16469-68-4Relevant articles and documents
Mono-Gold(I)-Catalyzed Enantioselective Intermolecular Reaction of Ynones with Styrenes: Tandem Diels–Alder and Ene Sequence
Nanko, Masaki,Inaba, Yuya,Sekine, Keisuke,Mikami, Koichi
, (2021)
Gold-catalyzed intermolecular reaction leading to dihydronaphthalene derivatives in one pot from two equivalents of ynones with respect to styrene is uncovered. The [4+2] Diels–Alder cycloaddition of ynones and styrenes is catalyzed by a mono-gold(I) complex and the conjugated acid to provide an unstable 3,8a-dihydronaphthalene to subsequently undergo an intermolecular ene-type reaction with the π-activated ynone to afford multi-component coupling dihydronaphthalene products. Linear relationships between chiral ligand-gold complexes and chiral dihydronaphthalene products proves mono-gold catalysis that triggers an asymmetric tandem Diels–Alder and ene reaction sequence.
Troponoids can inhibit growth of the human fungal pathogen Cryptococcus neoformans
Donlin, Maureen J.,Zunica, Anthony,Lipnicky, Ashlyn,Garimallaprabhakaran, Aswin K.,Berkowitz, Alex J.,Grigoryan, Alexandre,Meyers, Marvin J.,Tavis, John E.,Murellic, Ryan P.
, (2017)
Cryptococcus neoformans is a pathogen that is common in immunosuppressed patients. It can be treated with amphotericin B and fluconazole, but the mortality rate remains 15 to 30%. Thus, novel and more effective anticryptococcal therapies are needed. The troponoids are based on natural products isolated from western red cedar, and have a broad range of antimicrobial activities. Extracts of western red cedar inhibit the growth of several fungal species, but neither western red cedar extracts nor troponoid derivatives have been tested against C. neoformans. We screened 56 troponoids for their ability to inhibit C. neoformans growth and to assess whether they may be attractive candidates for development into anticryptococcal drugs. We determined MICs at which the compounds inhibited 80% of cryptococcal growth relative to vehicle-treated controls and identified 12 compounds with MICs ranging from 0.2 to 15 μM. We screened compounds with MICs of ≤20 μM for cytotoxicity in liver hepatoma cells. Fifty percent cytotoxicity values (CC50s) ranged from 4 to >100 μM. The therapeutic indexes (TI, CC50/MIC) for most of the troponoids were fairly low, with most being 8, including a tropone with a TI of >300. These tropones are fungicidal and are not antagonistic when used in combination with fluconazole or amphotericin B. Inhibition by these two tropones remains unchanged under conditions favoring cryptococcal capsule formation. These data support the hypothesis that troponoids may be a productive scaffold for the development of novel anticryptococcal therapies.
Metabolically stable vanillin derivatives for the treatment of hypoxia
-
Page/Page column 12; 15; 16, (2021/09/01)
Vanillin derivative compounds that bind covalently with hemoglobin are provided. Methods of treating sickle cell disease and other hypoxia-related disorders by administering such compounds are also provided.
Enantioselective [3 + 2] annulation of 4-isothiocyanato pyrazolones and alkynyl ketones under organocatalysis
Wang, Wenyao,Wei, Shiqiang,Bao, Xiaoze,Nawaz, Shah,Qu, Jingping,Wang, Baomin
, p. 1145 - 1154 (2021/02/16)
An asymmetric [3 + 2] annulation reaction of 4-isothiocyanato pyrazolones with alkynyl ketones in the presence of an organic catalyst derived from a cinchona alkaloid under mild conditions is realized. This protocol provides unprecedented expeditious access to a wide range of optically active spiro[pyrroline-pyrazolones] with various electronic properties in high yields with good to excellent enantioselectivities.
An investigation of structure‐activity relationships of azolylacryloyl derivatives yielded potent and long‐acting hemoglobin modulators for reversing erythrocyte sickling
Abdulmalik, Osheiza,El‐araby, Moustafa E.,Ghatge, Mohini S.,Muhammad, Yosra A.,Omar, Abdelsattar M.,Paredes, Steven D.,Safo, Martin K.
, p. 1 - 21 (2020/11/09)
Aromatic aldehydes that bind to sickle hemoglobin (HbS) to increase the protein oxygen affinity and/or directly inhibit HbS polymer formation to prevent the pathological hypoxia‐induced HbS polymerization and the subsequent erythrocyte sickling have for s
Laccase-mediated Oxidations of Propargylic Alcohols. Application in the Deracemization of 1-arylprop-2-yn-1-ols in Combination with Alcohol Dehydrogenases
González-Granda, Sergio,Méndez-Sánchez, Daniel,Lavandera, Iván,Gotor-Fernández, Vicente
, p. 520 - 527 (2019/11/16)
The catalytic system composed by the laccase from Trametes versicolor and the oxy-radical TEMPO has been successfully applied in the sustainable oxidation of fourteen propargylic alcohols. The corresponding propargylic ketones were obtained in most cases in quantitative conversions (87–>99 % yield), demonstrating the efficiency of the chemoenzymatic methodology in comparison with traditional chemical oxidants, which usually lead to problems associated with the formation of by-products. Also, the stereoselective reduction of propargylic ketones was studied using alcohol dehydrogenases such as the one from Ralstonia species overexpressed in E. coli or the commercially available evo-1.1.200, allowing the access to both alcohol enantiomers mostly with complete conversions and variable selectivities depending on the aromatic pattern substitution (97–>99 % ee). To demonstrate the compatibility of the laccase-mediated oxidation and the alcohol dehydrogenase-catalyzed bioreduction, a deracemization strategy starting from the racemic compounds was developed through a sequential one-pot two-step process, obtaining a selection of (S)- or (R)-1-arylprop-2-yn-1-ols with excellent yields (>98 %) and selectivities (>98 % ee) depending on the alcohol dehydrogenase employed.
A sustainable access to ynones through laccase/TEMPO-catalyzed metal- and halogen-free aerobic oxidation of propargylic alcohols in aqueous medium
Silva, Alana B.V.,Silva, Emmanuel D.,dos Santos, Alcindo A.,Princival, Jefferson L.
, (2020/02/04)
Tuning laccase/TEMPO-catalyzed aerobic oxidation of secondary propargylic alcohols in aqueous media was accomplished in order to efficiently synthesize ynones. This study led to the formulation of an effective and sustainable catalytic method for the preparation of mono- and bis-substituted ynones compared with traditional oxidative methods.
Relay Catalysis to Synthesize β-Substituted Enones: Organocatalytic Substitution of Vinylogous Esters and Amides with Organoboronates
Sundstrom, Sasha,Nguyen, Thien S.,May, Jeremy A.
, p. 1355 - 1359 (2020/02/13)
Organocatalysis was shown to facilitate conjugate additions to vinylogous esters and amides for the first time. Subsequent elimination of a β-alcohol or amine provided π-conjugated β-substituted enones. Remarkably, nucleophile addition to the electron-rich vinylogous substrates is more rapid than classical enones, forming monosubstituted products. A doubly organocatalytic (organic diol and methyl aniline) conjugate addition synthesized the products directly from alkynyl ketones. Both of these catalytic transformations are orthogonal to transition metal catalysis, allowing for good yields, easily accessible or commercially available reagents, high selectivity, reagent recovery and recyclability, facile scalability, and exceptional functional group tolerance.
Covalent Adaptable Networks with Tunable Exchange Rates Based on Reversible Thiol–yne Cross-Linking
Du Prez, Filip E.,Guerre, Marc,Maes, Diederick,Unal, Kamil,Van Herck, Niels,Winne, Johan M.
, p. 3609 - 3617 (2020/02/04)
The design of covalent adaptable networks (CANs) relies on the ability to trigger the rearrangement of bonds within a polymer network. Simple activated alkynes are now used as versatile reversible cross-linkers for thiols. The click-like thiol–yne cross-linking reaction readily enables network synthesis from polythiols through a double Michael addition with a reversible and tunable second addition step. The resulting thioacetal cross-linking moieties are robust but dynamic linkages. A series of different activated alkynes have been synthesized and systematically probed for their ability to produce dynamic thioacetal linkages, both in kinetic studies of small molecule models, as well as in stress relaxation and creep measurements on thiol–yne-based CANs. The results are further rationalized by DFT calculations, showing that the bond exchange rates can be significantly influenced by the choice of the activated alkyne cross-linker.
Cracking under internal pressure: Photodynamic behavior of vinyl azide crystals through N2release
Shields, Dylan J.,Karothu, Durga Prasad,Sambath, Karthik,Ranaweera, Ranaweera A. A. Upul,Schramm, Stefan,Duncan, Alexander,Duncan, Benjamin,Krause, Jeanette A.,Gudmundsdottir, Anna D.,Naumov, Pan?e
, p. 18565 - 18575 (2020/12/01)
When exposed to UV light, single crystals of the vinyl azides 3- azido-1-phenylpropenone (1a), 3-azido-1-(4-methoxyphenyl)propenone (1b), and 3-azido-1-(4-chlorophenyl)propenone (1c) exhibit dramatic mechanical effects by cracking or bending with the release of N2. Mechanistic studies using laser flash photolysis, supported by quantum mechanical calculations, show that each of the vinyl azides degrades through a vinylnitrene intermediate. However, despite having very similar crystal packing motifs, the three compounds exhibit distinct photomechanical responses in bulk crystals. While the crystals of 1a delaminate and release gaseous N2 indiscriminately under paraffin oil, the crystals of 1b and 1c visibly expand, bend, and fracture, mainly along specific crystallographic faces, before releasing N2. The photochemical analysis suggests that the observed expansion is due to internal pressure exerted by the gaseous product in the crystal lattices of these materials. Lattice energy calculations, supported by nanoindentation experiments, show significant differences in the respective lattice energies. The calculations identify critical features in the crystal structures of 1b and 1c where elastic energy accumulates during gas release, which correspond to the direction of the observed cracks. This study highlights the hitherto untapped potential of photochemical gas release to elicit a photomechanical response and motility of photoreactive molecular crystals.
