- Metabolically stable vanillin derivatives for the treatment of hypoxia
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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.
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Page/Page column 12; 15-16
(2021/09/01)
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- An investigation of structure‐activity relationships of azolylacryloyl derivatives yielded potent and long‐acting hemoglobin modulators for reversing erythrocyte sickling
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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
- Abdulmalik, Osheiza,El‐araby, Moustafa E.,Ghatge, Mohini S.,Muhammad, Yosra A.,Omar, Abdelsattar M.,Paredes, Steven D.,Safo, Martin K.
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- Synthesis of (: Z)-β-halo α,β-unsaturated carbonyl systems via the combination of halotrimethylsilane and tetrafluoroboric acid
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A convenient and broadly applicable method for the hydrohalogenation of ynones is described, by the combination of halotrimethylsilanes and tetrafluoroboric acid. Practically, one equivalent of HX (Br?nsted acid) and BF3 (Lewis acid) is smoothly generated, which activates the carbonyl compounds. Through this protocol, 42 examples of (Z)-β-halovinyl carbonyl compounds (Cl, Br and I) were obtained, in good yields and high stereoselectivity having 2-MeTHF as a solvent.
- Da Silva, Vitor A. F.,Da Silva, Gustavo P.,Matsuo, Bianca T.,Ali, Akbar,Davis, Rebecca L.,Zukerman-Schpector, Julio,Corrêa, Arlene G.,Paix?o, Márcio W.
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supporting information
p. 519 - 526
(2019/01/24)
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- Cascade and Effective Syntheses of Functionalized Tellurophenes
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A one-pot and transition-metal-catalyst-free synthetic strategy to construct functionalized tellurophenes has been developed. Substituted 1,1-dibromo-1-en-3-ynes are smoothly converted to tellurophenes with telluride salts in high yield via a series of cascade reactions through reductive debromination, hydrotelluration, nucleophilic cyclization, and aromatization. Close inspection of the results clearly showed that the reactivity of in situ prepared telluride salts are significantly influenced by the polarity of the solvent system and the electronic nature of the substituent on the enyne substrate. This method reports the first direct synthesis of 3-aryltellurophenes in high yields at room temperature. This novel reaction strategy is also found to be a promising synthetic method for multisubstituted tellurophenes and selenophenes.
- Karapala, Vamsi Krishna,Shih, Hong-Pin,Han, Chien-Chung
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supporting information
p. 1550 - 1554
(2018/03/23)
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- Gem-Digold Acetylide Complexes for Catalytic Intermolecular [4 + 2] Cycloaddition: Having Two Gold Centers Is Better for Asymmetric Catalysis
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Gold(I)-catalyzed highly enantioselective intermolecular [4 + 2] cycloaddition is shown with ynones and cyclohexadiene. Various bicyclo[2.2.2]octadiene derivatives are produced in high yields (up to 99%) with good enantioselectivity (up to 96% ee). Key to the success is generation of the gem-digold terminal alkyne as a catalytic on-cycle species. As proof of the gem-digold catalysis, a positive nonlinear effect is clarified between the ee's of the ligand and the cycloadduct.
- Nanko, Masaki,Shibuya, Satoru,Inaba, Yuya,Ono, Soichiro,Ito, Shigekazu,Mikami, Koichi
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supporting information
p. 7353 - 7357
(2018/10/15)
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- β-Silyl-Assisted Tandem Diels-Alder/Nazarov Reaction of 1-Aryl-3-(trimethylsilyl) Ynones
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A one-pot tandem Diels-Alder/Nazarov reaction of 1-aryl-3-(trimethylsilyl) ynones has been achieved to generate carbo- and heterocyclic fused ring systems in good to excellent yields. The β-silyl effect is instrumental in accessing this otherwise challenging cascade annulation reaction. The tandem reaction proceeds in the presence of BCl3 to generate three new carbon-carbon bonds, a quaternary carbon, and two stereogenic centers with excellent diastereocontrol. A variety of substituted arenes, and even heteroaromatics, are tolerated to provide tricyclic products that are of interest as advanced intermediates toward biologically relevant compounds.
- Carmichael, Rachael A.,Sophanpanichkul, Punyanuch,Chalifoux, Wesley A.
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supporting information
p. 2592 - 2595
(2017/05/24)
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- Consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz syntheses of tri- and tetrasubstituted pyridines
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The concatenation of the modified Sonogashira alkynone synthesis and the Bagley-Bohlmann-Rahtz pyridine synthesis gives novel consecutive three- and four-component coupling-Bagley-Bohlmann-Rahtz (cBBR) syntheses of tri- and tetrasubstituted pyridines in a one-pot fashion. With these processes 15 differently substituted 3-ethoxycarbonyl 2-methylpyridines can be readily obtained in modest to moderate yields.
- Dohe, Janis,Müller, Thomas J. J.
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p. 705 - 718
(2016/07/06)
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- Condensation reactions of guanidines with bis-electrophiles: Formation of highly nitrogenous heterocycles
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2-Amino-1,4-dihydropyrimidines were reacted with bis-electrophiles to produce novel fused bipyrimidine, pyrimidoaminotriazine, and pyrimidosulfonamide scaffolds. In addition, a quinazoline library was constructed using a guanidine Atwal-Biginelli reaction with 1-(quinazolin-2-yl)guanidines. The product heterocycles have novel constitutions with high nitrogen atom counts and represent valuable additions to screening libraries for the discovery of new modulators of biological targets.
- Arnold, David M.,Laporte, Matthew G.,Anderson, Shelby M.,Wipf, Peter
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p. 7719 - 7731
(2013/08/23)
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- Synthesis of ynones via recyclable polystyrene-supported palladium(0) complex catalyzed acylation of terminal alkynes with acyl chlorides under copper- and solvent-free conditions
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Herein, a highly efficient method for the copper- and solvent-free coupling reaction of acyl chlorides and terminal alkynes catalyzed by 1-phenyl-1,2-propanedione-2-oxime thiosemicarbazone-functionalized polystyrene resin-supported Pd(0) complex is descri
- Bakherad, Mohammad,Keivanloo, Ali,Bahramian, Bahram,Jajarmi, Saeideh
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experimental part
p. 311 - 314
(2011/04/12)
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- Chiral propargyl alcohols via the enantioselective addition of terminal Di- and triynes to aldehydes
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The enantioselective addition of di- and triynes to aldehydes is presented, including the first examples of an asymmetric triyne addition. Modification of the Carreira alkynylation protocol shows that addition of diynes and triynes to α-branched aldehydes can be complete in as little as 4 h, and these reactions give good yields and enantioselectivities (up to 98% ee) for di- and triynes tested (aryl, alkyl, and silyl). It is shown for two cases (20 and 24) that products of this asymmetric addition reaction can undergo further manipulation (desilylation and triazole formation) without affecting the enantiopurity.
- Graham, Erin R.,Tykwinski, Rik R.
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scheme or table
p. 6574 - 6583
(2011/10/05)
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- One-pot three-step synthesis of 1,2,3-triazoles by copper-catalyzed cycloaddition of azides with alkynes formed by a Sonogashira cross-coupling and desilylation
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A microwave-assisted, one-pot, three-step Sonogashira cross-coupling- desilylation-cycloaddition sequence was developed for the convenient preparation of 1,4-disubstituted 1,2,3-triazoles starting from a range of halides, acyl chlorides, ethynyltrimethyls
- Friscourt, Frederic,Boons, Geert-Jan
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supporting information; experimental part
p. 4936 - 4939
(2010/12/25)
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- Synthesis and stereochemical resolution of functional [5]pericyclynes
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Three different kinds of ring carbo-mers of [5]cyclitol ethers were targeted as challenging examples of functional [5]pericyclynes. Three tertiary pentaaryl-carbo-[5]cyclitol methyl ethers were synthesized through a [11+4] ring-closing double addition of
- Maurette, Luc,Tedeschi, Christine,Sermot, Emmanuelle,Soleilhavoup, Michle,Hussain, Fatima,Donnadieu, Bruno,Chauvin, Remi
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p. 10077 - 10098
(2007/10/03)
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- New Entry to a Three-Component Pyrimidine Synthesis by TMS-Ynones via Sonogashira Coupling
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(Equation presented) TMS-ynones are versatile synthetic equivalents of β-keto aldehydes and can be readily synthesized in an atom-economical fashion by coupling (het)aroyl chlorides and (TMS)-acetylene with only one equiv (!) of triethylamine under Sonogashira conditions. This mild ynone synthesis is also a suitable entry to 2,4-disubstituted pyrimidines in the sense of a one-pot three-component reaction, i.e., a coupling-addition- cyclocondensation sequence.
- Karpov, Alexei S.,Mueller, Thomas J. J.
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p. 3451 - 3454
(2007/10/03)
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- Straightforward Novel One-Pot Enaminone and Pyrimidine Syntheses by Coupling-Addition-Cyclocondensation Sequences
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The coupling of acid chlorides 1 with terminal alkynes 2 using only one equivalent (!) of triethylamine under Sonogashira conditions followed by subsequent addition of primary or secondary amines 4 to the intermediate alkynones 3 represents a straight-for
- Karpov, Alexei S.,Mueller, Thomas J. J.
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p. 2815 - 2826
(2007/10/03)
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- Synthesis of unsymmetrically substituted 1,3-butadiynes and 1,3,5-hexatriynes via alkylidene carbenoid rearrangements
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Unsymmetrically substituted 1,3-butadiynes and 1,3,5-hexatriynes are synthesized in four steps from commercially available aldehydes or carboxylic acids. The key step in this process involves a Fritsch-Buttenberg-Wiechell rearrangement, in which an alkylidene carbenoid intermediate subsequently rearranges to the desired polyyne. This rearrangement proceeds under mild conditions, and it is tolerant of a range of functionalities. In general, the procedurally facile formation of the dibromoolefinic precursors, in combination with the effectiveness of the rearrangement step, makes this procedure an attractive alternative to traditional methods for di- and triyne synthesis that utilize palladium or copper catalysis.
- Shi Shun, Annabelle L. K.,Chernick, Erin T.,Eisler, Sara,Tykwinski, Rik R.
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p. 1339 - 1347
(2007/10/03)
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- Modification of the Fritsch-Buttenberg-Wiechell rearrangement: A facile route to unsymmetrical butadiynes
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A modification of the Fritsch-Buttenberg-Wiechell rearrangement has been used to form unsymmetrically substituted 1,3-butadiynes from 1,1-dibromo-olefin precursors. The reaction proceeds via lithium-halogen exchange, followed by migration of the aryl or alkynyl moiety to provide the butadiyne framework. The facile formation of the dibromo-olefins in three steps from commercially available aryl aldehydes or carboxylic acid chlorides makes this procedure an attractive alternative to traditional methods for butadiyne synthesis.
- Chernick, Erin T,Eisler, Sara,Tykwinski, Rik R
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p. 8575 - 8578
(2007/10/03)
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- The Synthesis of Electron Donor-acceptor Substituted Pyrazoles
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A variety of 1,3- and 1,5-donor-acceptor substituted pyrazole derivatives have been synthesized by the cyclocondensation of α,β-ethynyl ketones with substituted phenyl hydrazines.The regioselectivity of the cyclization depends on the reaction conditions in a manner consistent with competitive 1,2- and 1,4-addition followed by ring closure. 1,4-disubstituted derivatives can be prepared from the corresponding 4-iodopyrazole using palladium catalyzed carbon-carbon bond forming reactions.The pyrazole chromophores are expected to show interesting nonlinear optical properties.
- Miller, R. D.,Reiser, O.
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p. 755 - 764
(2007/10/02)
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- REACTION OF ALKYNYLTRIMETHYLSILANES WITH A HYPERVALENT ORGANOIODINE COMPOUND: A NEW GENERAL SYNTHESIS OF ALKYNYLIODONIUM SALTS
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New general methods for the synthesis of alkynyl(phenyl)iodonium tetrafluoroborate 2 from alkynyltrimethylsilanes 1 utilizing the combination of iodosylbenzene and triethyloxonium tetrafluoroborate or boron trifluoride etherate were developed.The medium e
- Ochiai, Masahito,Kunishima, Munetaka,Sumi, Kenzo,Nagao, Yoshimitsu,Fujita, Eiichi,et al.
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p. 4501 - 4504
(2007/10/02)
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