-
Chemical Reviews Apr 2021Asymmetric allylic alkylation mediated by transition metals provides an efficient strategy to form quaternary stereogenic centers. While this transformation is dominated... (Review)
Review
Asymmetric allylic alkylation mediated by transition metals provides an efficient strategy to form quaternary stereogenic centers. While this transformation is dominated by the use of second- and third-row transition metals (e.g., Pd, Rh, and Ir), recent developments have revealed the potential of first-row transition metals, which provide not only a less expensive and potentially equally efficient alternative but also new mechanistic possibilities. This review summarizes examples for the assembly of quaternary stereocenters using prochiral allylic substrates and hard, achiral nucleophiles in the presence of copper complexes and highlights the complementary approaches with soft, prochiral nucleophiles catalyzed by chiral cobalt and nickel complexes.
Topics: Alkylation; Allyl Compounds; Catalysis; Coordination Complexes; Ligands; Solvents; Stereoisomerism; Structure-Activity Relationship; Temperature; Transition Elements
PubMed: 33570909
DOI: 10.1021/acs.chemrev.0c01115 -
Dental Materials : Official Publication... Apr 2014Thiol- and allyl-functionalized siloxane oligomers are synthesized and evaluated for use as a radical-mediated, rapid set elastomeric dental impression material....
OBJECTIVES
Thiol- and allyl-functionalized siloxane oligomers are synthesized and evaluated for use as a radical-mediated, rapid set elastomeric dental impression material. Thiol-ene siloxane formulations are crosslinked using a redox-initiated polymerization scheme, and the mechanical properties of the thiol-ene network are manipulated through the incorporation of varying degrees of plasticizer and kaolin filler. Formulations with medium and light body consistencies are further evaluated for their ability to accurately replicate features on both the gross and microscopic levels. We hypothesize that thiol-ene functionalized siloxane systems will exhibit faster setting times and greater detail reproduction than commercially available polyvinylsiloxane (PVS) materials of comparable consistencies.
METHODS
Thiol-ene functionalized siloxane mixtures formulated with varying levels of redox initiators, plasticizer, and kaolin filler are made and evaluated for their polymerization speed (FTIR), consistency (ISO4823.9.2), and surface energy (goniometer). Feature replication is evaluated quantitatively by SEM. The Tg, storage modulus, and creep behavior are determined by DMA.
RESULTS
Increasing redox initiation rate increases the polymerization rate but at high levels also limits working time. Combining 0.86 wt% oxidizing agent with up to 5 wt% plasticizer gave a working time of 3 min and a setting time of 2 min. The selected medium and light body thiol-ene formulations also achieved greater qualitative detail reproduction than the commercial material and reproduced micrometer patterns with 98% accuracy.
SIGNIFICANCE
Improving detail reproduction and setting speed is a primary focus of dental impression material design and synthesis. Radical-mediated polymerizations, particularly thiol-ene reactions, are recognized for their speed, reduced shrinkage, and 'click' nature.
Topics: Allyl Compounds; Cross-Linking Reagents; Dental Impression Materials; Elastomers; Kaolin; Materials Testing; Polymerization; Polymers; Siloxanes; Sulfhydryl Reagents
PubMed: 24553250
DOI: 10.1016/j.dental.2014.01.011 -
Current Drug Metabolism 2015Diallyl sulfide (DAS) and other organosulfur compounds are chief constituents of garlic. These compounds have many health benefits, as they are very efficient in... (Review)
Review
Diallyl sulfide (DAS) and other organosulfur compounds are chief constituents of garlic. These compounds have many health benefits, as they are very efficient in detoxifying natural agents. Therefore, these compounds may be useful for prevention/treatment of cancers. However, DAS has shown appreciable allergic reactions and toxicity, as they can also affect normal cells. Thus their use as in the prevention and treatment of cancer is limited. DAS is a selective inhibitor of cytochrome P450 2E1 (CYP2E1), which is known to metabolize many xenobiotics including alcohol and analgesic drugs in the liver. CYP2E1-mediated alcohol/drug metabolism produce reactive oxygen species and reactive metabolites, which damage DNA, protein, and lipid membranes, subsequently causing liver damage. Several groups have shown that DAS is not only capable of inhibiting alcohol- and drug-mediated cellular toxicities, but also HIV protein- and diabetes-mediated toxicities by selectively inhibiting CYP2E1 in various cell types. However, due to known DAS toxicities, its use as a treatment modality for alcohol/drug- and HIV/diabetes-mediated toxicity have only limited clinical relevance. Therefore, effort is being made to generate DAS analogs, which are potent and selective inhibitor of CYP2E1 and poor substrate of CYP2E1. This review summarizes current advances in the field of DAS, its anticancer properties, role as a CYP2E1 inhibitor, preventing agent of cellular toxicities from alcohol, analgesic drugs, xenobiotics, as well as, from diseases like HIV and diabetes. Finally, this review also provides insights toward developing novel DAS analogues for chemical intervention of many disease conditions by targeting CYP2E1 enzyme.
Topics: Allyl Compounds; Analgesics; Animals; Antineoplastic Agents; Cytochrome P-450 CYP2E1; Cytoprotection; Ethanol; Humans; Protective Agents; Sulfides; Xenobiotics
PubMed: 26264202
DOI: 10.2174/1389200216666150812123554 -
Nature May 2016New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of...
New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as "classics". Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact.
Topics: Allyl Compounds; Biological Products; Carbon; Chemistry Techniques, Synthetic; Electrochemistry; Green Chemistry Technology; Hydrogen; Oxidants; Oxidation-Reduction; Substrate Specificity
PubMed: 27096371
DOI: 10.1038/nature17431 -
Journal of the American Chemical Society Mar 2016We report the first 1,3-dipolar cycloadditions of 1,2-cyclohexadiene, a rarely exploited strained allene. 1,2-Cyclohexadiene is generated in situ under mild conditions...
We report the first 1,3-dipolar cycloadditions of 1,2-cyclohexadiene, a rarely exploited strained allene. 1,2-Cyclohexadiene is generated in situ under mild conditions and trapped with nitrones to give isoxazolidine products in synthetically useful yields. The reactions occur regioselectively and exhibit a notable endo preference, thus resulting in the controlled formation of two new bonds and two stereogenic centers. DFT calculations of stepwise and concerted reaction pathways are used to rationalize the observed selectivities. Moreover, the strategic manipulation of nitrone cycloadducts demonstrates the utility of this methodology for the assembly of compounds bearing multiple heterocyclic units. These studies showcase the exploitation of a traditionally avoided reactive intermediate in chemical synthesis.
Topics: Allyl Compounds; Cycloaddition Reaction; Cyclohexenes; Heterocyclic Compounds; Nitrogen Oxides; Stereoisomerism
PubMed: 26854652
DOI: 10.1021/jacs.5b13304 -
The FEBS Journal Jan 2012Natural allyl sulfur compounds show antiproliferative effects on tumor cells, but the biochemical mechanisms underlying the antitumorigenic properties of the organ...
Natural allyl sulfur compounds show antiproliferative effects on tumor cells, but the biochemical mechanisms underlying the antitumorigenic properties of the organ sulfur compounds are not yet fully understood. Sodium 2-propenyl-thiosulfate is a garlic water-soluble organo-sulfane sulfur compound able to promote apoptosis in cancer cells, affecting the 'managing' of the redox state in the cell. Our studies show that sodium 2-propenyl-thiosulfate reacts spontaneously with reduced glutathione at physiological pH, leading to the formation of S-allyl-mercapto-glutathione, radicals and peroxyl species, which are able to induce inhibition of enzymes with cysteine in the catalytic site, such as sulfurtransferases. S-Allyl-mercapto-glutathione was purified and characterized by NMR and MS, and its cytotoxic effect at 500 μm on HuT 78 cells was analyzed, showing activation of the p38-MAPK pathway. Many allyl sulfur compounds are also able to promote chemoprevention by induction of xenobiotic-metabolizing enzymes, inducing down-activation or detoxification of the carcinogens. Thus, the effects of the S-allyl-mercapto-glutathione on proteins involved in the cellular detoxification system, such as glutathione S-transferase, have been evaluated both in vitro and in HuT 78 cells. Although the antitumor properties of water-soluble sulfur compounds may arise from several mechanisms and it is likely that more cellular events occur simultaneously, a relevant role is played by the formation of both reduced glutathione conjugates and radical species that affect the activity of the thiol-proteins involved in fundamental cellular processes.
Topics: Allyl Compounds; Apoptosis; Blotting, Western; Cell Cycle; Cell Proliferation; Fluorescence; Glutathione; Humans; Lymphoma, T-Cell; Magnetic Resonance Spectroscopy; Oxidation-Reduction; Sulfuric Acid Esters; Tumor Cells, Cultured
PubMed: 22035263
DOI: 10.1111/j.1742-4658.2011.08407.x -
Angewandte Chemie (International Ed. in... Feb 2017Chiral biphenols catalyze the asymmetric Petasis borono-Mannich allylation of aldehydes and amines through the use of a bench-stable allyldioxaborolane. The reaction...
Chiral biphenols catalyze the asymmetric Petasis borono-Mannich allylation of aldehydes and amines through the use of a bench-stable allyldioxaborolane. The reaction proceeds via a two-step, one-pot process and requires 2-8 mole % of 3,3'-Ph -BINOL as the optimal catalyst. Under microwave heating the reaction affords chiral homoallylic amines in excellent yields (up to 99 %) and high enantioselectivies (er up to 99:1). The catalytic reaction is a true multicomponent condensation reaction whereas both the aldehyde and the amine can possess a wide range of structural and electronic properties. Use of crotyldioxaborolane in the reaction results in stereodivergent products with anti- and syn-diastereomers both in good diastereoselectivities and enantioselectivities from the corresponding E- and Z-borolane stereoisomers.
Topics: Aldehydes; Allyl Compounds; Amines; Boronic Acids; Catalysis; Mannich Bases; Naphthols; Phenols; Stereoisomerism
PubMed: 28052567
DOI: 10.1002/anie.201611332 -
Oxidative Medicine and Cellular... 2020Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on...
Allylmethylsulfide (AMS) is a novel sulfur metabolite found in the garlic-fed serum of humans and animals. In the present study, we have observed that AMS is safe on chronic administration and has a potential antihypertrophic effect. Chronic administration of AMS for 30 days did not cause any significant differences in the body weight, electrocardiogram, food intake, serum biochemical parameters, and histopathology of vital organs. Single-dose pharmacokinetics of AMS suggests that AMS is rapidly metabolized into Allylmethylsulfoxide (AMSO) and Allylmethylsulfone (AMSO). To evaluate the efficacy of AMS, cardiac hypertrophy was induced by subcutaneous implantation of ALZET® osmotic minipump containing isoproterenol (~5 mg/kg/day), cotreated with AMS (25 and 50 mg/kg/day) and enalapril (10 mg/kg/day) for 2 weeks. AMS and enalapril significantly reduced cardiac hypertrophy as studied by the heart weight to body weight ratio and mRNA expression of fetal genes (ANP and -MHC). We have observed that TBARS, a parameter of lipid peroxidation, was reduced and the antioxidant enzymes (glutathione, catalase, and superoxide dismutase) were improved in the AMS and enalapril-cotreated hypertrophic hearts. The extracellular matrix (ECM) components such as matrix metalloproteinases (MMP2 and MMP9) were significantly upregulated in the diseased hearts; however, with the AMS and enalapril, it was preserved. Similarly, caspases 3, 7, and 9 were upregulated in hypertrophic hearts, and with the AMS and enalapril treatment, they were reduced. Further to corroborate this finding with data, we have checked the nuclear expression of caspase 3/7 in the H9c2 cells treated with isoproterenol and observed that AMS cotreatment reduced it significantly. Histopathological investigation of myocardium suggests AMS and enalapril treatment reduced fibrosis in hypertrophied hearts. Based on our experimental results, we conclude that AMS, an active metabolite of garlic, could reduce isoproterenol-induced cardiac hypertrophy by reducing oxidative stress, apoptosis, and stabilizing ECM components.
Topics: Allyl Compounds; Animals; Antioxidants; Apoptosis; Biomarkers; Body Weight; Cardiomegaly; Caspases; Cell Line; Extracellular Matrix; Fibrosis; Garlic; Isoproterenol; Lipid Peroxidation; Male; Matrix Metalloproteinases; Myoblasts; Organ Size; Rats, Sprague-Dawley; Reactive Oxygen Species; Sulfides
PubMed: 32617142
DOI: 10.1155/2020/7856318 -
Journal of Agricultural and Food... Aug 2005In support of a new clinical trial designed to compare the effects of crushed fresh garlic and two types of garlic supplement tablets (enteric-coated dried fresh garlic...
In support of a new clinical trial designed to compare the effects of crushed fresh garlic and two types of garlic supplement tablets (enteric-coated dried fresh garlic and dried aged garlic extract) on serum lipids, the three garlic products have been characterized for (a) composition (14 sulfur and 2 non-sulfur compounds), (b) stability of suspected active compounds, and (c) availability of allyl thiosulfinates (mainly allicin) under both simulated gastrointestinal (tablet dissolution) conditions and in vivo. The allyl thiosulfinates of blended fresh garlic were stable for at least 2 years when stored at -80 degrees C. The dissolution release of thiosulfinates from the enteric-coated garlic tablets was found to be >95%. The bioavailability of allyl thiosulfinates from these tablets, measured as breath allyl methyl sulfide, was found to be complete and equivalent to that of crushed fresh garlic. S-Allylcysteine was stable for 12 months at ambient temperature. The stability of the suspected active compounds under the conditions of the study and the bioavailability of allyl thiosulfinates from the dried garlic supplement have validated the use of these preparations for comparison in a clinical trial.
Topics: Allyl Compounds; Biological Availability; Breath Tests; Clinical Trials as Topic; Condiments; Dietary Supplements; Disulfides; Drug Stability; Garlic; Humans; Placebos; Sulfides; Sulfinic Acids; Sulfur Compounds; Time Factors
PubMed: 16076102
DOI: 10.1021/jf050536+ -
Nature Communications Sep 2021Spirocycles play an important role in drug discovery and development. The direct, catalytic, and enantioselective synthesis of spirocycles from readily available...
Spirocycles play an important role in drug discovery and development. The direct, catalytic, and enantioselective synthesis of spirocycles from readily available starting materials and in an atom economic manner remains a highly sought-after task in organic synthesis. Herein, an enantioselective Pd-hydride-catalyzed cycloaddition method for the synthesis of spirocyclic compounds directly from two classes of commonly available starting materials, 1,3-enynes and cyclic carbon-hydrogen (C-H) bonds, is reported. The reactions employ a chiral Pd/WingPhos catalyst to both suppress the formation of bis-allenyl by-products and control the stereoselectivity. 1,3-Enynes are used as dielectrophilic four-carbon units in the cycloaddition reactions, which also enables an enyne substrate-directed enantioselectivity switch with good levels of stereocontrol. The present spirocycle synthesis tolerates a broad range of functional groups of 1,3-enyne substrates, including alcohols, esters, nitriles, halides, and olefins. A variety of diverse cyclic nucleophiles, including pharmaceutically important heterocycles and carbocycles, can be flexibly incorporated with spiro scaffolds.
Topics: Allyl Compounds; Catalysis; Cycloaddition Reaction; Molecular Structure; Palladium; Stereoisomerism
PubMed: 34580311
DOI: 10.1038/s41467-021-25981-x