- Enantioselective Reductive Cyanation and Phosphonylation of Secondary Amides by Iridium and Chiral Thiourea Sequential Catalysis
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The combination of transition-metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α-aminonitriles and α-aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α-functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused.
- Chen, Dong-Huang,Sun, Wei-Ting,Zhu, Cheng-Jie,Lu, Guang-Sheng,Wu, Dong-Ping,Wang, Ai-E,Huang, Pei-Qiang
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supporting information
p. 8827 - 8831
(2021/03/16)
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- Hydrogen-Bond Catalysis of Imine Exchange in Dynamic Covalent Systems
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The reversibility of imine bonds has been exploited to great effect in the field of dynamic covalent chemistry, with applications such as preparation of functional systems, dynamic materials, molecular machines, and covalent organic frameworks. However, acid catalysis is commonly needed for efficient equilibration of imine mixtures. Herein, it is demonstrated that hydrogen bond donors such as thioureas and squaramides can catalyze the equilibration of dynamic imine systems under unprecedentedly mild conditions. Catalysis occurs in a range of solvents and in the presence of many sensitive additives, showing moderate to good rate accelerations for both imine metathesis and transimination with amines, hydrazines, and hydroxylamines. Furthermore, the catalyst proved simple to immobilize, introducing both reusability and extended control of the equilibration process.
- Schaufelberger, Fredrik,Seigel, Karolina,Ramstr?m, Olof
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supporting information
p. 15581 - 15588
(2020/10/02)
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- A designed and potentially decadentate ligand for use in lanthanide(iii) catalysed biomass transformations: Targeting diastereoselective: Trans -4,5-diaminocyclopentenone derivatives
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The goal of this study was to design a ligand system which can accommodate single lanthanide(iii)-ions and investigate the properties of the resulting complexes. The complexes of all the accesible lanthanides and yttrium with the new ligand LH6 = N,N′-dimethyl-N,N′-ethylene-bis(5-bromo-3-(1H-benzimidazol-2-yl)hydrazineylidene)-2-hydroxybenzylamine) were obtained in high yield at room temperature under aerobic reaction conditions. The corresponding compounds were characterised using X-ray diffraction, FT-IR, elemental analysis and the optical properties of all complexes were investigated using UV-vis and fluorescence spectroscopy. The air stable complexes efficiently transform biomass furfural to trans-4,5-cyclopentenones in high yield.
- Fuhr, Olaf,Merkel, Marcel P.,Peewasan, Krisana,Powell, Annie K.
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supporting information
p. 2331 - 2336
(2020/02/26)
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- Homoallylic amines as efficient chiral inducing frameworks in the conjugate addition of amides to α,β-unsaturated esters. An entry to enantio-enriched diversely substituted amines
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The diastereoselective conjugate addition of secondary homoallylamines, obtained in the enantioenriched form via allylmetallation of imines, to α,β-unsaturated esters is reported. This method allows access to valuable building blocks as well as heterocyclic skeletons, providing tertiary amines bearing two chains integrating a stereogenic center adjacent to the nitrogen atom.
- Anani, Lilia,Behr, Jean-Bernard,Coelho, Aurélien,Machado-Rodrigues, Carine,Massicot, Fabien,Rogier, Johann,Vasse, Jean-Luc
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supporting information
p. 2632 - 2636
(2020/04/17)
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- Synthesis and Cytotoxicity of Octahydroepoxyisoindole-7-carboxylic Acids and Norcantharidin–Amide Hybrids as Norcantharidin Analogues
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Octahydroepoxyisoindole analogues of norcantharidin were accessed through a Diels–Alder reaction of an amine-substituted furan with maleic anhydride and subsequent reduction of the bicyclo[2.2.1]heptene olefin. Despite retention of the carboxylate and the ether bridgehead known to impart cytotoxic activity to norcantharidin, none of these analogues displayed notable cytotoxicity against the 11 cell lines examined: HT29 (colon), MCF-7 (breast), A2780 (ovarian), H460 (lung), A431 (skin), Du145 (prostate), BE2-C (neuroblastoma), SJ-G2 and U87 (glioblastoma), MIA (pancreatic), and SMA (spontaneous murine astrocytoma). The incorporation of an amino-substituted system post-synthesis of norcantharidin afforded facile access to 14 acid/amide-substituted norcantharidin analogues. Of these, only four displayed sufficient activity at the initial 25 μm compound screening dose to warrant full evaluation of growth inhibition. Common to these analogues was the presence of a 4-biphenyl moiety, and in particular 3-(2-(furan-2-ylmethyl)-3-(4-biphenylamino)-3-oxopropylcarbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid (13 c) and 3-(2-(pyrrole-2-ylmethyl)-3-(4-biphenylamino)-3-oxopropylcarbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid (24) displayed high levels of cytotoxicity, returning GI50 values of 15 nm (HT29) to 2.9 μm (U87) and 17 nm (SMA) to 2.8 μm (U87), respectively. These are the most cytotoxic norcantharidin analogues reported to date.
- Hizartzidis, Lacey,Gilbert, Jayne,Gordon, Christopher P.,Sakoff, Jennette A.,McCluskey, Adam
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supporting information
p. 1152 - 1161
(2019/05/24)
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- Activation of primary amines by copper(i)-based lewis acid promoters in the solventless synthesis of secondary propargylamines
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Primary amines are activated by copper(I)-based Lewis acid promoters in an A 3 -coupling one-pot solventless reaction with aldehydes and phenylacetylene for the synthesis of secondary propargylamines. The reaction is promoted by a CuSO 4 /NaI system, a practical precursor of the in situ generated effective CuI/I 2 system, that worked well, but only in a restricted number of examples. Substitution of I 2 with CeCl 3 ·7H 2 O in a one-pot two-step reaction provided good yields and a wider applicability, with the added value given by a safer procedure.
- Cimarelli, Cristina,Navazio, Federica,Rossi, Federico V.,Del Bello, Fabio,Marcantoni, Enrico
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p. 2387 - 2396
(2019/05/27)
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- Improving C=N bond reductions with (Cyclopentadienone)iron complexes: Scope and limitations
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Herein, we broaden the application scope of (cyclo-pentadienone)iron complexes 1 in C=N bond reduction. The catalytic scope of pre-catalyst 1b, which is more active than the “Kn?lker complex” (1a) and other members of its family, has been expanded to the catalytic transfer hydrogenation (CTH) of a wider range of aldimines and ketimines, either pre-isolated or generated in situ. The kinetics of 1b-promoted CTH of ketimine S1 were assessed, showing a pseudo-first order profile, with TOF = 6.07 h–1 at 50 % conversion. Moreover, the chiral complex 1c and its analog 1d were employed in the enantioselective reduction of ketimines and reductive amination of ketones, giving fair to good yields and moderate enantioselectivity.
- Cettolin, Mattia,Bai, Xishan,Lübken, Dennis,Gatti, Marco,Facchini, Sofia Vailati,Piarulli, Umberto,Pignataro, Luca,Gennari, Cesare
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supporting information
p. 647 - 654
(2018/10/24)
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- Nucleophilic Imines and Electrophilic o-Quinone Methides, a Three-Component Assembly of Assorted 3,4-Dihydro-2 H-1,3-benzoxazines
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A one-pot method for joining three separate components leading to an assortment of N-substituted 3,4-dihydro-2H-1,3-benzoxazines is described. The method involves the addition of a Grignard reagent to an o-OBoc salicylaldehyde in the presence of an imine. With a variety of components, 15 examples are presented, including the diastereoselective incorporation of chiral imines.
- Chen, Peishan Kc,Wong, Yuk Fai,Yang, Derek,Pettus, Thomas R. R.
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supporting information
p. 7746 - 7749
(2019/10/11)
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- Copper(II) Triflate As a Reusable Catalyst for the Synthesis of trans-4,5-Diamino-cyclopent-2-enones in Water
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trans-4,5-Diamino-cyclopent-2-enones (CP) are usually prepared by Lewis acid-catalyzed condensation of furfural and a secondary amine in an organic solvent. The reaction proceeds through the formation of a Stenhouse salt (SS) intermediate followed by an electrocyclization reaction to afford the desired CP. Herein, we described the use of Cu(OTf)2 as a very efficient catalyst for the synthesis of CP in water at room temperature. Furthermore, the mild reaction conditions, catalyst reusability, and outstanding functional group tolerance suggest that this CP platform can be further used in chemical biology.
- Gomes, Rafael F. A.,Esteves, Nuno R.,Coelho, Jaime A. S.,Afonso, Carlos A. M.
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supporting information
p. 7509 - 7513
(2018/07/29)
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- Ruthenium-Catalyzed C-H Arylation and Alkenylation of Furfural Imines with Boronates
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A Ru0-catalyzed direct C-H arylation and alkenylation of furfural imines with aryl- or alkenyl-boronates, in the presence of benzylideneacetone as a sacrificial hydride acceptor, is disclosed. This reaction provides access, after hydrolysis, to C3-arylated or vinylated furfural derivatives, and thus valorizes these relevant building-blocks obtained from lignocellulosic biomass. This approach, involving C-H activation by a Ru0/RuII, cycle offers several advantages, notably simple, mild and neutral reaction conditions.
- Siopa, Filipa,Ramis Cladera, Valérie-Anne,Afonso, Carlos Alberto Mateus,Oble, Julie,Poli, Giovanni
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supporting information
p. 6101 - 6106
(2018/09/18)
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- Biorenewable deep eutectic solvent for selective and scalable conversion of furfural into cyclopentenone derivatives
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The development of novel synthetic routes to produce bioactive compounds starting from renewable sources has become an important research area in organic and medicinal chemistry. Here, we present a low-cost procedure for the tunable and selective conversion of biomass-produced furfural to cyclopentenone derivatives using a mixture of choline chloride and urea as a biorenewable deep eutectic solvent (DES). The proposed medium is a nontoxic, biodegradable, and could be reused up to four times without any unfavorable effect on the reaction yield. The process is tunable, clean, cheap, simple and scalable and meets most of the criteria; therefore, it can be considered as an environmental sustainable process in a natural reaction medium.
- Di Gioia, Maria Luisa,Nardi, Monica,Costanzo, Paola,De Nino, Antonio,Maiuolo, Loredana,Oliverio, Manuela,Procopio, Antonio
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- Preparation of homoallylic amines via a three-component coupling process
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A three-component synthesis of homoallylic amines is described. The allylboronic species were generated in situ by homologation of vinyl boroxines with trimethylsilyldiazomethane, then followed by trapping of the allylboron intermediate with imines. Twenty-seven compounds were successfully prepared in moderate to high yields. Imines bearing various functional groups were tolerated, including aliphatic, aromatic and heteroaromatic substituents. Further elaboration of some of the homoallylic amines to form azeditines is also reported.
- Battilocchio, Claudio,Labes, Ricardo,Ley, Steven V.,Ou, Xiaoxu
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supporting information
p. 6652 - 6654
(2018/09/29)
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- A metallopeptoid as an efficient bioinspired cooperative catalyst for the aerobic oxidative synthesis of imines
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Enzymatic catalysis is largely based on intramolecular cooperativity between a metal center and functional organic molecules located on one scaffold. Inspired by this concept we have designed the metallopeptoid trimer BT, which is a unique intramolecular cooperative oxidation catalyst incorporating two catalytic centers, phenanthroline-copper and TEMPO, as well as one non-catalytic benzyl group. Herein we explore the capability of BT to act as an efficient catalyst for the oxidative synthesis of imines, which are versatile intermediates in the fine chemicals and pharmaceutical industries. We demonstrate that BT, combined with CuI, can catalyze the production of benzyl, aryl, heteroaryl, allylic and aliphatic imines from various alcohols and amines with a turn-over-number up to 45 times higher than this achieved when phenanthroline, copper and TEMPO are mixed in solution. Moreover, in low catalyst(s) loading, BT enables transformations that are not possible when a mixture of the individual catalysts is employed.
- Chandra Mohan, Darapanani,Sadhukha, Arghya,Maayan, Galia
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p. 139 - 144
(2017/10/16)
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- Murai Reaction on Furfural Derivatives Enabled by Removable N,N′-Bidentate Directing Groups
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Furfural and related compounds are industrially relevant building blocks obtained from lignocellulosic biomass. To enhance the added value of these renewable resources, a Ru-catalyzed hydrofurylation of alkenes, involving a directed C?H activation at C3 of the furan ring, was developed. A thorough experimental study revealed that a bidentate amino-imine directing group enabled the desired coupling. Removal of the directing group occurred during the purification step, directly releasing the C3-functionalized furfurals. Development of the reaction as well as optimization and scope of the method were described. A mechanism was proposed on the basis of DFT calculations.
- Pezzetta, Cristofer,Veiros, Luis F.,Oble, Julie,Poli, Giovanni
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supporting information
p. 8385 - 8389
(2017/06/28)
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- Synthesis, characterization, cytotoxicity and antimicrobial studies on Bi(III) dithiocarbamate complexes containing furfuryl group and their use for the preparation of Bi2O3nanoparticles
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Bismuth(III) dithiocarbamate complexes, tris(N-furfuryl-N-propyldithiocarbamato-S,S')bismuth(III) (1), tris(N-furfuryl-N-butyldithiocarbamato-S,S')bismuth(III) (2) and tris(N-furfuryl-N-benzyldithiocarbamato-S,S')bismuth(III) (3), have been prepared and characterized by microanalysis, and spectroscopy (IR and NMR). Structure of 3 has been obtained by single crystal X-ray diffraction. This complex contains distorted pentagonal pyramidal Bi(III) centres which attain an overall distorted pentagonal bipyramidal coordination via long range intermolecular Bi?S interactions. DFT quantum mechanical studies of 3 were carried out, supporting the partial double bond character of C–N (thioureide) and C–S bonds in dithiocarbamate ligands. All the compounds have been screened against a panel of microbes viz. Vibrio cholerae, Bacillus subtilis, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus, Aspergillus niger and Candida albicans. Complexes 1 and 3 were found to have better activity against K. pneumoniae, V. cholerae, A. niger and C. albicans than the complex 2. Complexes 1–3 have been evaluated for their in vitro cytotoxic activity against KB cells. Complexes 1 and 3 showed higher activity than 2. Bi2O3obtained from thermal decomposition of 3 has been characterized by PXRD, HRTEM, EDAX, UV–Vis and Fluorescence spectroscopy. PXRD study showed that the sample is composed of monoclinic phase of α-Bi2O3. Photocatalytic activity of as-prepared α-Bi2O3was determined by decolourization of rhodamine-B in aqueous solution under ultra violet irradiation.
- Tamilvanan, Sundaramoorthy,Gurumoorthy, Govindasamy,Thirumaran, Subbiah,Ciattini, Samuele
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- Method for synthesizing imine through cross-coupling of hydroxylation phenanthroline copper complex/O2 catalytic oxidation alcohol and amine
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The invention discloses a method for synthesizing imine through cross-coupling of hydroxylation phenanthroline copper complex/O2 catalytic oxidation alcohol and amine. According to the method, an economical and cheap hydroxylation phenanthroline copper complex is selected as a catalyst, green O2 is selected as an oxidizing agent, cross-coupling of alcohol and amine is realized under the condition of normal temperature, alkali and an expensive free radical of nitroxide is prevented from being used, and a series of imine compounds are successfully prepared. The method provided by the invention is high in reaction selectivity and relatively wide in a substrate application range, and has a great industrial application potential.
- -
-
Paragraph 0017; 0032; 0033
(2017/12/02)
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- Palladium-catalyzed vicinal amino alcohols synthesis from allyl amines by in situ tether formation and carboetherification
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Vicinal amino alcohols are important structural motifs of bioactive compounds. Reported herein is an efficient method for their synthesis based on the palladium-catalyzed oxy-alkynylation, oxy-arylation, or oxy-vinylation of allylic amines. High regio- and stereoselectivity were ensured through the in situ formation of a hemiaminal tether using the cheap commercially available trifluoroacetaldehyde in its hemiacetal form. The obtained compounds are important building blocks, which can be orthogonally deprotected to give either free alcohols, amines, or terminal alkynes.
- Orcel, Ugo,Waser, Jerome
-
supporting information
p. 5250 - 5254
(2015/04/27)
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- Palladium-catalyzed [4 + 2] cycloaddition of aldimines and 1,4-dipolar equivalents via amphiphilic allylation
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The combination of Pd catalyst and diethylzinc with triethylborane promotes the amphiphilic allylation of aldimines with 2,3-bismethylenebutane-1,4-diol derivatives to serve as bis-allylic zwitterion species to form 3,4-bismethylenepiperidines via a formal [4 + 2] cycloaddition reaction. 3,4-Bismethylenepiperidine rings are applicable for the synthesis of isoquinoline derivatives via the Diels-Alder reaction followed by an oxidation reaction with DDQ.
- Hirata, Goki,Yamada, Naoshi,Sanada, Shohei,Onodera, Gen,Kimura, Masanari
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supporting information
p. 600 - 603
(2015/03/04)
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- Trans-Symmetric Dynamic Covalent Systems: Connected Transamination and Transimination Reactions
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The development of chemical transaminations as a new type of dynamic covalent reaction is described. The key 1,3-proton shift is under complete catalytic control and can be conducted orthogonally to, or simultaneous with, transimination in the presence of an amine to rapidly yield two-dimensional dynamic systems with a high degree of complexity evolution. The transamination-transimination systems are proven to be fully reversible, stable over several days, compatible with a range of functional groups, and highly tunable. Kinetic studies show transamination to be the rate-limiting reaction in the network. Furthermore, it was discovered that readily available quinuclidine is a highly potent catalyst for aldimine transaminations. This study demonstrates how connected dynamic reactions give rise to significantly larger systems than the unconnected counterparts, and shows how reversible isomerizations can be utilized as an effective diversity-generating element. Constant exchange: The development of chemical transaminations as a new type of dynamic covalent reactions is described (see figure). This study demonstrates how connected dynamic reactions give rise to significantly larger systems than the unconnected counterparts, and shows how reversible isomerizations can be utilized as an effective diversity-generating element.
- Schaufelberger, Fredrik,Hu, Lei,Ramstr?m, Olof
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p. 9776 - 9783
(2015/06/30)
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- Morphology-tuned exceptional catalytic activity of porous-polymer-supported Mn3O4 in aerobic sp3 C-H bond oxidation of aromatic hydrocarbons and alcohols
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Mn3O4 nanomaterials with different morphologies (sphere, nanowire, and octahedron) embedded into functionalized nanoporous polymers were developed by a facile one-pot solvothermal technique at different temperatures. These Mn3O4-based hybrid materials could behave as heterogeneous nanocatalysts to perform sp3 C-H bond oxidation of aromatic hydrocarbons and alcohols with molecular oxygen as an economic oxidant. Catalytic activity could be effectively tuned by changing the morphology of incorporated Mn3O4 in nanoporous polymer. These Mn3O4-based hybrid materials exhibited remarkable catalytic performance for sp3 C-H bond oxidation as compared with bare Mn3O4 nanoparticles. Mn3O4 with octahedral morphology in nanoporous polymer exhibited the highest catalytic activity on account of its more exposed crystallographic planes and edges. These Mn3O4-based nanocatalysts could be recycled and reused for consecutive catalytic cycles without a significant loss of catalytic activity. Exceptional crystal facets: Nanoporous-polymer-supported Mn3O4 nanocatalysts (Mn@DVTA, DVTA=divinyltriallyl) with different morphologies are developed to catalyze aerobic sp3 C-H bond oxidation of aromatic hydrocarbons and alcohols. Among the different nanocatalysts, those with octahedral crystallite morphology exhibit outstanding catalytic performance.
- Mondal, John,Borah, Parijat,Sreejith, Sivaramapanicker,Nguyen, Kim Truc,Han, Xiguang,Ma, Xing,Zhao, Yanli
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p. 3518 - 3529
(2015/04/16)
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- Palladium meditated CPhenyl-H bond activation of 2-furylimines versus tert-2-furylbenzylamines
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The reactions of 2-furylimines 2a-f and Na2PdCl4 in the presence of NaOAc at 8-10°C result in nitrogen-palladium coordinated complexes 3a-f. Reduction of 2d-f with NaBH4 followed by N-methylation leads to the corresponding tert-2-furylbenzylamines 5a-c. Treatment of 5a-c with Na2PdCl4 at the same reaction condition as mentioned above affords palladacycles 6a-c where the Pd atoms connect to the phenyl ring rather than the furyl ring. The fact that 5a-c are more active than 2d-f in CPhenyl-H bond activation implies that the electron density of C10 or C8 atom in former is higher than those in latter. Compounds 3a-f, 5a-c, 6a-c were identified by elemental analysis, IR and NMR. In addition, the structures of 3b, 3f and 6c were also confirmed by their single crystal X-ray diffractions.
- Hu, Zhao-Xia,Ma, Nan,Zhang, Jin-Hua,Hu, Wen-Ping,Wang, Hong-Xing
-
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- Selective aerobic oxidation of alcohols to aldehydes, carboxylic acids, and imines catalyzed by a Ag-NHC complex
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Silver NHC catalysts have been developed for the selective oxidation of alcohols to aldehydes or carboxylic acids in the presence of BnMe3NOH or KOH under dry air. The aerobic oxidation conditions are mild, and the yield is excellent. Further tandem catalysis enables the one-pot synthesis of imines in excellent yield. Only 0.1 mol % of the catalyst is required.
- Han, Lei,Xing, Ping,Jiang, Biao
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supporting information
p. 3428 - 3431
(2014/07/21)
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- Stereoselective synthesis of γ-lactams from imines and cyanosuccinic anhydrides
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A reaction between imines and anhydrides has been developed with chiral disubstituted anhydrides and chiral imines. The synthesis of highly substituted γ-lactams with three stereogenic centers, including one quaternary center, proceeds at room temperature in high yield and with high diastereoselectivity in most cases. Enantiomerically pure alkyl-substituted anhydrides proceed with no epimerization, thus providing access to enantiomerically pure penta-substituted lactam products.
- Tan, Darlene Q.,Younai, Ashkaan,Pattawong, Ommidala,Fettinger, James C.,Cheong, Paul Ha-Yeon,Shaw, Jared T.
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supporting information
p. 5126 - 5129
(2013/10/22)
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- Selective imine formation from alcohols and amines catalyzed by polymer incarcerated gold/palladium alloy nanoparticles with molecular oxygen as an oxidant
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Carbon black stabilized, polymer incarcerated gold/palladium alloy nanoparticles (PICB-Au/Pd) act as an efficient, reusable heterogeneous catalyst for imine synthesis from alcohols and amines through a tandem oxidative process using molecular oxygen as the terminal oxidant.
- Soule, Jean-Francois,Miyamura, Hiroyuki,Kobayashi, Shu
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supporting information
p. 355 - 357
(2013/02/23)
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- General, green, and scalable synthesis of imines from alcohols and amines by a mild and efficient copper-catalyzed aerobic oxidative reaction in open air at room temperature
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A general, green, and scalable synthesis of the useful imines and a,b-unsaturated imines is successfully achieved by a low-loading and powerful, mild and efficient copper-catalyzed aerobic oxidative reaction of alcohols and amines in the open air at room temperature under base- and dehydrating reagent-free conditions. This practical reaction can use air as the economic and green oxidant, tolerates a wide range of substrates, can afford high yields of the target imines on a large scale, and produces water as the only by-product, and thus being the best imination method as yet using alcohols and amines directly.
- Tian, Haiwen,Yu, Xiaochun,Li, Qiang,Wang, Jianxin,Xu, Qing
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supporting information
p. 2671 - 2677,7
(2012/12/12)
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- Synthesis of α, α-dideutero-β-amino esters
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A straight forward entry to α, α-dideutero-β-amino esters starting from the corresponding imines and deuterated acetonitrile has been developed involving a two-step process.
- Chandrasekhar,Pendke, Mrunal,Muththe, Chandrashekar,Akondi, Srirama Murthy,Mainkar, Prathama S.
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experimental part
p. 1292 - 1295
(2012/03/27)
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- Virtual screening and computational optimization for the discovery of covalent prolyl oligopeptidase inhibitors with activity in human cells
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Our docking program, Fitted, implemented in our computational platform, Forecaster, has been modified to carry out automated virtual screening of covalent inhibitors. With this modified version of the program, virtual screening and further docking-based optimization of a selected hit led to the identification of potential covalent reversible inhibitors of prolyl oligopeptidase activity. After visual inspection, a virtual hit molecule together with four analogues were selected for synthesis and made in one-five chemical steps. Biological evaluations on recombinant POP and FAPα enzymes, cell extracts, and living cells demonstrated high potency and selectivity for POP over FAPα and DPPIV. Three compounds even exhibited high nanomolar inhibitory activities in intact living human cells and acceptable metabolic stability. This small set of molecules also demonstrated that covalent binding and/or geometrical constraints to the ligand/protein complex may lead to an increase in bioactivity.
- De Cesco, Stéphane,Deslandes, Sébastien,Therrien, Eric,Levan, David,Cueto, Micka?l,Schmidt, Ralf,Cantin, Louis-David,Mittermaier, Anthony,Juillerat-Jeanneret, Lucienne,Moitessier, Nicolas
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experimental part
p. 6306 - 6315
(2012/09/22)
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- Application of bis(trimethylsilyl) phosphonite in the efficient preparation of new heterocyclic -aminomethyl- H -phosphinic acids
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A simple, reproducible, and efficient preparation of new heterocyclic -aminomethyl-H-phosphinic acids is reported. The synthetic protocol is based on the application of bis(trimethylsilyl) phosphonite, as an efficient phosphorous nucleophile, in the reaction with the corresponding heterocyclic imines. Subsequent methanolysis of the addition intermediates leads to the expected heterocyclic -aminomethyl-H-phosphinic acids in fair to good yields. Additionally, acidic hydrolysis of benzhydrylamino derivatives allows the efficient preparation of free -aminomethyl-H-phosphinic acids in good yields and high purity after simple crystallization. Georg Thieme Verlag Stuttgart New York.
- Olszewski, Tomasz K.,Boduszek, Bogdan
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experimental part
p. 437 - 442
(2011/04/22)
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- A facile, protic ionic liquid route to N-substituted 5-hydroxy-4-methyl-3- oxoisoindoline-1-carboxamides and N-substituted 3-oxoisoindoline-4-carboxylic acids
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Treatment of highly decorated bicyclo[2.2.1]heptadienes with the protic ionic liquid, TfOH:TEA effected quantitative conversion to the corresponding N-substituted 5-hydroxy-4-methyl-3-oxoisoindoline-1-carboxamides. This approach provides rapid access important chemical space for the rapid development of highly functionalised oxoisoindoline and is highly substrate tolerant.
- Gordon, Christopher P,Byrne, Nolene,McCluskey, Adam
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experimental part
p. 1000 - 1006
(2010/10/18)
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- Structural-activity relationship study of highly-functionalized imidazolines as potent inhibitors of nuclear transcription factor-κB mediated IL-6 production
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We herein describe the synthesis and anti-inflammatory properties of a small library of imidazoline-based NF-κB inhibitors. The structure-activity relationship of various substituents on an imidazoline core structure was evaluated for the ability to inhibit NF-κB mediated IL-6 production. Optimization of the scaffolds was pursued by correlating luciferase-based NF-κB reporter assays with inhibition of IL-6 production in IL-1β stimulated human blood. Several derivatives were found to inhibit NF-κB mediated IL-6 production in the nanomolar range in IL-1β stimulated human blood.
- Kahlon, Daljinder K.,Lansdell, Theresa A.,Fisk, Jason S.,Tepe, Jetze J.
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experimental part
p. 3093 - 3103
(2009/10/02)
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- Convenient synthesis of pyrrolidines by amphiphilic allylation of imines with 2-methylenepropane-1,3-diols
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(Chemical Equation Presented). A straightforward route: The combination of a palladium catalyst and triethylborane promotes the amphiphilic (nucleophilic-electrophilic) allylation of aldimines, prepared in situ from a wide variety of aromatic and aliphatic aldehydes and amines, with commercially available 2-methylenepropane-1,3-diols to provide pyrrolidines (see scheme).
- Kimura, Masanari,Tamaki, Takato,Nakata, Masanori,Tohyama, Katsumi,Tamaru, Yoshinao
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supporting information; experimental part
p. 5803 - 5805
(2009/03/11)
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- Synthesis of advanced intermediates of lennoxamine analogues
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A simple and convenient method for synthesis of advanced isoindolone intermediates of lennoxamine and analogues is described in this paper. The intramolecular Diels-Alder reaction of furan is used as a key step in this synthesis. Georg Thieme Verlag Stuttgart.
- Sarang, Prajakta S.,Yadav, Arun A.,Patil, Prashant S.,Krishna, Urlam Murali,Trivedi, Girish K.,Salunkhe, Manikrao M.
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p. 1091 - 1095
(2008/02/02)
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- α-Acylaminophosphonates possessing epoxyisoindolone moiety
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α-Acylaminophosphonates possessing an epoxyisoindolone moiety were prepared with good stereoselectivity (de≥80%) by?a tandem acylation/[4+2]-cycloaddition reaction between maleic anhydride and α-aminophosphonates derived from a furfurylamine. The cycloaddition products have an opposite orientation of epoxy and phosphonate groups, which was confirmed by NMR spectroscopy and X-ray crystal structure analysis.
- Kachkovskyi, Georgiy O.,Kolodiazhnyi, Oleg I.
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p. 12576 - 12582
(2008/03/14)
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- Eco-friendly synthesis of imines by ultrasound irradiation
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A series of imines was synthesized by an ultrasound-assisted reaction of aldehydes and primary amines using silica as the promoter. Products were obtained in high yields even in large scale synthesis.
- Guzen, Karla P.,Guarezemini, Alexandre S.,órf?o, Aline T.G.,Cella, Rodrigo,Pereira, Claudio M.P.,Stefani, Hélio A.
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p. 1845 - 1848
(2008/02/05)
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- General and environmentally friendly synthesis of heterocyclic multidentate molecules based on microwave-assisted heating protocol
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An efficient microwave heating methodology for the synthesis of heterocyclic multidentate molecules is reported. Each compound was obtained with high yield and purity in a few minutes from easily available starting materials such as amines, heteroaldehydes and N-hydroxymethyl pyrazoles or triazoles. In addition, this approach allows synthesis without any solvent or organic and inorganic by-products.
- Regnier, Thomas,Lavastre, Olivier
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p. 155 - 159
(2007/10/03)
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- One-pot synthesis of N-chloroacetyl 1-aminoalkyl phosphonates - Precursors of 4-phosphono-β-lactams
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4-Phosphono-β-lactams are synthesized via a three-step sequence, including final formation of the C3-C4 bond through a phosphorus-stabilized carbanion. The chlorinated precursors can be synthesized via two different methods: a one-pot N-acylation of an aromatic imine followed by addition of a trialkyl phosphite or phosphonylation of a suitable imine followed by N-acylation in a separate reaction step. The former method was preferred because of the ease of the reaction and the good yields obtained. Georg Thieme Verlag Stuttgart.
- Moonen, Kristof,Stevens, Christian V.
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p. 3603 - 3612
(2007/10/03)
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- An efficient approach to isoindolo[2,1-b][2]benzazepines via intramolecular [4+2] cycloaddition of maleic anhydride to 4-α-furyl-4-N-benzylaminobut- 1-enes
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Acylation of 4-α-furyl-4-N-benzylaminobut-1-enes with maleic anhydride gave 4-oxo-3-aza-10-oxatricyclo[5.2.1.01,5]dec-8-ene-6- carboxylic acid via amide formation followed by intramolecular Diels-Alder reaction of furan (IMDAF). The cycloaddition proceeded under mild reaction conditions (25°C) and provided only the exo-adduct in quantitative yield. Treatment of this compound with PPA gave isoindolo[2,1-b][2]benzazepine derivatives via ring opening, aromatization and intramolecular electrophilic alkylation. In order to extend the scope of the reaction sequence, 7-oxo-5,11b,12,13-tetrahydro-7H-isoindolo[2,1-b][2]benzazepine-8-carboxylic acids were further transformed into useful synthetic intermediates. Graphical Abstract.
- Zubkov, Fedor I.,Boltukhina, Ekaterina V.,Turchin, Konstantin F.,Varlamov, Alexey V.
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p. 8455 - 8463
(2007/10/03)
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- Thiourea-Catalyzed Enantioselective Hydrophosphonylation of Imines: Practical Access to Enantiomerically Enriched α-Amino Phosphonic Acids
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Chiral thiourea 1b catalyzes the highly enantioselective hydrophosphonylation of a wide range of N-benzyl imines. The hydrophosphonylation products are readily deprotected by hydrogenolysis, providing access to free α-amino phosphonic acids in highly enantioenriched form. Copyright
- Joly, Guy D.,Jacobsen, Eric N.
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p. 4102 - 4103
(2007/10/03)
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- Synthesis of 4-phosphono-β-lactams via phosphite addition to acyliminium salts
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4-Aryl-4-phosphono-β-lactams are prepared by acylation of iminium salts with chloroacetyl chloride followed by phosphite addition and ring closure using sodium hydride as a base. Deacylation of the iminium salt is in competition with the desired addition of phosphites to acyliminium salts, which lowers the yield of the reaction.
- Stevens, Christian V.,Vekemans, Wannes,Moonen, Kristof,Rammeloo, Thomas
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p. 1619 - 1622
(2007/10/03)
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- An improved and stereoselective route to all-cis-2,6-disubstituted 4-hydroxypiperidines from accessible 4-substituted 4-N-benzylaminobut-1-enes
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The reaction between allylmagnesium bromide and imines 5a-l leads to the corresponding 4-substituted 4-N-benzylaminobut-1-enes 6a-1, which were oxidized in a regioselective manner to the alkenylnitrones 7a-l. The intramolecular 1,3-dipolar cycloaddition of these nitrones gave 2-spiroannulated or 2-substituted 6-exo-phenyl-1-aza-7-oxabicyclo[2.2.1]heptanes 8a-j. Reductive cleavage of the N-O bond of the obtained bicycles afforded the diverse substituted 4-hydroxypiperidines 9a-h in good yields. This stereoselective approach allowed the preparation of all-cis-4-hydroxy-6-phenyl-2-nonylpiperidine (9i), a close analogue of dendrobatid frog alkaloid 241D.
- Varlamov, Alexey,Kouznetsov, Vladimir,Zubkov, Fedor,Chernyshev, Alexey,Shurupova, Olga,Vargas Mendez, Leonor Y.,Palma Rodriguez, Alirio,Rivero Castro, Juliette,Rosas-Romero, Alfredo J.
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p. 771 - 783
(2007/10/03)
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- Synthesis of imines, diimines and macrocyclic diimines as possible ligands, in aqueous solution
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Although it is recognized that the presence of water is disadvantageous for imine synthesis, we demonstrate that such synthesis can be effective in completely aqueous media, without any catalyst and under mild conditions. Thus, arylaryl, aryl-alkyl, alkyl-aryl and alkyl-alkyl monoimines as well as a large variety of diimines are obtained by direct condensation of the corresponding carbonyl compounds and amines, in water. The same process is used to synthesize macrocyclic diimines starting from methylene, ethylene, trimethylene and tetramethylene glycol bis(2-formylphenyl ether) and ethylene-, trimethylene- and tetramethylene-diamine, some of these macrocycles being known for their chelating properties.
- Simion, Alina,Simion, Cristian,Kanda, Tadeshige,Nagashima, Satoko,Mitoma, Yoshiharu,Yamada, Tomoko,Mimura, Keisuke,Tashiro, Masashi
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p. 2071 - 2078
(2007/10/03)
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- Intra-molecular Diels-Alder reactions of citraconamic acids from furfurylamines and citraconic anhydride: Effects of substitution in the furan ring on regioselectivity
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Regioselectivity in the intra-molecular Diels-Alder (IMDA) reaction of furfurylcitraconamic acids derived from N-benzylfurfurylamines and citraconic anhydride can be controlled by substituents located in the furan ring and by reaction conditions. Reactions conducted under kinetic conditions resulted in cycloaddition products having methyl and aminomethylene substituent in 1,3-relationship whereas under thermodynamic conditions, excepting in the case of the 3-methylsulfanyl group, the products rearranged to more stable cycloadducts in which the substituents are in 1,2-relationship. Product formation can be explained on the basis of frontier orbital interactions and steric considerations.
- Murali, Rajappa,Surya Prakash Rao,Scheeren, Hans W
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p. 3165 - 3174
(2007/10/03)
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- Antimalarial t-butylperoxyamines
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Twelve t-butylperoxyamines (6-17) were synthesized as targeted antimalarials and evaluated for antimalarial activity in vivo against Plasmodium berghei in mice and in vitro against both chloroquine sensitive and chloroquine resistant strains of Plasmodium falciparum. Compound 8 was found to have highest potency with activity at 80 and 160 mg/kg dose in vivo and compound 11 exhibited highest efficacy in vitro.
- Sundar,Jacob,Bhat, Sujata V,Valecha, Neena,Biswas, Sukla
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p. 2269 - 2272
(2007/10/03)
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- Diazoketones as precursors in β-lactam synthesis. New insights into the mechanism of the photochemically induced Staudinger reaction
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Diazoketones 1-3, derived from suitably protected amino acids (Ala, Val and Tle), have been photochemically rearranged in the presence of imines leading exclusively to trans-arranged 4-aryl- and cinnamoyl-substituted β-lactams 17-33 with up to 84% yield. Selectivities were dependent on the steric demand of the amino acid side-chain ranging from 65:35 to 90:10. The relative configurations were proved by several X-ray crystal structures and comparison of NMR spectra. Further reactions of the azetidinones at position C-4 have been performed: electron-rich aryl substituents (e.g., 4-methoxyphenyl, furyl and thienyl) could be degraded to carboxylic acids 34 and 35 which were further transformed to acetoxy derivatives (compounds 36 and 37) in a Kolbe reaction of type II. The cinnamoyl group could be oxidized to the formyl group by ozonolysis (→38,39). The mechanism of the photochemically induced β-lactam formation is discussed in detail.
- Linder,Frey,Podlech
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p. 2566 - 2577
(2007/10/03)
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- Synthesis and biological activity of heterocyclic aminophosphonates
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A variety of synthetic methods for preparation of heterocyclic aminophosphonates is presented; which are concerning furyl, thienyl, pyrryl and pyridyl derivatives of aminomethanephosphonic acid and also phosphonic analogues of proline and homoproline. The obtained heterocyclic aminophosphonates were used as starting materials for synthesis of some peptidyl phosphonates. The compounds were evaluated as inhibitors of serine proteases. Most of the obtained heterocyclic aminophosphonates were preliminary tested as potential herbicides against selected plants, and some of them showed the herbicidal activity.
- Boduszek, Bogdan
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p. 433 - 436
(2007/10/03)
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- 1-aminophosphonic acids and esters bearing heterocyclic moiety. Part 2. 1 pyridine, pyrrole and emidazole derivatives
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The benzylic amines (benzylamine, benzhydrylamine and benzyl carbamate) were applied in the synthesis of aminophosphonates derived from pyridine, pyrrole and imidazole. The Schiff bases obtained from corresponding heterocyclic aldehydes and benzylic amines were caused to react with diphenyl phosphorate or dibenzyl phosphonate to form corresponding heterocyclic aminophosphonates in good yields. The N-(benzylamino)-phosphonates were deblocked by catalytic hydrogenolysis. The benzhydryl group from the phosphonates was removed by acidic hydrolysis, and the carbobenzyloxy group from the phosphonates can be easy removed by treatment with a solution of 30% HBr in acetic acid, as well. It was found that during acidic hydrolysis of 2-and 4-pyridylmethylaminophosphonates a rearrangement occurred, combined with a cleavage of C-P bond in the phosphonate molecules and subsequent formation of the corresponding amines.
- Boduszek, Bogdan
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p. 209 - 218
(2007/10/03)
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- AN EFFICIENT SYNTHESIS OF 1-AMINOPHOSPHONIC ACIDS AND ESTERS BEARING HETEROCYCLIC MOIETY
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New α-aminophosphonic esters and acids derived from furan, thiophene and pyrazole were prepared in high yield, in the reactions of benzylamine, benzhydrylamine or benzyl carbamate with heterocyclic aldehydes and diethyl or diphenyl phosphonates.The protecting groups at amine (benzyl or benzhydryl) were removed by hydrogenolysis or hydrolysis, respectively.The N-benzoyloxycarbonyl (Z-group) was removed by treatment with 45percent HBr in acetic acid. Key words: Diphenyl α-aminofurylmethyl phosphonate, α-aminothienylmethylphosphonic acid, α-aminopyrazolylmethylphosphonic acid, imines, benzyl carbamate.
- Boduszek, Bogdan
-
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- A simple, convenient and general method for the synthesis of N-acylalkylaminomethyl- and N-acylalkylamino(alkyl, aryl, heteroaryl)methylphosphonates and -phosphine oxides
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A variety of N-acylalkylaminomethyl- and alkylamino(alkyl, aryl, heteroaryl)methylphosphonates and -phosphine oxides has been efficiently prepared by acylation of suitable Schiff bases and subsequent treatment of the chloromethylcarboxamide intermediates with the appropriate phosphorylating agent.
- Couture,Deniau,Grandclaudon
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p. 953 - 956
(2007/10/02)
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- Synthesis of β-lactams by condensation of titanium enolates of 2-pyridylthioesters with imines. Influence of the imine structure on the trans/cis stereoselectivity
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The condensation of the titanium enolates of C-2 alkyl substituted 2-pyridylthioesters with imines affords β-lactams in trans/cis ratios that largely depend on the structure of the C-imine residue. Bulky and non-chelating heteroatom-containing groups lead to the formation of trans β-lactams, while sterically non-requiring or chelating groups favour the formation of the cis-products. On the basis of NMR evidences a rationale is proposed to account for the observed stereoselectivity.
- Annunziata, Rita,Benaglia, Maurizio,Cinquini, Mauro,Cozzi, Franco,Ponzini, Francesco,Raimondi, Laura
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p. 2939 - 2948
(2007/10/02)
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- PHOTO-OXIDATIVE CLEAVAGE OF A FURAN-AZETIDINONE CARBON-CARBON BOND: A SYNTHESIS OF 4-ACETOXYAZETIDINONE
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A stereoselective synthesis of the 4-acetoxyazetidinione (1) from methyl 3(R)-hydroxybutyrate is reported.The synthesis involved stereoselective preparation of a 4-(2-furanyl)azetidinone that was allowed to react with singlet oxygen.The resulting endoperoxide intermediates underwent direct rearrangement to an acyloxyazetidinone that on reaction with sodium acetate gave 1 in modest yield.An improved yield of 1 was obtained by treatment of the endoperoxides with hydrogen peroxide followed by acetic anhydride to give an α-alkoxy acylperoxide that underwent thermal rearrangement to 1.
- Lynch, Joseph E.,Laswell, William L.,Volante, Ralph P.,Reamer, Robert A.,Tschaen, David M.,Shinkai, Ichiro
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p. 1029 - 1037
(2007/10/02)
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