- Synthesis and biological evaluation of boron-containing polyamines as potential agents for neutron capture therapy of brain tumors
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New boron-containing spermidine/spermine (SPD/SPM) analogues have been synthesized: N5-[4-(2-aminoethyl-o-carboranyl)butyl] and N5-{4-[(2,3- dihydroxypropyl)-o-carboranyl]butyl} SPD/SPM derivatives (ASPD-5, ASPM-5, DHSPD-5, and DHSPM
- Zhuo, Jin-Cong,Cai, Jianping,Soloway, Albert H.,Barth, Rolf F.,Adams, Dianne M.,Ji, Weihua,Tjarks, Werner
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Read Online
- Diastereoselective syntheses of substituted cis-hydrindanones featuring sequential inter- and intramolecular Michael reactions
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The hydrindane (bicyclo[4.3.0]nonane) structural motif (1) and related cis-1-hydrindanone skeleton (2) are common substructures in many natural products. Herein, we describe efficient access to substituted cis-1-hydrindanones enabled by a sequence of Mich
- Liu, Junjia,Marsini, Maurice A.,Bedell, T. Aaron,Reider, Paul J.,Sorensen, Erik J.
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Read Online
- Radical Carbonyl Propargylation by Dual Catalysis
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Carbonyl propargylation has been established as a valuable tool in the realm of carbon–carbon bond forming reactions. The 1,3-enyne moiety has been recognized as an alternative pronucleophile in the above transformation through an ionic mechanism. Herein, we report for the first time, the radical carbonyl propargylation through dual chromium/photoredox catalysis. A library of valuable homopropargylic alcohols bearing all-carbon quaternary centers could be obtained by a catalytic radical three-component coupling of 1,3-enynes, aldehydes and suitable radical precursors (41 examples). This redox-neutral multi-component reaction occurs under very mild conditions and shows high functional group tolerance. Remarkably, bench-stable, non-toxic, and inexpensive CrCl3 could be employed as a chromium source. Preliminary mechanistic investigations suggest a radical-polar crossover mechanism, which offers a complementary and novel approach towards the preparation of valuable synthetic architectures from simple chemicals.
- Huang, Huan-Ming,Bellotti, Peter,Daniliuc, Constantin G.,Glorius, Frank
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supporting information
p. 2464 - 2471
(2020/12/07)
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- 6,7-DIHYDRO-5H-PYRIDO[2,3-C]PYRIDAZINE DERIVATIVES AND RELATED COMPOUNDS AS BCL-XL PROTEIN INHIBITORS AND PRO-APOPTOTIC AGENTS FOR TREATING CANCER
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The present invention discloses 6,7-dihydro-5H-pyrido[2,3- c]pyridazine, 1,2,3,4-tetrahydroquinoline, 1H-indole, 3,4- dihydro-2H-1,4-benzoxazine, 1H-pyrrolo[2,3-b]pyridin-1-yl, 7H- pyrrolo[2,3-c]pyridazine, 5H,6H,7H,8H,9H-pyridazino[3,4-b]azepine derivatives and related compounds of formula (I) as Bcl-xL protein inhibitors for use as pro-apoptotic agents for treating cancer, autoimmune diseases or immune system diseases. Formula (I). The description discloses the preparation of exemplary compounds (e.g. pages 113 to 354 examples 1 to 221) as well as pharmacological studies with relevant data (e.g. pages 355 to 367; examples A to E; tables 1 to 5). Exemplary compounds are e.g. 2-{6-[(1,3-benzothiazol-2-yl) amino]-1,2,3,4-tetrahydroquinolin-1-yl}-1,3-thiazole-4-carboxylic acid (example 1) or e.g. 3-{1-[(adamantan-1-yl)methyl]-5- methyl-1H-pyrazol-4-yl}-6-{3-[(1,3-benzothiazol-2-yl)amino]-4- methyl-5H,6H,7H,8H-pyrido[2,3-c]pyridazin-8-yl]pyridine-2-carboxylic acid (example 24).
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Page/Page column 170
(2021/02/05)
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- CARBOXY DERIVATIVES WITH ANTIINFLAMMATORY PROPERTIES
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The invention relates to compounds of formula (I) and to their use in treating or preventing an inflammatory disease or a disease associated with an undesirable immune response: (I) wherein, RA1, RA2, RC and RD are as defined herein.
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Page/Page column 114; 115
(2021/07/02)
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- Diethylzinc-Mediated Radical 1,2-Addition of Alkenes and Alkynes
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A novel diethylzinc-mediated radical 1,2-addition of perfluoroalkyl iodides to unactivated alkenes and alkynes is presented, which demonstrates a novel way to generate an ethyl difluoroacetate radical. This method is highly efficient and gives full conversions of the substrates, high yields of the products, and negligible byproducts and requires no column chromatography purifications. The mild conditions enable this protocol to exhibit excellent functional group compatibility.
- Li, Xin,He, Songtao,Song, Qiuling
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supporting information
p. 2994 - 2999
(2021/05/04)
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- Zirconium-catalysed direct substitution of alcohols: enhancing the selectivity by kinetic analysis
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Kinetic analysis was used as a tool for rational optimization of a catalytic, direct substitution of alcohols to enable the selective formation of unsymmetrical ethers, thioethers, and Friedel-Crafts alkylation products using a moisture-tolerant and commercially available zirconium complex (2 to 8 mol%). Operating in air and in the absence of dehydration techniques, the protocol furnished a variety of products in high yields, including glycosylated alcohols and sterically hindered ethers. In addition, the kinetic studies provided mechanistic insight into the network of parallel transformations that take place in the reaction, and helped to elucidate the nature of the operating catalyst.
- Camaj, David,Carlsson, Robin,Dalla-Santa, Oscar,Lill, Malin,Lundberg, Helena,Margarita, Cristiana,Ramstr?m, Anja,Tu?on, Hernando,Villo, Piret
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p. 7420 - 7430
(2021/11/23)
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- Regioselective Gold-Catalyzed Hydration of CF3- and SF5-alkynes
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The regioselective gold-catalyzed hydration of CF3- and SF5-alkynes is described. The corresponding trifluoromethylated and pentasulfanylated ketones are obtained in up to 91% yield as single regioisomers showcasing the use of CF3 and SF5 as highly efficient directing groups in this reaction. Notably, this transformation represents the first use of CF3- and SF5-alkynes in gold catalysis.
- Cloutier, Mélissa,Roudias, Majdouline,Paquin, Jean-Fran?ois
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supporting information
p. 3866 - 3870
(2019/05/24)
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- Copper(I)-catalyzed stereoselective hydrogenation of 1,3-diynes and enynes
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A stereoselective hydrogenation of 1,3-diynes with an air-stable copper(I)/N-heterocyclic carbene complex, [IPrCuOH], has been developed. The corresponding products, 1,3-dienes, are obtained in a stereoselective manner depending on their substitution pattern: Diaryl-diynes yield E,E-1,3-dienes, whereas dialkyl-diynes are converted to the corresponding Z,Z-1,3-dienes. Hydrogenation and deuteration experiments with enynes indicate that these are competent reaction intermediates in the hydrogenation of diynes.
- Thiel, Niklas O.,Kemper, Sebastian,Teichert, Johannes F.
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supporting information
p. 5023 - 5028
(2017/07/27)
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- Pyrrolidine compounds, salts thereof, applications of compounds or salts thereof in nuclear magnetic probes and medicines, reagent, and medicine
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The invention provides pyrrolidine compounds, salts thereof, applications of the compounds or the salts thereof in nuclear magnetic probes and medicines, a reagent, and a medicine. The benzamide methylpyrrolidine compounds have a chemical structure represented by general formula (I); and in the formula (I), R is selected from a methyl group, an ethyl group, a methoxy group, an ethoxy group and halogen, R is selected from a methyl group, an ethyl group, a methoxy group, an ethoxy group and halogen, R is selected from C1-5 alkyl groups and H, X is selected from C1-10 alkylene groups or is deleted, X is selected from -(CH2CH2O)n- (n is 1-5) or is deleted, X is selected from C1-5 alkyl groups, X is selected from oxygen, sulfur and a methylene group, and Ln is selected from Gd and Eu. The compounds have a gadolinium and europium chelating structure formed by combining with a dopamine D2 receptor and depending on intramolecular chelating groups, and specifically enhance the contrast of dopamine D2 receptor expression tissues on images in magnetic resonance imaging.
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Paragraph 0097; 0098; 0099
(2017/08/27)
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- Radical Hydrodeiodination of Aryl, Alkenyl, Alkynyl, and Alkyl Iodides with an Alcoholate as Organic Chain Reductant through Electron Catalysis
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A simple and efficient method for radical hydrodeiodination is reported. The novel approach uses electron catalysis. In situ generated Na-alcoholates are introduced as radical chain reducing reagents and reactions work with O2as cheap initiator. Hydrodeiodination works on aryl, alkenyl, alkynyl iodides and a tert-alkyl iodide also gets reduced applying the method. Albeit less general, the method is also applicable to the reduction of aryl bromides. The novel reagent is successfully used to conduct typical reductive radical cyclization reactions and mechanistic studies are reported.
- Dewanji, Abhishek,Mück-Lichtenfeld, Christian,Studer, Armido
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p. 6749 - 6752
(2016/06/09)
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- Stereoselective synthesis of conjugated trienols from allylic alcohols and 1-iodo-1,3-dienes
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The stereoselective synthesis of conjugated trienes has been achieved from allylic alcohols and 1-iodo-1,3-dienes using Pd(OAc)2/AgOAc.
- Brandt, Damien,Bellosta, Veronique,Cossy, Janine
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supporting information
p. 5594 - 5597,4
(2012/12/12)
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- Synthesis and evaluation of cyclic RGD-boron cluster conjugates to develop tumor-selective boron carriers for boron neutron capture therapy
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Boron-containing agents play a key role in successful boron neutron capture therapy (BNCT). Icosahedral boron cluster-Arg-Gly-Asp (RGD) peptide conjugates were designed, synthesized, and evaluated for the biodistribution to develop tumor-selective boron c
- Kimura, Sadaaki,Masunaga, Shin-Ichiro,Harada, Tomohiro,Kawamura, Yasuo,Ueda, Satoshi,Okuda, Kensuke,Nagasawa, Hideko
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supporting information; experimental part
p. 1721 - 1728
(2011/04/18)
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- Total synthesis of (+)-nankakurines A and B and (±)-5-epi- nankakurine A
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The first total syntheses of the Lycopodium alkaloids (+)-nankakurine A (2), (+)-nankakurine B (3), and the originally purported structure 1 of nankakurine A were accomplished. The syntheses of 2 and 3 feature a demanding intramolecular azomethine imine cycloaddition as the key step for generating the octahydro-3,5-ethanoquinoline moiety and installing the correct relative configuration at the spiropiperidine ring juncture. The cyclization precursor was prepared from octahydronaphthalene ketone 50, which was assembled from enone (+)-9 and diene 48 by a cationic Diels-Alder reaction. The Diels-Alder reactants were synthesized from 5-hexyn-1-ol (16) and (+)-pulegone (49), respectively. The tetracyclic ring system of 1 was generated using an unprecedented nitrogen-terminated aza-Prins cyclization cascade. The enantioselective total syntheses of (+)-nankakurine A (2) and (+)-nankakurine B (3) establish the relative and absolute configuration of these alkaloids and are sufficiently concise that substantial quantities of 2 and 3 were prepared for biological studies. (+)-Nankakurine A and (+)-nankakurine B showed no effect on neurite outgrowth in rat hippocampal H-19 cells over a concentration range of 0.3-10 μM.
- Altman, Ryan A.,Nilsson, Bradley L.,Overman, Larry E.,Read De Alaniz, Javier,Rohde, Jason M.,Taupin, Veronique
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experimental part
p. 7519 - 7534
(2011/02/23)
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- Enantioselective total syntheses of nankakurines A and B: Confirmation of structure and establishment of absolute configuration
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Total syntheses of (+)-nankakurine A (2) and (+)-nankakurine B (3) were accomplished by a sequence that employs an intramolecular dipolar cycloaddition of an azomethine imine intermediate to form the azatricyclic moiety and establish the relative configur
- Nilsson, Bradley L.,Overman, Larry E.,De Alaniz, Javier Read,Rohde, Jason M.
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supporting information; experimental part
p. 11297 - 11299
(2018/02/14)
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- Anti-hypercholesterolemic biaryl azetidinone compounds
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This invention provides cholesterol absorption inhibitors of Formula I: and the pharmaceutically acceptable salts thereof, wherein R12 is an alkyl, alkeny or alkynyl group mono- or poly-substituted with —OH, —COOH or a combination of —OH and —COOH, and R9 contains an alkyl, alkeny or alkynyl group substituted with a heterocyclic ring, amino or sulfonyl. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating atherosclerosis and preventing atherosclerotic disease events.
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Page/Page column 23
(2008/12/08)
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- Tetrabutylammonium fluoride-induced dehydrobromination of vinyl bromides to terminal acetylenes
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Tetrabutylammonium fluoride (TBAF) was found to be a mild and efficient base for the dehydrobromination of vinyl bromides. Treatment of various 2-bromo-1-alkenes with TBAF·3H2O in DMF yielded terminal acetylenes in high yields without undue regard to the presence of water.
- Okutani, Masaru,Mori, Yuji
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p. 6856 - 6859
(2008/02/12)
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- Anti-hypercholesterolemic compounds
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This invention provides cholesterol absorption inhibitors of Formula I: and the pharmaceutically acceptable salts and esters thereof. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating and preventing atherosclerosis and atherosclerotic disease events.
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Page/Page column 14
(2008/06/13)
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- Synthesis of (R)- and (S)-10,16-dihydroxyhexadecanoic acid: Cutin stereochemistry and fungal activation
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The first asymmetric syntheses of the cutin monomers (R)- and (S)-10,16-dihydroxyhexadecanoic acid (10,16-DHPA) and confirmation of (S)(+)-absolute configuration for 10, 16-DHPA derived from tomato are reported. The individual DHPA stereoisomers display differences in their ability to activate the fungal pathogen Colletotrichum trifolii.
- Ahmed, Aqeel,Crawford, Terry,Gould, Stephanie,Ha,Hollrah, Monica,Noor-E-Ain, Farhana,Dickman, Martin B.,Dussault, Patrick H.
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- Generation and reactions of alkynylsamariums
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Three methods have been developed for generating alkynylsamariums: (1) reduction of iodoalkynes with SmI2 in the presence of HMPA, (2) deprotonation at the terminal position of 1-alkynes either by tetrahydrofurylsamarium generated by PhI and Sm
- Kunishima, Munetaka,Nakata, Daisuke,Tanaka, Shinobu,Hioki, Kazuhito,Tani, Shohei
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p. 9927 - 9935
(2007/10/03)
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- Acid-catalyzed cyclization of vinylsilanes bearing a hydroxy group: A new method for stereoselective synthesis of disubstituted tetrahydrofurans
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In the presence of a catalytic amount of TsOH or TiCl4, (Z)-5-silyl-4-penten-1-ols ((Z)-1) are smoothly cyclized to 2-silylmethyl-substituted tetrahydrofurans. This cyclization is applicable to the construction of a tetrahydropyran ring. The silyl group and the geometry of the C-C double bond strongly influence the cychzation rate. TBDMS and benzyldimethylsilyl groups considerably accelerate the cyclization in comparison with a dimethylphenylsilyl group, and (E)-vinylsilanes show much lower reactivity than the corresponding (Z)-isomers. The cyclization proceeds by stereospecific syn addition of the hydroxy group. Vinylsilanes 17, 19, and 21, (Z)-5-silyl-4-penten-1-ols bearing a substituent on the methylene tether, smoothly undergo the acid-catalyzed cyclization to give trans-2,5-, cis-2,4-, and trans-2,3-disubstituted tetrahydrofurans, respectively, with moderate to high stereoselectivity. The silyl group of some cychzed products can be easily converted into a hydroxy group with stereochemical retention.
- Miura,Okajima,Hondo,Nakagawa,Takahashi,Hosomi
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p. 11348 - 11357
(2007/10/03)
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