- A CO2-Catalyzed Transamidation Reaction
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Transamidation reactions are often mediated by reactive substrates in the presence of overstoichiometric activating reagents and/or transition metal catalysts. Here we report the use of CO2as a traceless catalyst: in the presence of catalytic amounts of CO2, transamidation reactions were accelerated with primary, secondary, and tertiary amide donors. Various amine nucleophiles including amino acid derivatives were tolerated, showcasing the utility of transamidation in peptide modification and polymer degradation (e.g., Nylon-6,6). In particular,N,O-dimethylhydroxyl amides (Weinreb amides) displayed a distinct reactivity in the CO2-catalyzed transamidation versus a N2atmosphere. Comparative Hammett studies and kinetic analysis were conducted to elucidate the catalytic activation mechanism of molecular CO2, which was supported by DFT calculations. We attributed the positive effect of CO2in the transamidation reaction to the stabilization of tetrahedral intermediates by covalent binding to the electrophilic CO2
- Yang, Yang,Liu, Jian,Kamounah, Fadhil S.,Ciancaleoni, Gianluca,Lee, Ji-Woong
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p. 16867 - 16881
(2021/11/18)
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- Saturated Bioisosteres of ortho-Substituted Benzenes
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Saturated bioisosteres of ortho-disubstituted benzenes (bicyclo[2.1.1]hexanes) were synthesized, characterized and validated. These cores were incorporated into the bioactive compounds Valsartan, Boskalid and Fluxapyroxad instead of the benzene ring. The
- Denisenko, Aleksandr,Garbuz, Pavel,Mykhailiuk, Pavel K.,Shishkina, Svetlana V.,Voloshchuk, Nataliya M.
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supporting information
p. 20515 - 20521
(2020/08/21)
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- One-pot synthesis of Weinreb amides employing 3,3-dichloro-1,2-diphenylcyclopropene (CPI-Cl) as a chlorinating agent
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The synthesis of Nα-protected amino alkyl Weinreb amides starting from the corresponding α-amino acids as well as carboxylic acids has been delineated through the in situ generation of acid chlorides using CPI-Cl as a chlorinating agent. The protocol is simple; the reaction conditions employed were mild, and compatible with all the three commonly used urethane protecting groups namely, Boc, Cbz and Fmoc groups. The resulting Weinreb amides are obtained in good yields as optically pure products.
- Shekharappa,Roopesh Kumar,Sureshbabu, Vommina V.
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supporting information
p. 790 - 798
(2019/03/26)
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- Iminyl Radicals by Reductive Cleavage of N-O Bond in Oxime Ether Promoted by SmI2: A Straightforward Synthesis of Five-Membered Cyclic Imines
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A new generation method of N-centered radicals from the reductive cleavage of the N-O bond in oxime ether promoted by SmI2 is reported for the first time. The in-situ-generated N-centered radicals underwent intramolecular cyclization to afford five-membered cyclic imines in two manners: N-centered radical addition and N-centered anion nucleophilic substitution. From a synthetic point of view, an efficient synthetic method of five-membered cyclic imines was developed. A mechanism of the transformation was proposed.
- Huang, Fei,Zhang, Songlin
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supporting information
p. 7430 - 7434
(2019/10/11)
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- Design, synthesis and biological evaluation of anti-pancreatic cancer activity of plinabulin derivatives based on the co-crystal structure
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Based on the co-crystal structures of tubulin with plinabulin and Compound 1 (a derivative of plinabulin), a total of 18 novel plinabulin derivatives were designed and synthesized. Their biological activities were evaluated against human pancreatic cancer BxPC-3 cell lines. Two novel Compounds 13d and 13e exhibited potent activities with IC50 at 1.56 and 1.72 nM, respectively. The tubulin polymerization assay indicated that these derivatives could inhibit microtubule polymerization. Furthermore, the interaction between tubulin and these compounds were elucidated by molecular docking. The binding modes of Compounds 13d and 13e were similar to the co-crystal structure of Compound 1. H-π interaction was observed between the aromatic hydrogen of thiophene moiety with Phe20, which could enhance their binding affinities.
- Fu, Zhangyu,Hou, Yingwei,Ji, Cunpeng,Ma, Mingxu,Tian, Zhenhua,Deng, Mengyan,Zhong, Lili,Chu, Yanyan,Li, Wenbao
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p. 2061 - 2072
(2018/03/26)
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- Mo(CO)6 as a Solid CO Source in the Synthesis of Aryl/Heteroaryl Weinreb Amides under Microwave-Enhanced Condition
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The facile transformation of aryl/heteroaryl nonaflates into corresponding amides via Pd-catalyzed aminocarbonylation using Mo(CO)6 as a solid CO source under microwave-enhanced condition is reported. The method was found to be tolerant with respect to a
- Ningegowda, Raghu,Bhaskaran, Savitha,Sajith, Ayyiliath M.,Aswathanarayanappa, Chandrashekar,Padusha, M. Syed Ali,Priya, Babu Shubha
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- One-Pot Direct Synthesis of Weinreb Amides from Aryl and Hetero Aryl Halides Using Co 2(CO) 8 as an Effective CO Source under Conventional Thermal Heating
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A successful protocol for the synthesis of Weinreb amides directly from aryl halides via aminocarbonylation with N,O-dimethyl hydroxylamine using Co2(CO)8 as an in situ CO source has been demonstrated. The effects of various reaction parameters such as temperature, base, and CO source have also been investigated and optimized. GRAPHICAL ABSTRACT.
- Baburajan, Poongavanam,Elango, Kuppanagounder P.
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p. 541 - 548
(2015/10/29)
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- An Efficient synthesis of Weinreb amides and ketones via palladium nanoparticles on ZIF-8 catalysed carbonylative coupling
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Heterogeneously catalysed carbonylative coupling reactions such as aminocarbonylation and Suzuki-carbonylation are reported using Pd nanoparticles supported on ZIF-8 for efficient and environmentally attractive synthesis of Weinreb amides and ketones from aryl bromides or iodides. The catalyst is air stable, offers high activity with very low palladium leaching and is recyclable. The presence of a phosphine ligand was required when aryl bromides were used as substrates, while no ligand was necessary when aryl iodides were used. the Partner Organisations 2014.
- Thanh Dang, Tuan,Chen, Anqi,Majeed Seayad, Abdul
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p. 30019 - 30027
(2014/08/05)
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- HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt
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The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.
- -
-
Paragraph 0274; 0275; 0278; 0279
(2014/05/07)
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- Analogues of fenarimol are potent inhibitors of trypanosoma cruzi and are efficacious in a murine model of chagas disease
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We report the discovery of nontoxic fungicide fenarimol (1) as an inhibitor of Trypanosoma cruzi (T. cruzi), the causative agent of Chagas disease, and the results of structure-activity investigations leading to potent analogues with low nM IC50s in a T. cruzi whole cell in vitro assay. Lead compounds suppressed blood parasitemia to virtually undetectable levels after once daily oral dosing in mouse models of T. cruzi infection. Compounds are chemically tractable, allowing rapid optimization of target biological activity and drug characteristics. Chemical and biological studies undertaken in the development of the fenarimol series toward the goal of delivering a new drug candidate for Chagas disease are reported.
- Keenan, Martine,Abbott, Michael J.,Alexander, Paul W.,Armstrong, Tanya,Best, Wayne M.,Berven, Bradley,Botero, Adriana,Chaplin, Jason H.,Charman, Susan A.,Chatelain, Eric,Von Geldern, Thomas W.,Kerfoot, Maria,Khong, Andrea,Nguyen, Tien,McManus, Joshua D.,Morizzi, Julia,Ryan, Eileen,Scandale, Ivan,Thompson, R. Andrew,Wang, Sen Z.,White, Karen L.
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supporting information; experimental part
p. 4189 - 4204
(2012/07/27)
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- NOVEL DIHYDROPYRIMIDIN-2(1H)-ONE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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The present invention is directed to novel dihydropyrimidin-2(1H)-one compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.
- -
-
Page/Page column 144
(2011/04/24)
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- Synthesis and antiproliferative activity of pyridinylcarbonylpyrimidines against melanoma cell line
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The synthesis of the series of pyrimidinylamines 1a-d and pyrimidinylureas 1e-u bearing a novel pyridinylcarbonylpyrimidine scaffold and their antiproliferative activities against A375 human melanoma cell line were described. Among them, three compounds 1
- Ahn, Hyemi,Lee, Jun A.,Kim, Hwan,Oh, Chang-Hyun,Lee, So Ha,Sim, Taebo,Hah, Jung-Mi,Kim, Dong Jin,Yoo, Kyung Ho
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experimental part
p. 1209 - 1214
(2011/11/06)
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- Access to the nicotine system by application of a guanidine-catalyzed asymmetric Michael addition of diphenyliminoacetate with 3-pyridyl vinyl ketone
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A guanidine-based chiral organocatalyst was successfully applied to the Michael addition of diphenyliminoacetate to pyridyl vinyl ketone as a key reaction for the construction of the nicotine system.
- Zhang, Gang,Kumamoto, Takuya,Heima, Takashi,Ishikawa, Tsutomu
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scheme or table
p. 3927 - 3930
(2010/08/20)
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- Discovery of CYT997: a structurally novel orally active microtubule targeting agent
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CYT997 was discovered as a potent tubulin polymerization inhibitor possessing potent cytotoxic activity against a range of cancer cells. Details of SAR studies, pharmacokinetic investigations and synthesis of compounds leading to the discovery of CYT997 a
- Burns, Christopher J.,Harte, Michael F.,Bu, Xianyong,Fantino, Emmanuelle,Joffe, Max,Sikanyika, Harrison,Su, Stephen,Tranberg, C. Elisabet,Wilson, Neil,Charman, Susan A.,Shackleford, David M.,Wilks, Andrew F.
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scheme or table
p. 4639 - 4642
(2010/04/28)
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- ORGANIC COMPOUNDS
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The present invention provides novel organic compounds of Formula (I): methods of use, and pharmaceutical compositions thereof.
- -
-
Page/Page column 78-79
(2011/04/19)
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- HETEROCYCLIC COMPOUNDS WITH AFFINITY TO MUSCARINIC RECEPTORS
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The present invention relates to heterocyclic compounds of the formula (I) wherein - the heterocycle comprises two double bonds which may be present at several positions, represented by the dashed lines ( -- ); - the heterocycle contains two heteroatoms,
- -
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Page/Page column 28
(2008/12/08)
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- A facile one-pot synthesis of acyclic β-enamino ketones, an important class of versatile synthetic intermediates
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A one-pot sequential process consisting of nucleophilic substitution of the lithiated acetylides with Weinreb amides followed by a Michael reaction of the extruded N-methoxy-N-methylamine after quenching with saturated NH4Cl, provided β-enamino ketones in high yield and in a single geometrical isomeric form. It has been demonstrated that this method is applicable to a wide variety of such amides and to different acetylides.
- Choudhury, Anusuya,Breslav, Michael,Grimm, Jeffrey S.,Xiao, Tong,Xu, Dawei,Sorgi, Kirk L.
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p. 3069 - 3072
(2008/02/02)
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- SUBSTITUTED N-ARYLPYRROLIDINES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
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The present invention provides a compound of the formula: Formula I or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising an effective amount of a compound of Formula I in combination with a suitable carrier, diluent, or excipient; and methods for treating physiological disorders, particularly frailty, osteoporosis, osteopenia, and male and female sexual dysfunction comprising administering to a patient in need thereof an effective amount of a compound of Formula I.
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Page/Page column 77
(2010/11/25)
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- HETEROCYCLIC ANTI-VIRAL COMPOUNDS COMPRISING METABOLIZABLE MOIETIES AND THEIR USES
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The present invention relates to substituted prodrug and compositions thereof useful for treating or preventing Hepatitis C virus (HCV) infections. In particular, the present invention relates to prodrugs of substituted diphenyl-, diheteroaryl- and mixed phenyl heteroaryl substituted five-membered heterocycle compounds, compositions comprising the compounds and the use of such compounds and compositions to inhibit HCV replication and/or proliferation as a therapeutic approach towards the treatment and/or prevention of HCV infections in humans and animals.
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Page/Page column 63; 17/24
(2010/02/14)
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- NH vs. CH hydrogen bond formation in metal-organic anion receptors containing pyrrolylpyridine ligands
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Anion complexation studies on a series of platinum(II) tetrakis(pyrrolylpyridine) salts demonstrate the importance of CH-anion hydrogen bonds in coordinating anionic guests in solution and the solid-state. The Royal Society of Chemistry 2005.
- Vega, Ismael El Drubi,Gale, Philip A.,Light, Mark E.,Loeb, Stephen J.
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p. 4913 - 4915
(2007/10/03)
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- Synthesis of nornicotine, nicotine and other functionalised derivatives using solid-supported reagents and scavengers
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The sequential use of solid-supported reagents and scavengers has led to an efficient synthesis of the natural products nornicotine 1, nicotine 2 and further fuctionalised derivatives. Also reported is a diastereoselective route to both enantiomers of nicotine 2.
- Baxendale, Ian R.,Brusotti, Gloria,Matsuoka, Masato,Ley, Steven V.
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p. 143 - 154
(2007/10/03)
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- Observations on the DDQ oxidation of 1-acyldihydropyridines - A synthetic application
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A synthetic application of the rate difference in oxidation of regioisomerically substituted N-acyldihydropyridines is reported. This has allowed for isolation of pure 4-substituted pyridine isomers without the need for chromatography. Diels-Alder adducts between a dihydropyridine and DDQ were isolated and formation of novel hydroquinone ethers was also observed during some reactions.
- Wallace,Gibb,Cottrell,Kennedy,Brands,Dolling
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p. 1784 - 1789
(2007/10/03)
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- A concise route to novel 1-aryl and 1-pyridyl-2-azabicyclo[2.1.1]hexanes
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A number of novel 1-aryl and 1-pyridyl-2-azabicyclo[2.1.1]hexane derivatives were prepared by an intramolecular [2+2] photocycloaddition in the presence of acetophenone as the sensitizer. Substitution of the azabicyclo[2.1.1]hexane ring was accomplished by appropriate choice of the heteroaryl ketone and allylamine starting materials. Several aryl 9a-e, g and pyridyl analogs 9h-l were prepared by this method. The structures of 9a and 9i were verified by X-ray crystallography. Several of the photoproducts 9 were converted into the corresponding N-Me and N-H 2,4-methanonicotine analogs 4 by reduction or hydrolysis of the N-carboethoxy group.
- Piotrowski, David W.
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p. 1091 - 1093
(2007/10/03)
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- Convenient conversion of acid to Weinreb's amide
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Various carboxylic acids are converted to their corresponding N-methoxy- N-methyl amides through tile mixed anhydride formed by their reaction with pivaloyl chloride.
- Raghuram,Vijaysaradhi,Singh, Indrapal,Singh, Jaimala
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p. 3215 - 3219
(2007/10/03)
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