- Concise synthesis of multisubstituted isoquinolines from pyridines by regioselective diels-alder reactions of 2-silyl-3,4-pyridynes
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A four-step regioselective synthesis of multisubsti-tuted isoquinoline derivatives from 3-bromopyridines was developed by the Diels-Alder (DA) reactions of 2-silyl-3,4-pyridynes with furans, followed by functional-group transformations. In particular, the silyl group at the C2-position of the 3,4-pyridynes played two important roles: firstly, it functioned as the directing group for the DA reaction, and secondly, it served to introduce diverse substituents at the C1-position of the isoquinolines by electrophilic ipso-substitution.
- Ikawa, Takashi,Urata, Hirohito,Fukumoto, Yutaka,Sumii, Yuta,Nishiyama, Tsuyoshi,Akai, Shuji
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Read Online
- Synthesis of Indole- and Pyrrole-Fused Seven-Membered Nitrogen Heterocycles via Acid-Base Switchable Cyclization Involving Cleavage of Amide C?N Bonds
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We report the method for synthesis of indole- and pyrrole-fused seven-membered nitrogen heterocycles by means of acid-base switchable cyclization reactions. The reactions involved cleavage of amide C?N bonds, chemoselective N-1 or C-3 acylation, and 1,4-M
- Hao, Yanke,Zhou, Pan,Niu, Kaikai,Song, Hongjian,Liu, Yuxiu,Zhang, Jingjing,Wang, Qingmin
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supporting information
p. 281 - 285
(2021/11/09)
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- Addition of Chloroprene Grignards to Aromatic Aldehydes: Synthesis of Homoallenyl Alcohols
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A general procedure for the one-pot synthesis of racemic homoallenyl alcohols from the corresponding aldehyde and chloroprene-derived Grignards is described. Employing bis[2-dimethylaminoethyl]ether (BDMAEE) as an additive at low temperatures shifts the selectivity of the chloroprene Grignard addition to aldehydes such that it is almost exclusive toward allene formation. In a set of follow-up experiments, simple and more elaborate methods for further derivatization have been demonstrated, allowing quick access to more complex structures.
- Geissler, Arne G. A.,Breit, Bernhard
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supporting information
p. 2621 - 2625
(2021/04/12)
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- Ru-Catalyzed Carbonylative Murai Reaction: Directed C3-Acylation of Biomass-Derived 2-Formyl Heteroaromatics
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The Murai reaction is a ruthenium-catalyzed transformation leading to alkylated arenes through the C?C bond formation between an alkene and an arene bearing a directing group. Discovered in the nineties, this useful C?H activation based coupling has been the object of intense study since its discovery. After having studied the Murai reaction on 2-formylfurans of biomass derivation, we describe here the carbonylative version applied to 2-formylfurans, 2-formylpyrrols and 2-formylthiophenes. This acylation reaction takes place regioselectively at C3 position of the heterocyclopentadienes thanks to the installation of removable imine directing groups. The transformation can be achieved by treating the two reaction partners with a catalytic amount of Ru3(CO)12, in toluene at 120–150 °C, after CO bubbling, at atmospheric pressure. DFT computations of the full catalytic cycle help in deciphering the mechanism of this transformation, and to rationalize the different behaviors depending on the nature of imine directing groups. (Figure presented.).
- Sala, Roberto,Roudesly, Fares,Veiros, Luis F.,Broggini, Gianluigi,Oble, Julie,Poli, Giovanni
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supporting information
p. 2486 - 2493
(2020/05/06)
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- Serendipitous base catalysed condensation-heteroannulation of iminoesters: a regioselective route to the synthesis of 4,6-disubstituted 5-azaindoles
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A serendipitous discovery of a novel one-pot synthesis of 4,6-disubstituted 5-azaindoles is reported herein. In the presence of Hunig's base, various N-substituted pyrrole-2-carboxaldehydes have been efficiently transformed into their corresponding 4,6-disubstituted 5-azaindoles through an imine mediated cascade condensation-heteroannulation. The synthetic value of the methodology is established by preparing a novel chemical analogue of a cannabinoid receptor type 2 (CB2) agonist.
- Chelvam, Venkatesh,Dudhe, Premansh,Pathak, Biswarup,Venkatasubbaiah, Krishnan
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supporting information
p. 1582 - 1587
(2020/03/06)
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- Design, Synthesis, and Conformational Analysis of Oligobenzanilides as Multifacial α-Helix Mimetics
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The design, synthesis, and conformational analysis of an oligobenzanilide helix mimetic scaffold capable of simultaneous mimicry of two faces of an α-helix is reported. The synthetic methodology provides access to diverse monomer building blocks amenable to solid-phase assembly in just four synthetic steps. The conformational flexibility of model dimers was investigated using a combination of solid and solution state methodologies supplemented with DFT calculations. The lack of noncovalent constraints allows for significant conformational plasticity in the scaffold, thus permitting it to successfully mimic residues i, i+2, i+4, i+6, i+7, and i+9 of a canonical α-helix.
- Flack, Theo,Romain, Charles,White, Andrew J. P.,Haycock, Peter R.,Barnard, Anna
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supporting information
p. 4433 - 4438
(2019/06/27)
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- Design of fluorescent probes with optimized responsiveness and selectivity to GSH
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We designed and synthesized a series of BODIPY based probes with fast and distinct ratiometric responsiveness for discriminative detection of GSH from Cys and Hcy. The discriminative detection is based on the different products obtained by the SNAr between probes and thiol-containing amino acids. The amino group of the obtained thioether from the reaction with Cys or Hcy but not GSH would trigger an intramolecular nucleophilic substitution through five- or six-membered cyclic transition state, finally yielding an amino substituted derivative. To achieve highly discriminative detection and fast response, a series of structure modifications and improvements have been made by elongating the π-conjugation and introducing electron withdrawing groups, finally affording probe BOD-DBNPF with optimized responsiveness and selectivity. Importantly, BOD-DBNPF was successfully used for the selective detection of GSH from Cys with distinct fluorescent ratiometric responses in living HeLa cells.
- Chen, Ji-An,Zhang, Zhen-Yu,Gao, Jie,Tan, Jia-Hui,Gu, Xian-Feng
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supporting information
p. 1226 - 1230
(2019/03/27)
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- ANTIVIRAL COMPOUNDS AND USE THEREOF
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The present invention relates to compounds of formula (I), their use as medicaments, in particular as broad spectrum antiviral agents, their combination with a further antiviral agent and relative pharmaceutical compositions. In particular, the compounds of the invention are useful in the treatment of a disease caused by an enveloped virus.
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Page/Page column 34
(2019/10/04)
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- Benzonorbornadiene Derivatives and Reactions Thereof
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A bioorthogonal molecule can include a molecule having a structure according the above wherein R1-R8 are independently selected from H, a substituted or unsubstituted C1-C4 alkyl or alkylene group, COOH, COORsu
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Paragraph 0309-0310
(2019/10/17)
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- AMINOTRIAZOLE IMMUNOMODULATORS FOR TREATING AUTOIMMUNE DISEASES
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1-Acyl-3-(heteroaryl)-1H-1,2,4-triazol-5-amines of formula (I) are disclosed. These compounds inhibit Coagulation Factor XIIa in the presence of thrombin and other coagulation factors. They are useful to treat autoimmune diseases.
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Paragraph 084
(2017/08/07)
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- AMINOACYLINDAZOLE IMMUNOMODULATORS FOR TREATMENT OF AUTOIMMUNE DISEASES
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2-Acylindazole compounds of formula I or formula II are disclosed. These compounds inhibit Coagulation Factor XIIa. They are useful to treat autoimmune diseases.
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Paragraph 380
(2017/12/29)
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- Rapid and efficient tetrazine-induced drug release from highly stable benzonorbornadiene derivatives
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A novel class of bioorthogonal release reactions based on benzonorbornadiene derivatives was developed. These carrier molecules are highly stable at physiological conditions, but react rapidly with 1,2,4,5-tetrazines, and near-quantitatively release cargo
- Xu, Minghao,Tu, Julian,Franzini, Raphael M.
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supporting information
p. 6271 - 6274
(2017/07/10)
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- Palladium-catalyzed regioselective allylation of five-membered heteroarenes with allyltributylstannane
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Palladium-catalyzed allylation reactions of 2-(chloromethyl)thiophenes, 2-(chloromethyl)furans, and N-protected 2-(chloromethyl)-1H-pyrroles with allyltributylstannane were described in this study. This type of allylation reaction regioselectively occurred on the heteroarene rings to produce allylated dearomatization products or allylated heteroarenes with satisfactory yields.
- Zhang, Sheng,Yu, Xiaoqiang,Feng, Xiujuan,Yamamoto, Yoshinori,Bao, Ming
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supporting information
p. 3842 - 3845
(2015/03/30)
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- Synthesis, structures and reactivity of 2-phosphorylmethyl-1H-pyrrolato complexes of titanium, yttrium and zinc
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The reaction of secondary phosphines HPR2 (R = Ph, Cy) with pyrrole-2-aldehydes gives a new family of 2-phosphorylmethyl-1H-pyrroles as potentially chelating mono-anionic ligands. The reaction with Ti(NMe 2)4 affords octahedral Ti(NMe2) 2{NC4H2(4-R′)CH2P(O)R 2}2 (R′ = H, But). While the diphenylphosphoryl complexes adopt a configuration with trans-pyrrolato ligands, the dicyclohexyl analogue prefers an all-cis conformation, with profound consequences on metal-ligand bonding. The reaction of sterically undemanding HNC4H3CH2P(O)Ph2 with Y[N(SiHMe 2)2]3(THF)2 give the homoleptic complex Y[NC4H3CH2P(O)Ph2] 3; mixed-ligand intermediates Y[N(SiHMe2) 2]2(N-O) and Y[N(SiHMe2)2](N-O) 2 were identifiable but could not be isolated. The bulky ligand HNC4H2(5-But)CH2P(O)Ph2 does not react with Ti(NMe2)4 but protolyses Zn[N(SiMe3)2]2 to give a 1: 2 complex Zn(N-O)2 as the only isolable product. On the other hand, its reaction with Y[N(SiHMe2)2]3(THF)2 affords the mono-amido complex Y{N(SiHMe2)2}{NC 4H3(5-But)CH2P(O)Ph 2}2 which shows good activity for the ring-opening polymerisation of cyclic esters. The Royal Society of Chemistry 2009.
- Broomfield, Lewis M.,Wright, Joseph A.,Bochmann, Manfred
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experimental part
p. 8269 - 8279
(2010/03/04)
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- BCRP/ABCG2 INHIBITOR
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The present invention is directed to a breast cancer resistance protein (BCRP/ABCG2) inhibitor. The BCRP inhibitor contains, as an active ingredient, an acrylonitrile derivative represented by formula (1): wherein one of R1 and R2 re
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Page/Page column 20
(2008/06/13)
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- 4-PHENYL-5-OXO-1,4,5,6,7,8-HEXAHYDROQUINOLINE DERIVATIVES THE TREATMENT OF INFERTILITY
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The present invention relates to 4-phenyl-5-oxo-l,4)5,6,7,8-hexahydroquinoline derivatives according to Formula I, Formula I or a pharmaceutically acceptable salt thereof, wherein R1 is (l-6C)alkyl, (2-6C)alkenyl or (2-6C)aDcynyl; R2, R3 are independently halogen, (l-4C)allcyl, (2-4C)alkenyl, (2-4C)- alkynyl, (1 -4C)aBcoxy, (3-4C)alkenyloxy or (3-4C)alkynyloxy; R4 is phenyl or (2-5C)- heteroaryl, both substituted with R7 and optionally substituted on the (hetero)aromatic ring with one or more substituents selected from hydroxy, amino, halogen, nitro, trifluoromethyl, cyano, (l-4C)alkyl, (l-4C)alkoxy , (l-4C)alkylthio and (di)(l-4C)- alkylamino. The invention also relates to pharmaceutical compositions comprising said derivatives, as well as to the use of these 4-phenyl-5-oxo-l, 4,5,6, 7,8-hexahydro- quinoline derivatives in therapy, more specifically for the treatment of infertility
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Page/Page column 63
(2010/11/24)
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- Hydrazines and azides via the metal-catalyzed hydrohydrazination and hydroazidation of olefins
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The discovery, study, and implementation of the Co- and Mn-catalyzed hydrohydrazination and hydroazidation reactions of olefins are reported. These reactions are equivalent to direct hydroaminations of C-C double bonds with protected hydrazines or hydrazoic acid but are based on a different concept in which the H and the N atoms come from two different reagents, a silane and an oxidizing nitrogen source (azodicarboxylate or sulfonyl azide). The hydrohydrazination reaction using di-tert-butyl azodicarboxylate is characterized by its ease of use, large functional group tolerance, and broad scope, including mono-, di-, tri-, and tetrasubstituted olefins. Key to the development of the hydroazidation reaction was the use of sulfonyl azides as nitrogen sources and the activating effect of tert-butyl hydroperoxide. The reaction was found to be efficient for the functionalization of mono-, di-, and trisubstituted olefins, and only a few functional groups are not tolerated. The alkyl azides obtained are versatile intermediates and can be transformed to the free amines or triazoles without isolation of the azides. Preliminary mechanistic investigations suggest a rate-limiting hydrocobaltation of the alkene, followed by an amination reaction. Radical intermediates cannot be ruled out and may be involved.
- Waser, Jerome,Gaspar, Boris,Nambu, Hisanori,Carreira, Erick M.
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p. 11693 - 11712
(2007/10/03)
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- INHIBITORS OF DIPEPTIDYLPEPTIDASE IV
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The present invention relates to inhibitors of post-proline cleaving enzymes, such as inhibitors of dipeptidyl peptidase IV, as well as pharmaceutical compositions thereof, and methods of using such inhibitors. In particular, the inhibitors of the present invention are improved over those in the prior art by selection of particular classes of sidechains in the P1 and/or P2 position of the inhibitor that contain a carboxylic acid moiety. The compounds of the present invention can have a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.
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Page/Page column 69
(2008/06/13)
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- Synthesis and properties of ring-deactivated deuterated (hydroxymethyl)pyrroles
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A sequence, based on a Mitsunobu displacement at the hydroxymethyl position of deuterium-labeled, N-substituted 2-(hydroxymethyl)pyrroles, is reported as a general procedure to determine the ability of the N-substituent to deactivate the heterocycle. An S
- Abell, Andrew D.,Nabbs, Brent K.,Battersby, Alan R.
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p. 1741 - 1746
(2007/10/03)
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- Imidazole, Triazole and tetrazole derivatives
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Imidazole, triazole and tetrazole derivatives of formula (I) are selective agonists of 5-HT1 -like receptors and are therefore useful in the treatment of clinical conditions, in particular migraine and associated disorders, for which a selective agonist of these receptors is indicated, wherein the broken circle represents two non-adjacent double bonds in any position in the five-membered ring; two, three or four of V, W, X, Y and Z represent nitrogen and the remainder represent carbon provided that, when two of V, W, X, Y and Z represent nitrogen and the remainder represent carbon, then the said nitrogen atoms are in non-adjacent positions within the five-membered ring; E represents a bond or a straight or branched alkylene chain containing from 1 to 4 carbon atoms; F represents a group of formula (a); U represents nitrogen or C--R2 ; B represents oxygen, sulphur or N--R3 ; R1 represents a group of formula (i), (ii) or (iii).
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- Divergent pathways in the intramolecular reactions between rhodium-stabilized vinylcarbenoids and pyrroles: Construction of fused tropanes and 7-azabicyclo[4.2.0]octadienes
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The rhodium(II)-catalyzed intramolecular reaction between vinyldiazomethanes and pyrroles leads to a novel synthesis of fused tropanes. The reaction occurs by a stepwse 3 + 4 annulation mechanism between a rhodium-stabilized vinylcarbenoid intermediate and the pyrrole rather than by the typical tandem cyclopropanation/Cope rearrangement sequence. The outcome of the reaction is very sensitive to the vinylcarbenoid structure. In particular, the presence of a 2-siloxy substituent on the vinylcarbenoid strongly favors the formation of fused tropanes. In the absence of such functionality, the formation of fused 7-azabicyclo[4.2.0]octadienes becomes the dominant reaction pathway.
- Davies, Huw M. L.,Matasi, Julius J.,Ahmed, Gulzar
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p. 2305 - 2313
(2007/10/03)
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- Synthesis of N-protected 2-hydroxymethylpyrroles and transformation into acyclic oligomers
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The synthesis of N-tosylated and N-Boc-protected 2-hydroxymethyl-pyrroles 2a-c and 3a-d and their transformation into di- and tripyrroles 18, 20a and 20b as well as the preparation of the vinyl- and ethynylpyrroles 13a, 13b and 15 is described. The pyrrole-2-carboxylic acid ethyl esters 7a and b and the pyrrole-2-carbaldehydes 4a-d were transformed into their N-protected derivatives 5a, 5b, 6a-d, 8a and 8b in 69-97% yield and reduced to give the corresponding hydroxymethylpyrroles 2a-c and 3a-d in 79-96% yield; treatment of 2b with 17, 19a and 19b in 0.5% hydrochloric acid gives the dipyrrole 18 and the tripyrroles 20a and 20b in 20-28% yield.
- Tietze, Lutz F.,Kettschau, Georg,Heitmann, Katja
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p. 851 - 857
(2007/10/03)
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- Synthesis of enantiomerically pure D- and L-(heteroaryl)alanines by asymmetric hydrogenation of (Z)-α-amino-α,β-didehydro esters
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Homogeneous asymmetric hydrogenation of a wide range of methyl and tert-butyl (Z)-2-(acylamino)-3-(heteroaryl)acrylates (see 1a-f and 2a-d, f, g, resp.) catalyzed by diphosphinerhodium catalysts was studied for the synthesis of enantiomerically pure 3-fur
- Masquelin,Broger,Muller,Schmid,Obrecht
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p. 1395 - 1411
(2007/10/02)
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