- Switchable Oxidative Reactions of N-allyl-2-Aminophenols: Palladium-Catalyzed Alkoxyacyloxylation vs an Intramolecular Diels-Alder Reaction
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The Pd(II)-catalyzed reaction of N-allyl-2-aminophenols in the presence of PhI(OCOR)2 as the oxidant resulted in an alkoxyacyloxylation process, with the formation of functionalized dihydro-1,4-benzoxazines. The reaction performed in the absence of pallad
- Beccalli, Egle M.,Giofrè, Sabrina,Keller, Manfred,Lo Presti, Leonardo,Molteni, Letizia
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supporting information
p. 7698 - 7702
(2021/10/25)
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- Structure-activity relationships of natural quinone vegfrecine analogs with potent activity against VEGFR-1 and -2 tyrosine kinases
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A series of analogs of vegfrecine, a natural quinone vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor, was synthesized via oxidative amination of 2,5-dihydroxybenzamide with functionalized arylamine followed by ammonolysis and
- Adachi, Hayamitsu,Nosaka, Chisato,Atsumi, Sonoko,Nakae, Koichi,Umezawa, Yoji,Sawa, Ryuichi,Kubota, Yumiko,Nakane, Chie,Shibuya, Masabumi,Nishimura, Yoshio
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p. 734 - 742
(2021/07/25)
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- Nickel-catalyzed reductive aryl thiocarbonylation of alkene via thioester group transfer strategy
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Herein reported is a nickel-catalyzed reductive aryl thiocarbonylation of alkene via thioester group transfer strategy by using simple and readily available thioesters. In contrast to traditional activation of weaker C(acyl)-S bond, the C(acyl)-C bond of
- Feng, Yunxia,Yang, Shimin,Zhao, Shen,Zhang, Dao-Peng,Li, Xinjin,Liu, Hui,Dong, Yunhui,Sun, Feng-Gang
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supporting information
p. 6734 - 6738
(2020/09/15)
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- Analysis of chain length, substitution patterns, and unsaturation of AM-404 derivatives as 20S proteasome stimulators
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Proteasome-mediated degradation of proteins is a vital cellular process and is performed by the ubiquitin-dependent proteasome system (UPS) and the ubiquitin-independent proteasome system (UIPS). While both systems are necessary to maintain healthy cell function, many disease states are characterized by reduced activity of the UPS, and the UIPS cannot by itself maintain proper protein levels. It has been suggested that the 20S core particle (20S CP), the isoform of the proteasome in the UIPS that can degrade proteins without a ubiquitin tag, can be stimulated with a small molecule to assist the 20S CP to accept and hydrolyze substrates more rapidly. Several small molecule stimulators of the 20S CP have since been discovered, including AM-404, an arachidonic acid derivative. AM-404 has previously been shown to inhibit fatty acid amide hydrolase activity. We wished to evaluate what structural components of AM-404 are required to stimulate the 20S CP with the long-term goal of using this information to design a stimulator with better drug-like qualities. We synthesized numerous derivatives of AM-404, varying the chain length, substitutions, and degree of unsaturation. Through this endeavor, we obtained several molecules capable of stimulating the 20S CP to various degrees. We discovered that though chain length is important, the presence of a cis-alkene in a specific location in the aliphatic chain has the greatest impact on the ability to stimulate the 20S CP. Two of the derivatives maintain modest stimulatory activity, and have improved toxicity over AM-404.
- Coleman, Rachel A.,Muli, Christine S.,Zhao, Yizhou,Bhardwaj, Atul,Newhouse, Timothy R.,Trader, Darci J.
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supporting information
p. 420 - 423
(2019/01/04)
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- Nickel-Catalyzed Domino Heck Cyclization/Suzuki Coupling for the Synthesis of 3,3-Disubstituted Oxindoles
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The first nickel-catalyzed domino Heck cyclization/Suzuki coupling reaction for the synthesis of 3,3-disubstituted oxindoles bearing quaternary all-carbon centers is reported. A wide range of electrophiles, such as aryl iodides, bromides, triflates, and c
- Li, Yuxiu,Wang, Kuai,Ping, Yuanyuan,Wang, Yifan,Kong, Wangqing
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supporting information
p. 921 - 924
(2018/02/22)
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- Water as a Hydride Source in Palladium-Catalyzed Enantioselective Reductive Heck Reactions
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Pd-catalyzed intramolecular asymmetric carbopalladation of N-aryl acrylamides followed by reduction of C(sp3)-Pd intermediate using diboron–water as a hydride source afforded enantioenriched 3,3-disubstituted oxindoles in high yields and enantioselectivities. When heavy water was used as a deuterium donor in combination with bis(catecholato)diboron (Cat2B2), deuterium was incorporated into the products with high synthetic efficiency. The ligand determined both the enantioselectivity of the reaction and the reaction pathways, thereby affording either hydroarylation (reductive Heck) or carboborylation products.
- Kong, Wangqing,Wang, Qian,Zhu, Jieping
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supporting information
p. 3987 - 3991
(2017/03/27)
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- Highly chemoselective reduction of azides to amines by Fe(0) nanoparticles in water at room temperature
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A highly chemoselective reduction of aryl, heteroaryl, acyl and sulfonyl azides to the corresponding amines has been achieved by Fe(0) nanoparticles in water at room temperature in the absence of external hydride source. Several readily reducible functionalities including alkene, alkyne, S-S linkage, OTBDMS remain unaffected during reduction.
- Panja, Subir,kundu, Debasish,Ahammed, Sabir,Ranu, Brindaban C.
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supporting information
p. 3457 - 3460
(2017/08/10)
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- Fe-Catalyzed Amination of (Hetero)Arenes with a Redox-Active Aminating Reagent under Mild Conditions
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A novel and efficient Fe-catalyzed direct C?H amination (NH2) of arenes is reported using a new redox-active aminating reagent. The reaction is simple, and can be performed under air, mild, and redox-neutral conditions. This protocol has a broad substrate scope and could be used in the late-stage modification of bioactive compounds. Mechanistic studies demonstrate that a radical pathway could be involved in this transformation.
- Liu, Jianzhong,Wu, Kai,Shen, Tao,Liang, Yujie,Zou, Miancheng,Zhu, Yuchao,Li, Xinwei,Li, Xinyao,Jiao, Ning
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supporting information
p. 563 - 567
(2017/01/18)
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- Direct Amidation of N-Boc- and N-Cbz-Protected Amines via Rhodium-Catalyzed Coupling of Arylboroxines and Carbamates
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N-Boc- and N-Cbz-protected amines are directly converted into amides by a novel rhodium-catalyzed coupling of arylboroxines and carbamates, replacing the traditional two-step deprotection-condensation sequence. Both protected anilines and aliphatic amines are efficiently transformed into a wide variety of secondary benzamides, including sterically hindered and electron-deficient amides, as well as in the presence of acid-labile and reducible functional groups.
- Lim, Diane S. W.,Lew, Tedrick T. S.,Zhang, Yugen
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supporting information
p. 6054 - 6057
(2016/01/09)
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- Palladium-Catalyzed Enantioselective Domino Heck/Intermolecular C-H Bond Functionalization: Development and Application to the Synthesis of (+)-Esermethole
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Intramolecular asymmetric carbopalladation of N-aryl acrylamides followed by intermolecular trapping of the resulting -C(sp3)-Pd complex by azoles afforded 3,3-disubstituted oxindoles in good yields with excellent enantioselectivities. Two C-C bonds were created with concurrent formation of an all-carbon quaternary stereocenter. Oxadiazole substituted oxindoles were subsequently converted to pyrroloindolines by an unprecedented reductive cyclization protocol. The utility of this chemistry was illustrated by an enantioselective synthesis of (+)-esermethole.
- Kong, Wangqing,Wang, Qian,Zhu, Jieping
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supporting information
p. 16028 - 16031
(2016/01/15)
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- Site-selective arene C-H amination via photoredox catalysis
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Over the past several decades, organometallic cross-coupling chemistry has developed into one of the most reliable approaches to assemble complex aromatic compounds from preoxidized starting materials. More recently, transition metal-catalyzed carbon-hydrogen activation has circumvented the need for preoxidized starting materials, but this approach is limited by a lack of practical amination protocols. Here, we present a blueprint for aromatic carbon-hydrogen functionalization via photoredox catalysis and describe the utility of this strategy for arene amination. An organic photoredox-based catalyst system, consisting of an acridinium photooxidant and a nitroxyl radical, promotes site-selective amination of a variety of simple and complex aromatics with heteroaromatic azoles of interest in pharmaceutical research. We also describe the atom-economical use of ammonia to form anilines, without the need for prefunctionalization of the aromatic component.
- Romero, Nathan A.,Margrey, Kaila A.,Tay, Nicholas E.,Nicewicz, David A.
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p. 1326 - 1330
(2015/10/12)
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- Synthesis of novel N-(2-Hydroxyphenyl)arylsulfonamides as selective HDAC inhibitory and cytotoxic agents
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Based on the finding that the 2-aminobenzamido group of MS-275 plays a crucial role in inhibiting HDACs through chelation of zinc existing at the active site of HDAC enzymes, novel N-(2-hydroxyphenyl)aryl-sulfonamide derivatives were synthesized for their potential ability to inhibit HDACs and evaluated for anticancer activity against human breast cancer cell line (MCF-7). Although the synthesized arylsulfonamides have failed to significantly inhibit total HDACs activity, phenyl carbamate-linked arylsulfonamide 10 and benzyl thiocarbamate-linked arylsulfonamide 15 exhibited good anticancer activities, which were only 4.3- and 3.6-fold lower anticancer activities, respectively, than MS-275 that is undergoing phase II clinical trials. These results suggest that these compounds may act as a selective HDAC inhibitor and probably N-(2-hydroxy-phenyl)sulfamoyl group may play an important role in interacting with HDAC enzymes through chelation of zinc ion.
- Kim, Jungsu,Chun, Pusoon,Moon, Hyung Ryong
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p. 1487 - 1493
(2013/07/28)
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- Enantioselective synthesis of benzofurans and benzoxazines via an olefin cross-metathesis-intramolecular oxo-Michael reaction
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Chiral phosphoric acid and Hoveyda-Grubbs II were found to catalyze an olefin cross-metathesis-intramolecular oxo-Michael cascade reaction of the ortho-allylphenols and enones to provide a variety of benzofuran and benzoxazine derivatives in moderate to good yields and enantioselectivity.
- Zhang, Jun-Wei,Cai, Quan,Gu, Qing,Shi, Xiao-Xin,You, Shu-Li
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supporting information
p. 7750 - 7752
(2013/09/02)
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- Vegfrecine, an inhibitor of VEGF receptor tyrosine kinases isolated from the culture broth of Streptomyces sp.
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A new inhibitor of VEGF receptor tyrosine kinases, vegfrecine (1), was isolated from the culture broth of Streptomyces sp. MK931-CF8. The molecular structure of 1 was determined by NMR and MS analysis combined with synthesis. Compound 1 showed potent inhi
- Nosaka, Chisato,Adachi, Hayamitsu,Sawa, Ryuichi,Nakae, Koichi,Atsumi, Sonoko,Kinoshita, Naoko,Kubota, Yumiko,Igarashi, Masayuki,Sei, Yoshihisa,Yamaguchi, Kentaro,Shibuya, Masabumi,Nishimura, Yoshio,Akamatsu, Yuzuru
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p. 715 - 719
(2013/06/05)
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- Isolation and synthesis of allelochemicals from gramineae: Benzoxazinones and related compounds
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Compounds with a (2H)-1,4-benzoxazin-3(4H)-one skeleton have attracted the attention of phytochemistry researchers since 2,4-dihydroxy-(2H)-1,4-benzoxazin- 3(4H)-one (DIBOA) and 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) were isolated from plants belonging to the Poaceae family. These compounds exhibit interesting biological properties, such as phytotoxic, antimicrobial, antifeedant, antifungal, and insecticidal properties. These chemicals, in addition to a wide variety of related compounds involved in their metabolism, detoxification mechanisms, and degradation on crop soils and other systems, have high interest and in some cases potential agronomic utility. This paper presents a complete review of the methods employed for their synthetic obtention in addition to some of the authors' own contributions to their chemistry. The degradation and phytotoxicity experiments carried out in ongoing research into the potential agronomic utility of these compounds required large amounts of them, which were obtained from natural sources. This paper presents a modified methodology to access DIMBOA from Zea mays cv. Apache and to obtain 2-O-β-D-glucopyranosyl-2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA-Glc) and DIBOA from Secale cereale L. New synthetic methodologies were employed for the obtention of the lactams 2-hydroxy-(2H)-1,4-benzoxazin-3(4H)- one and 2-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one and the malonamic acids N-(2-hydroxyphenyl)malonamic acid and N-(2-hydroxy-7-methoxyphenyl)- malonamic acid. The aminophenoxazines 2-amino-7-methoxyphenoxazin-3-one and 2-acetamido-7-methoxyphenoxazin-3-one have been synthesized in the authors' laboratory by novel procedures. All of the methodologies employed allowed the desired compounds to be obtained in high yield and in an easy-to-scale manner.
- Macias, Francisco A.,Marin, David,Oliveros-Bastidas, Alberto,Chinchilla, David,Simonet, Ana M.,Molinillo, Jose M. G.
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p. 991 - 1000
(2007/10/03)
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- Structure-activity relationships (SAR) studies of benzoxazinones, their degradation products and analogues. Phytotoxicity on standard target species (STS)
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Benzoxazinones 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA) and 2,4-dihydroxy-(2H)-1,4-benzoxazin-3(4H)-one (DIBOA) have been considered key compounds for understanding allelopathic phenomena in Gramineae crop plants such as corn (Zea mays L.), wheat (Triticum aestivum L.), and rye (Secale cereale L.). The degradation processes in the environment observed for these compounds, in which soil microbes are directly involved, could affect potential allelopathic activity of these plants. We present in this work a complete structure-activity relationships study based on the phytotoxic effects observed for DIMBOA, DIBOA, and their main degradation products, in addition to several synthetic analogues of them. Their effects were evaluated on standard target species (STS), which include Triticum aestivum L. (wheat) and Allium cepa L. (onion) as monocots and Lepidium sativum L. (cress), Lactuca sativa L. (lettuce), and Lycopersicon esculentum Will, (tomato) as dicots. This permitted us to elucidate their ecological role and to propose new herbicide models based on their structures. The best phytotoxicity results were shown by the degradation chemical 2-aminophenoxazin-3-one (APO) and several 2-deoxy derivatives of natural benzoxazinones, including 4-acetoxy-(2H)-1,4-benzoxazin- 3(4H)-one (ABOA), 4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one (D-DIBOA), and 4-hydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (D-DIMBOA). They showed high inhibitory activity over almost all species growth. The fact that APO is a degradation product from DIBOA with high phytotoxicity and stability makes it possible to assign an important ecological role regarding plant defense mechanisms. 2-Deoxy derivatives of natural benzoxazinones display a wide range of activities that allow proposing them as new leads for natural herbicide models with a 1,4-benzoxazine skeleton.
- Macias, Francisco A.,Marin, David,Oliveros-Bastidas, Alberto,Castellano, Diego,Simonet, Ana M.,Molinillo, Jose M. G.
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p. 538 - 548
(2007/10/03)
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- INHIBITORS OF HISTONE DEACETYLASE
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The invention relates to a series of compounds useful for inhibiting histone deacetylase (HDAC) enzymatic activity. The invention also provides a method for inhibiting histone descetylase in a cell using said compounds as well as a method for treating cell proliferative diseases and conditions using said HDAC inhibitors. Further, the invention provides pharmaceutical compositions comprising the HDAC inhibiting compounds and a pharmaceutically acceptable carrier.
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Page/Page column 129-130
(2010/02/14)
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- A mild deprotection of trichloroethyl carbamates using indium metal
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The trichloroethoxycarbonyl moiety was efficiently removed from carbamates to furnish the corresponding amines using indium metal in good to excellent yields.
- Mineno, Tomoko,Choi, Seoung-Ryoung,Avery, Mitchell A.
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p. 883 - 886
(2007/10/03)
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- Nivel 1,2-Dithiins: Synthesis, Molecular Modeling Studies, and Antifungal Activity
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The first structure-activity study involving the 1,2-dithiin class of compounds (1,2-dithiacyclohexadienes) is herein reported.A series of 3,6-disubstituted 1,2-dithiins was synthesized from dithiins 1d and 1e and evaluated as antifungal agents.A new and versatile synthesis of dithiins 1d and 1e is reported which is amenable to scale-up at the kilogram level.The novelty of the process derives from the use of β-mercaptopropionitrile as the thiophile, relying on a β-elimination strategy and subsequent oxidation to create the 1,2-dithiin ring.Optimal geometries of dithiins 1d, 18i, and 45 and model dithiin 61 were determined by molecular mechanics and Hartree-Fock molecular orbital calculations.Two possible mechanisms of action are presented for the 1,2-dithiin class of compounds to explain their observed antifungal activities against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus.
- Bierer, Donald E.,Dener, Jeffrey M.,Dubenko, Larisa G.,Gerber, R. Eric,Litvak, Joane,et al.
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p. 2628 - 2648
(2007/10/03)
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- Synthesis and protein tyrosine phosphatase inhibitory activity of dephostatin analogs
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We have synthesized derivatives of dephostatin, a protein tyrosine phosphatase (PTPase) inhibitor, to study the structure-activity relationships of this inhibitor. Inactive analogs revealed some insight into structural requirements for PTPase inhibitory activity of dephostatin. Both a nitroso group and phenolic hydroxyl groups were found to be essential for the inhibitory activity. Among the dephostatin derivatives synthesized, one of the regioisomers of dephostatin showed PTPase inhibitory activity equivalent to that of dephostatin, and also had increased stability.
- Watanabe,Takeuchi,Otsuka,Tanaka,Umezawa
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p. 1460 - 1466
(2007/10/03)
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