene were the most represented sesquiterpene hydrocarbons. Allyl methyl sulphide and diallyl disulphide were the major aliphatic sulphur compounds, together with diallyl sulphide and allyl methyl disulphide.

Relaxation of Extracellular Matrix Forces Directs Crypt Formation and Architecture in Intestinal Organoids.

Intestinal organoid protocols rely on the use of extracellular scaffolds, typically Matrigel, and upon switching from growth to differentiation promoting media, a symmetry breaking event takes place. During this stage, the first bud like structures analogous to crypts protrude from the central body and differentiation ensues. While organoids provide unparalleled architectural and functional complexity, this sophistication is also responsible for the high variability and lack of reproducibility of uniform crypt-villus structures. If function follows form in organoids, such structural variability carries potential limitations for translational applications (e.g., drug screening). Consequently, there is interest in developing synthetic biomaterials to direct organoid growth and differentiation. It has been hypothesized that synthetic scaffold softening is necessary for crypt development, and these mechanical requirements raise the question, what compressive forces and subsequent relaxation are necessary for organoid maturation? To that end, allyl sulfide hydrogels are employed as a synthetic extracellular matrix mimic, but with photocleavable bonds that temporally regulate the material's bulk modulus. By varying the extent of matrix softening, it is demonstrated that crypt formation, size, and number per colony are functions of matrix softening. An understanding of the mechanical dependence of crypt architecture is necessary to instruct homogenous, reproducible organoids for clinical applications.

Control of the microsporidian parasite Nosema ceranae in honey bees (Apis mellifera) using nutraceutical and immuno-stimulatory compounds.

Nosema ceranae is a microsporidian parasite that causes nosemosis in the honey bee (Apis mellifera). As alternatives to the antibiotic fumagillin, ten nutraceuticals (oregano oil, thymol, carvacrol, trans-cinnmaldehyde, tetrahydrocurcumin, sulforaphane, naringenin, embelin, allyl sulfide, hydroxytyrosol) and two immuno-stimulatory compounds (chitosan, poly I:C) were examined for controlling N. ceranae infections. Caged bees were inoculated with N. ceranae spores, and treatments were administered in sugar syrup. Only two compounds did not significantly reduce N. ceranae spore counts compared to the infected positive control, but the most effective were sulforaphane from cruciferous vegetables, carvacrol from oregano oil, and naringenin from citrus fruit. When tested at several concentrations, the highest sulforaphane concentration reduced spore counts by 100%, but also caused 100% bee mortality. For carvacrol, the maximum reduction in spore counts was 57% with an intermediate concentration and the maximum bee mortality was 23% with the highest concentration. For naringenin, the maximum reduction in spore counts was 64% with the highest concentration, and the maximum bee mortality was only 15% with an intermediate concentration. In the longevity experiment, naringenin-fed bees lived as long as Nosema-free control bees, both of which lived significantly longer than infected positive control bees. While its antimicrobial properties may be promising, reducing sulforaphane toxicity to bees is necessary before it can be considered as a candidate for controlling N. ceranae. Although further work on formulation is needed with naringenin, its effect on extending longevity in infected bees may give it an additional value as a potential additive for bee feed in honey bee colonies.