- Synthesis of rhenium(I) and technetium(I) carbonyl/dithioether ligand complexes bearing 3,17β-estradiol
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Tricarbonyldithioethermetal(I) complexes of rhenium and technetium with a pendant 3,17β-estradiol have been synthesized and characterized. The steroid ligand was bound to the metal centre by the two sulfur atoms of a 4,7-dithiaoct-1-ine spacer.
- Reisgys, Martina,Wuest, Frank,Alberto, Roger,Schibli, Roger,Schubiger, Paul August,Pietzsch, Hans-Juergen,Spies, Hartmut,Johannsen, Bernd
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Read Online
- Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives
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A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative
- Guimar?es, Keller G.,De Freitas, Rossimiriam P.,Ruiz, Ana L.T.G.,Fiorito, Giovanna F.,De Carvalho, Jo?o E.,Da Cunha, Elaine F.F.,Ramalho, Teodorico C.,Alves, Rosemeire B.
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Read Online
- Interactions of carborane-containing electrophiles with triethyl phosphite. Synthesis of new carborane-containing phosphonates
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The reactions of o-carboran-1-ylethyl mesylates with triethyl phosphite and sodium diethyl phosphite were studied. Carborane-containing phosphonates were synthesized. The reaction of o-carboranylacetyl chloride with triethyl phosphite afforded O,O-diethyl (E)-2-(o-carboran-1-yl)-1-(o-carboran-1-ylacetoxy)vinylphosphonate rather than oxo phosphonate.
- Semioskkin,Inyushin,Ermanson,Petrovskii,Lemmen,Bregadze
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Read Online
- The preparation of immunosuppressant SR-31747
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The preparation of immunosuppressant SR-31747 is described. Attempts to install the Z-allyl amine included Lindlar partial hydrogenation and vinyl stannane methodologies. Ultimately, the Wittig olefination of aidehyde 12 with the ylide derived from β-amin
- Burgess, Laurence E.
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Read Online
- A chemical labeling of N6-formyl adenosine (f6A) RNA
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N6-methyl adenosine (m6A) is an eminent epigenetic mark in mRNAs that affects a broad range of biological functions in diverse species. However, the chemically inert methyl group prevents a direct labeling of this modification for subsequent detection and sequencing. Therefore, most current approaches for the labeling of m6A still have limitations of relying on the utilization of corresponding methyltransferases, which resulted in the lacking of efficiency. Here we present an approach which selectively alkylated the N6-formyl adenosine (f6A), the key intermediate during chemical oxidation of m6A, with an alkyne functionality that can be further labeled with click reactions. This covalent labeling approach will be able to facilitate in the affinity purification, detection and genome-wide profiling studies.
- Xie, Li-Jun,Lin, Cui-Lian,Liu, Li,Cheng, Liang
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supporting information
p. 1563 - 1566
(2021/10/06)
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- Synthesis of N-alkylated pyrazolo[3,4-d]pyrimidine analogs and evaluation of acetylcholinesterase and carbonic anhydrase inhibition properties
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Fused pyrimidines, especially pyrazolo[3,4-d]pyrimidines, are among the most preferred building blocks for pharmacology studies, as they exhibit a broad spectrum of biological activity. In this study, new derivatives of pyrazolo[3,4-d]pyrimidine were synthesized by alkylation of the N1 nitrogen atom. We synthesized 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine 2 from commercially available aminopyrazolopyrimidine 1 using N-iodosuccinimide as an iodinating agent. The synthesis of compound 2 started with nucleophilic substitution of 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine with R–X (X: –OMs, –Br, –Cl), affording?N-alkylated pyrazolo[3,4-d]pyrimidine. We performed this synthesis using a weak inorganic base?and the mild temperature was also used for a two-step procedure to generate N-alkylated pyrazolo[3,4-d]pyrimidine derivatives. Also, all compounds were tested for their ability to inhibit acetylcholinesterase (AChE) and the human carbonic anhydrase (hCA) isoforms I and II, with Ki values in the range of 15.41 ± 1.39–63.03 ± 10.68 nM for AChE, 17.68 ± 1.92–66.27 ± 5.43 nM for hCA I, and 8.41 ± 2.03–28.60 ± 7.32 nM for hCA II. Notably, compound 10 was the most selective and potent CA I inhibitor with a significant selectivity ratio of 26.90.
- Aydin, Busra O.,Anil, Derya,Demir, Yeliz
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- Green one-pot four-component synthesis of 3,5-disubstituted isoxazoles- sulfonates and sulfonamides using a combination of NaDCC as metal-free catalyst and ultrasonic activation in water
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A simple and green one-pot reaction has been proposed for the synthesis of novel 3,5-disubstituted isoxazole-sulfonates and -sulfonamides (5a-j) in water under ultrasound irradiation. The methodology is based on the use of safe and environmentally friendly reagents and allows, via in-situ 1,3-dipolar cycloaddition, an easy access to functionalized heterocycles with the creation of four new bonds (S[sbnd]O, C[sbnd]N, C[sbnd]O and C[sbnd]C). Comparison studies using classical magnetic stirring and ultrasound irradiation clearly showed that sonication promoted clean transformation, high yields (72–89%) and faster reactions (20–28 min). All the synthesized compounds were fully characterized by MS-ES, 1H NMR, 13C NMR spectroscopy and HPLC analysis.
- Talha, Aicha,Tachallait, Hamza,Benhida, Rachid,Bougrin, Khalid
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supporting information
(2021/09/13)
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- Convenient Continuous Flow Synthesis of N-Methyl Secondary Amines from Alkyl Mesylates and Epoxides
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The first continuous flow process was developed to synthesize N-methyl secondary amines from alkyl mesylates and epoxides via a nucleophilic substitution using aqueous methylamine. A variety of N-methyl secondary amines were produced in good to excellent yields, including a number of bioactive compounds or their precursors. Up to 10.6 g (88% yield) of an N-methyl secondary amine was produced in 140 min process time. The amination procedure included an in-line workup, and the starting mesylate material was also produced in continuous flow from the corresponding alcohol. Finally, an in-line process combining the mesylate synthesis and nucleophilic substitution was developed.
- Lebel, Hélène,Mathieu, Gary,Patel, Heena
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p. 2157 - 2168
(2020/11/23)
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- Efficient synthesis of organic thioacetates in water
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Thioacetates as precursors of thiols are interesting starting points for synthesizing other organosulfur compounds. Herein, we propose a simple, efficient and fast method to obtain organic thioacetates using water as a solvent. Taking into account the great attention that has been paid toward environmentally friendly synthetic procedures in the past decades, we prove the role and the strength of the thioacetate anion as a nucleophile for nucleophilic displacement reactions in an aqueous medium. The reactions were carried out under pH control, to prevent the decomposition of the mesylate starting materials, using potassium carbonate as a safe and mild base. A simple work up allows products to be obtained with excellent yield and acceptable purity.
- Olivito,Costanzo,Di Gioia,Nardi,Oliverio,Procopio
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supporting information
p. 7753 - 7759
(2018/11/02)
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- Benzazepine Dicarboxamide Compounds
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This invention relates to novel benzazepine dicarboxamide compounds of the formula wherein R1 to R4 are as defined in the description and in the claims, as well as pharmaceutically acceptable salts thereof. These compounds are TLR agonists and may therefore be useful as medicaments for the treatment of diseases such as cancer, autoimmune diseases, inflammation, sepsis, allergy, asthma, graft rejection, graft-versus-host disease, immunodeficiencies, and infectious diseases.
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Paragraph 0361; 0362
(2016/09/26)
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- The design of 8-hydroxyquinoline tetracyclic lactams as HIV-1 integrase strand transfer inhibitors
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A novel series of HIV-1 integrase strand transfer inhibitors were designed using the venerable two-metal binding pharmacophore model and incorporating structural elements from two different literature scaffolds. This manuscript describes a number of 8-hyd
- Velthuisen, Emile J.,Johns, Brian A.,Temelkoff, David P.,Brown, Kevin W.,Danehower, Susan C.
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- Palladium(II)-Catalyzed Regioselective syn-Hydroarylation of Disubstituted Alkynes Using a Removable Directing Group
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A palladium(II)-catalyzed regioselective syn-hydroarylation reaction of homopropargyl amines has been developed, wherein selectivity is controlled by a cleavable bidentate directing group. Under the optimized reaction conditions, both dialkyl and alkylaryl alkyne substrates were found to undergo hydroarylation with high selectivity. The products of this reaction contain a 4,4-disubstituted homoallylic amine motif that is commonly seen in drug molecules and other bioactive compounds.
- Liu, Zhen,Derosa, Joseph,Engle, Keary M.
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supporting information
p. 13076 - 13081
(2016/10/13)
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- Inhibition of NaV1.6 sodium channel currents by a novel series of 1,4-disubstituted-triazole derivatives obtained via copper-catalyzed click chemistry
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We have synthesized and evaluated a series of 1,4-disubstituted-triazole derivatives for inhibition of the rat NaV1.6 sodium channel isoform, an isoform thought to play an important role in controlling neuronal firing. Starting from a series of 2,4(1H)-diarylimidazoles previously published, we decided to extend the SAR study by replacing the imidazole with a different heterocyclic scaffold and by varying the aryl substituents on the central aromatic ring. The 1,4-disubstituted 1,2,3-triazoles were prepared employing the copper-catalyzed azide-alkyne cycloaddition (CuAAC). Many of the new molecules were able to block the rNav1.6 currents at 10 μM by over 20%, displaying IC50 values ranging in the low micromolar, thus indicating that triazole can efficiently replace the central heterocyclic core. Moreover, the introduction of a long chain at C4 of the central triazole seems beneficial for increased rNav1.6 current block, whereas the length of N1 substituent seems less crucial for inhibition, as long as a phenyl ring is not direcly connected to the triazole. These results provide additional information on the structural features necessary for block of the voltage-gated sodium channels. These new data will be exploited in the preparation of new compounds and could result in potentially useful AEDs.
- Rivara, Mirko,Patel, Manoj K.,Amori, Laura,Zuliani, Valentina
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supporting information
p. 6401 - 6404
(2012/10/29)
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- Influence of the acetylenic substituent on the intramolecular carbolithiation of alkynes
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The intramolecular carbolithiation of a series of propargylic ethers has been performed to evaluate the influence of the terminal substituent on the efficiency and the stereochemical outcome of the cyclization. Our results show that only 5-exo-dig cyclizations are observed, and dihydrobenzofurans are obtained exclusively. Depending on the nature of the terminal substituent, two cases can be considered. If the terminal substituent carried by the acetylenic carbon atom is itself a carbon atom, the cyclization can occur provided the terminal propargylic position bears a coordinating element and is at least disubstituted. When the cyclization occurs, it follows an anti-carbolithiation pathway and thus leads to the E isomer of the exocyclic double bond. Only in one case (Ph) was a mixture of the E and Z isomers of the resulting olefin recovered. The cyclization can also take place if the alkyne is directly substituted by S or Si, provided the cyclization conditions are tuned. In the case of the trimethylsilyl substituent, a syn-carbolithiation was observed. If the double bond is recovered, in most cases, in the exocyclic position, the products can aromatize directly for SPh-substituted substrate 24. Furthermore, in the two latter cases, when alkylation of the vinyllithium intermediate is performed, isomerization of the double bond seems instantaneous. Copyright
- Girard, Anne-Lise,Lhermet, Rudy,Fressigne, Catherine,Durandetti, Muriel,Maddaluno, Jacques
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scheme or table
p. 2895 - 2905
(2012/06/29)
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- Synthesis and reactivity of dipropargylic disulfides: tandem rearrangements, cyclization, and oxidative dimerization
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Synthesis and facile rearrangement and cyclization reaction of new dipropargylic disulfides are described. A possible mechanism for these transformations involving an initial double [2,3]-sigmatropic rearrangement to the elusive diallenyl disulfides via a thiosulfoxide intermediates is suggested.
- Braverman, Samuel,Cherkinsky, Marina,Meridor, David,Sprecher, Milon
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scheme or table
p. 1925 - 1930
(2010/04/24)
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- NOVEL SYNTHETIC BINDING PAIRS AND USES THEREOF
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Cucurbituril assemblies, polyamine structures capable of binding thereto, affinity pairs of cucurbituril assemblies and such polyamine structures and methods utilizing same are disclosed.
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Page/Page column 70
(2010/02/11)
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- The use of Sonogashira coupling for the synthesis of modified uracil peptide nucleic acid
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Palladium-catalyzed Sonogashira coupling has been shown to be compatible with PNA monomers as illustrated by the reaction of 5-iodouracil peptide nucleic acid monomer (IU-PNA) with several terminal alkynes. These reactions have been performed in the solution phase and with IU-PNA linked to an insoluble polymer support. The results presented herein show that while the isolated yields from the solution phase chemistry are modest (38-53%), the yields of the resin-bound coupling reactions are essentially quantitative, at the monomer level. A selection of alkynes was used to install various additional functionality on the uracil nucleobase. Examples of a hydroxyl, protected thiol and protected amino group are given. Further, an example of derivatization of a resin-bound oligomer with a single IU insert is given.
- Hudson, Robert H.E,Li, Ge,Tse, Joseph
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p. 1381 - 1386
(2007/10/03)
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- Phthalazine derivatives phosphodiesterase 4 inhibitors
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The present invention provides a compound selected from the group including: 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-4-phenyl-phthalazine; 4-(3,5-dichloro-pyridin-4-ylmethyl)-7-methoxy-1H-phthalazin-2-carboxylic acid methyl ester; benzyl-{3-{1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl}-prop-2-ynyl}-methyl-amine; 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-5-(5-morpholin-4-yl-pent-1-ynyl)-phthalazine dihydrochloride; 3-{1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-phthalazin-5-yl}-prop-2-yn-1-ol; 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-4-morpholin-4-yl-phthalazine; 1-(3,5-dichloro-pyridin-4-ylmethyl)-6-methoxy-4-(1,2,4)triazol-1-yl-phthalazine; N→O derivatives thereof; and pharmaceutically acceptable salts thereof. The invention also provides a pharmaceutical composition which includes a therapeutically effective amount of the above compound in admixture with a suitable carrier.
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- Carbonyl propargylation by 1-substituted prop-2-ynyl mesylates and carbonyl allenylation by 3-substituted prop-2-ynyl mesylates with tin(II) iodide and tetrabutylammonium iodide
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1-Substituted prop-2-ynyl mesylates cause propargylation of aldehydes with tin(II) iodide, tetrabutylammonium iodide and sodium iodide in 1,3-dimethylimidazolidin-2-one to produce 2-substituted but-3-yn-1-ols, while 3-substituted prop-2-ynyl mesylates cau
- Masuyama,Watabe,Ito,Kurusu
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p. 2009 - 2010
(2007/10/03)
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- Process for producing 1-substituted-hydantoins
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The subject is to provides a process for producing 1-substituted-hydantoins of Formula I: STR1 wherein R1 represents d hydrocarbon group which may be substituted and others, cheracterized by reacting N-sustituted-N-alkcycarbonylamnilo-acetonitrile of Formula II: STR2 wherein R2 represents an alkyl group and others, with an alkali metal hydroxides or the like and then treating with an acid.
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- Process for producing 1-substituted-hydantoins
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The subject is to provides a process for producing 1-substituted-hydantoins of Formula I: wherein R1represents a hydrocarbon group which may be substituted and others,characterized by reacting N-substituted-N-alkoxycarbonylamino-acetonitrile of Formula II: wherein R2represents an alkyl group and others,with an alkali metal hydroxides or the like and then treating with an acid.
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- Practical and Safe Sulfonylation of 2-Alkynyl and 2-Alkenyl Alcohols Using the Combined Bases of a Catalytic Amount of Tertiary Amine and Potassium Carbonate
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Several 2-alkynyl and 2-alkenyl alcohols were effectively sulfonylated with methanesulfonyl chloride or p-toluenesulfonyl chloride using the combined bases of a catalytic amount of tertiary amine and potassium carbonate.The reaction was conducted with reliable safety and while avoiding the disposal of wasted amines.The mesylation of 2-propyn-1-ol proceeded on a large scale (more than 20 kg) without a substantial production of explosive 3-chloro-1-propyne.The choice of the catalysts was important, and sterically unhindered tertiary amines, such as trimethylamine, N,N-d imethylbenzylamine, and triethylamine, were effective.Without these catalysts the reactions were significantly retarded.The reaction was so mild that it could be applied to complex and optically active 4-hydroxy-3-methyl-2-(2-propynyl)-2-cyclopenten-1-one, which is an important alcohol moiety of synthetic pyrethroids.
- Tanabe, Yoo,Yamamoto, Hitomi,Yoshida, Yoshihiro,Miyawaki, Takashi,Utsumi, Naoka
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p. 297 - 300
(2007/10/02)
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- The Stereochemistry of Organometallic Compounds. XXXII. Hydrocyanation of Derivatives of Amino Alkynes
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The hydrocyanation of a range of amino alkyne derivatives has been studied by using nickel-based catalyst systems.The phthalimido derivatives have been shown to give good yields of unsaturated cyano amine derivatives, and some of these have been converted into both saturated and unsaturated amino acids.
- Jackson, W. Roy,Perlmutter, Patrick,Smallridge, Andrew J.
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p. 1201 - 1208
(2007/10/02)
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- SYNTHESE D'ALCOHOLS α-ALLENIQUES PAR REACTION D'ORGANOCHROMIQUES PROPARGYLIQUES SUR LES ALDEHYDES ET LES CETONES
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Propargylic bromides can be condensed with aldehydes and ketones in the presence of Hiyama's reagent (2CrCl3+LiAlH4 in THF) leading to α-allenic alcohols, to homopropargylic alcohols or to the mixture of both of them.The selectivity (or specificity) of this reaction depends on the substitution of the propargylic bromide, on the structure of the ketone, and on the presence of HMPT in the reaction mixture.In many cases, α- allenic alcohol has been specifically or very selectively obtained.The mechanism of the reaction and the influence of the various parameters are discussed.
- Place, Pierre,Verniere, Catherine,Gore, Jacques
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p. 1359 - 1368
(2007/10/02)
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