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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 -
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 -
Angewandte Chemie (International Ed. in... Aug 2016A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was...
A set of broadly applicable methods for efficient catalytic additions of easy-to-handle allyl-B(pin) (pin=pinacolato) compounds to ketones and acyclic α-ketoesters was developed. Accordingly, a large array of tertiary alcohols can be obtained in 60 to >98 % yield and up to 99:1 enantiomeric ratio. At the heart of this development is rational alteration of the structures of the small-molecule aminophenol-based catalysts. Notably, with ketones, increasing the size of a catalyst moiety (tBu to SiPh3 ) results in much higher enantioselectivity. With α-ketoesters, on the other hand, not only does the opposite hold true, since Me substitution leads to substantially higher enantioselectivity, but the sense of the selectivity is reversed as well.
Topics: Alcohols; Allyl Compounds; Boron Compounds; Butanones; Catalysis; Esters; Ketones; Molecular Structure; Stereoisomerism
PubMed: 27273249
DOI: 10.1002/anie.201603894 -
Food Chemistry Feb 2019Maternal garlic intake during pregnancy and the breastfeeding period has been reported to be associated with the potential of modulating later garlic acceptance in...
Maternal garlic intake during pregnancy and the breastfeeding period has been reported to be associated with the potential of modulating later garlic acceptance in infants. However, the metabolism of garlic constituents in humans and their elimination and potential excretion into human milk are not yet fully understood. In previous studies, we identified volatile garlic-derived metabolites in human milk as well as in human urine, namely allyl methyl sulfide, allyl methyl sulfoxide and allyl methyl sulfone. To monitor the excretion of these garlic metabolites in a larger cohort, we quantified these metabolites in a total of 18 human milk sets, whereby each set comprised of one sample collected before and three samples after garlic consumption. The analyses revealed that the concentrations of the metabolites were most abundant 1-3.5 h after garlic consumption, with distinct differences between test persons regarding metabolite concentrations as well as temporal excretion.
Topics: Allyl Compounds; Female; Garlic; Humans; Milk, Human; Sulfides; Volatilization
PubMed: 30372984
DOI: 10.1016/j.foodchem.2018.09.039 -
International Journal of Biological... 2024Previous studies have demonstrated that diallyl disulfide (DADS) exhibits potent anti-tumor activity. However, the pharmacological actions of DADS in inhibiting the...
Previous studies have demonstrated that diallyl disulfide (DADS) exhibits potent anti-tumor activity. However, the pharmacological actions of DADS in inhibiting the growth of colorectal cancer (CRC) cells have not been clarified. Herein, we show that DADS treatment impairs the activation of the pentose phosphate pathway (PPP) to decrease PRPP (5-phosphate ribose-1-pyrophosphate) production, enhancing DNA damage and cell apoptosis, and inhibiting the growth of CRC cells. Mechanistically, DADS treatment promoted POU2F1 K48-linked ubiquitination and degradation by attenuating the PI3K/AKT signaling to up-regulate TRIM21 expression in CRC cells. Evidently, TRIM21 interacted with POU2F1, and induced the K272 ubiquitination of POU2F1. The effects of DADS on the enhanced K272 ubiquitination of POU2F1, the PPP flux, PRPP production, DNA damage and cell apoptosis as well as the growth of CRC tumors were significantly mitigated by TRIM21 silencing or activating the PI3K signaling in CRC cells. Conversely, the effects of DADS were enhanced by TRIM21 over-expression or inhibiting the PI3K/AKT signaling in CRC cells. Collectively, our findings reveal a novel mechanism by which DADS suppresses the growth of CRC by promoting POU2F1 ubiquitination, and may aid in design of novel therapeutic intervention of CRC.
Topics: Humans; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Apoptosis; Allyl Compounds; Colorectal Neoplasms; DNA Damage; Octamer Transcription Factor-1; Disulfides; 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid
PubMed: 38385081
DOI: 10.7150/ijbs.91206 -
Journal of the American Chemical Society Oct 2017A copper-catalyzed three-component linchpin coupling method for the stereoselective union of readily available epoxides and allyl electrophiles is disclosed....
A copper-catalyzed three-component linchpin coupling method for the stereoselective union of readily available epoxides and allyl electrophiles is disclosed. Transformations employ [B(pin)]-methane as a conjunctive reagent, resulting in the formation of two C-C bonds at a single carbon center bearing a C(sp) organoboron functional group. Products are obtained in 42-99% yield, and up to >20:1 dr. The utility of the approach is highlighted by stereospecific transformations entailing allylation, tandem cross coupling, and application to the synthesis 1,3-polyol motifs.
Topics: Alkenes; Allyl Compounds; Amination; Boronic Acids; Catalysis; Copper; Epoxy Compounds; Methane; Stereoisomerism
PubMed: 28934852
DOI: 10.1021/jacs.7b09309 -
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 -
Angewandte Chemie (International Ed. in... Jul 2019Herein, we report a modular synthetic route to linear and branched homoallylic amines that operates through a sequential one-pot Lewis base/transition-metal catalyzed... (Review)
Review
Herein, we report a modular synthetic route to linear and branched homoallylic amines that operates through a sequential one-pot Lewis base/transition-metal catalyzed allylic alkylation/Hofmann rearrangement strategy. This protocol is operationally trivial, proceeds from simple and easily prepared substrates and catalysts, and enables all aspects of regio- and stereoselectivity to be controlled through a conserved experimental protocol. Overall, the high levels of enantio-, regio-, and diastereoselectivity obtained, in concert with the ability to access orthogonally protected or free amines, render this a straightforward and effective approach for the preparation of useful enantioenriched homoallylic amines. We have also demonstrated the utility of the products in the context of pharmaceutical synthesis.
Topics: Alkylation; Allyl Compounds; Amines; Catalysis; Metals, Heavy; Molecular Structure; Stereoisomerism
PubMed: 31132203
DOI: 10.1002/anie.201905426 -
Journal of the American Society For... May 2015The fragmentations of argentinated N-allylbenzamides have been exhaustively studied through collision-induced dissociation and through deuterium labeling. The intriguing... (Comparative Study)
Comparative Study
The fragmentations of argentinated N-allylbenzamides have been exhaustively studied through collision-induced dissociation and through deuterium labeling. The intriguing elimination of AgOH is certified as the consequence of intramolecular cyclization between terminal olefin and carbonyl carbon following proton transfer to carbonyl oxygen, rather than simple enolization of amide. Linear free energy correlations and density functional theory (DFT) calculations were performed to understand the competitive relationship between AgOH loss and AgH loss, which results from the 1,2-elimination of α-hydrogen (to the amido nitrogen) with the silver.
Topics: Allyl Compounds; Benzamides; Catalysis; Energy Transfer; Hot Temperature; Hydroxides; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Organometallic Compounds; Silver; Silver Compounds; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Volatilization
PubMed: 25707590
DOI: 10.1007/s13361-015-1079-0 -
Molecules (Basel, Switzerland) Sep 2018In this study, the nutritional, functional, and chemical measurements of sensory attributes of different parts of wasabi, namely, leaf, petiole, and rhizome, were...
In this study, the nutritional, functional, and chemical measurements of sensory attributes of different parts of wasabi, namely, leaf, petiole, and rhizome, were investigated. Proximate composition analysis showed the presence of high amounts of carbohydrates in the rhizome and amino acid composition analysis confirmed high proportions of glutamic acid and aspartic acid in all three parts. While proximate composition showed low lipid content in wasabi, ω-3 fatty acids accounted for a high proportion (>44%) of the total lipids. Wasabi leaves had high vitamin C and total phenolic contents, and thus demonstrated antioxidant capacity. Allyl isothiocyanate, which gives wasabi its characteristic pungent taste, was identified by gas chromatography/mass spectrometry and an electronic nose. On an electronic tongue, wasabi leaves showed compounds associated with sourness and saltiness while the petiole had high content of compounds associated with sweetness and bitterness. This study provides basic data for the utilization of wasabi parts as food materials based on their nutritional, functional, and chemical measure of sensory attributes.
Topics: Allyl Compounds; Ascorbic Acid; Fatty Acids, Omega-3; Isocyanates; Plant Components, Aerial; Rhizome; Wasabia
PubMed: 30274347
DOI: 10.3390/molecules23102512