- Enantioselective total synthesis of (+)-scuteflorin A using organocatalytic asymmetric epoxidation
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We report the first enantioselective total synthesis of (+)-scuteflorin A in 14% overall yield, employing a chiral iminium salt to effect an organocatalytic asymmetric epoxidation of xanthyletin in >99% ee as the key step.
- Bartlett, Christopher J.,Day, David P.,Chan, Yohan,Allin, Steven M.,McKenzie, Michael J.,Slawin, Alexandra M. Z.,Bulman Page, Philip C.
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Read Online
- Masked Amino Trimethyl Lock (H2N-TML) Systems: New Molecular Entities for the Development of Turn-On Fluorophores and Their Application in Hydrogen Sulfide (H2S) Imaging in Human Cells
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Masked trimethyl lock (TML) systems as molecular moieties enabling the bioresponsive release of compounds or dyes in a controlled temporal and spatial manner have been widely applied for the development of drug conjugates, prodrugs or molecular imaging tools. Herein, we report the development of a novel amino trimethyl lock (H2N-TML) system as an auto-immolative molecular entity for the release of fluorophores. We designed Cou-TML-N3 and MURh-TML-N3, two azide-masked turn-on fluorophores. The latter was demonstrated to selectively release fluorescent MURh in the presence of physiological concentrations of the redox-signaling molecule H2S in vitro and was successfully applied to image H2S in human cells.
- Jimidar, Claire Cheyenne,Grunenberg, J?rg,Karge, Bianka,Fuchs, Hazel Leanne Sarah,Br?nstrup, Mark,Klahn, Philipp
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supporting information
(2021/11/10)
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- Synthesis of sorbicillinoid analogues with anti-inflammation activities
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Recently, we demonstrated potential anti-inflammatory effects of sorbicillinoids isolated from marine fungi. Here, we report the synthesis of a series of new sorbicillinoid analogues and assessed their anti-inflammatory activities. Our results reveal that side chain substitution with (E)-2-butenoyl, (E)-3-(4-fluorophenyl)-2-propenoyl, and (E)-3-(3,4,5-trimethoxyphenyl)-2-propenoyl significantly enhanced the inhibitory effects of the derivatives on nitric oxide (NO) production and inducible NO synthesis (iNOS) expression stimulated by lipopolysaccharides (LPS) in mouse macrophage. Further chemical derivatization shows that the monomethylresorcinol skeleton worked better than the dimethylresorcinol skeleton in inhibiting LPS-induced inflammatory response in cultured cells. Among the 29 synthesized sorbicillinoid analogues, compounds 4b and 12b exhibited the strongest anti-inflammatory activities, holding the promise of being developed into lead compounds that can be explored as potent anti-inflammation agents.
- Ding, Wenjuan,Li, Xiaosan,Tang, Jinshan,Tian, Danmei,Wang, Fangfang,Xu, Zhipeng,Zhang, Meng,Zhang, Youwei
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- Synthesis of Succinimides via Intramolecular Alder-Ene Reaction of 1,6-Enynes
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A novel and convenient method has been developed for the facile synthesis of functionalized succinimide derivatives via intramolecular Alder-ene reaction of 1,6-enynes. This reaction features mild and metal-free reaction conditions, which offers a green and efficient entry to synthetically important succinimide scaffolds. Preliminary mechanistic studies suggest that a diradical intermediate might be involved in this transformation.
- Chen, Xia,Lu, Yuling,Guan, Zhenhua,Gu, Lianghu,Chen, Chunmei,Zhu, Hucheng,Luo, Zengwei,Zhang, Yonghui
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supporting information
p. 3173 - 3178
(2021/05/05)
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- Design, synthesis and 3D-QSAR analysis of novel thiopyranopyrimidine derivatives as potential antitumor agents inhibiting A549 and Hela cancer cells
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Four series of thiopyranopyrimidine AZD9291 derivatives containing acrylamide structure were designed, synthesized and evaluated for their antiproliferative activity against A549 and Hela cancer cells. Most of the compounds exhibited excellent antiproliferative activity against A549 cells. Moreover, the compounds with indole ring fluorine substituted exhibited better antiproliferative activity against Hela cells. The most promising compound 23g exhibited excellent enzymatic inhibitory activity and selectivity for EGFRL858R/T790M double mutations. The IC50 value against EGFRL858R/T790M kinase was 16 nM. The compound 23g inhibits selectively against the mutated form of EGFR, with the selectivity more than 125-fold. Furthermore, compound 23g also inhibited A549 cells, Hela cells and H1975 cells proliferation at a low concentration, and the IC50 values were 0.057 μM, 0.104 μM and 0.916 μM, respectively. To further investigate the QSARs of thiopyranopyrimidine derivatives, the CoMFA (q [2] = 0.765, r2 = 0.965) and CoMSIA (q [2] = 0.875, r2 = 0.956) models on Hela cancer cells were established. The generated 3D-QSAR model was validated to be reliable and can be used for further design and optimization of novel and selective EGFR inhibitors.
- Zhao, Bingbing,Zhao, Chengwu,Hu, Xiaohan,Xu, Shan,Lan, Zhou,Guo, Yuping,Yang, Zunhua,Zhu, Wufu,Zheng, Pengwu
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- Design, synthesis and biological evaluation of AZD9291 derivatives as selective and potent EGFRL858R/T790M inhibitors
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Third-generation epidermal growth factor receptor (EGFR)L858R/T790M inhibitors are still the main drugs for the treatment of advanced non-small cell lung cancer (NSCLC), and these drugs have achieved remarkable clinical efficacy. However, there are still many patients suffering from drug-resistant mutations and drug side effects caused by NSCLC. In this study, guided by the molecular simulation, we applied a structure-based drug design strategy (SBDD) and optimized the structure to obtain a series of potent and selective EGFRL858R/T790M inhibitors. The most potent compound 18e demonstrated excellent kinase inhibitory activity and selectivity for EGFRL858R/T790M double mutants and the IC50 value reached nanomolar level. The selectivity of 18e against wild-type EGFR was near to 200-fold. In addition, compound 18e also inhibited H1975 cells proliferation at G2/M phase and induced apoptosis at a concentration of 0.25 μM, which makes it more valuable for potential lung cancer research.
- Zhao, Bingbing,Xiao, Zhen,Qi, Jianguo,Luo, Rong,Lan, Zhou,Zhang, Yanzhuo,Hu, Xiaohan,Tang, Qidong,Zheng, Pengwu,Xu, Shan,Zhu, Wufu
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p. 367 - 380
(2018/12/13)
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- Design, synthesis, antiproliferative activity and docking studies of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline as potential EGFR inhibitors
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Eight series of quinazoline derivatives bearing 2,3-dihydro-indole or 1,2,3,4-tetrahydroquinoline were designed, synthesized and evaluated for the IC50 values against three cancer cell lines (A549, MCF-7 and PC-3). Most of the forty nine target compounds showed excellent antiproliferative activity against one or several cancer cell lines. The compound 13a showed the best activity against A549, MCF-7 and PC-3 cancer cell lines, with the IC50 values of 1.09 ± 0.04 μM, 1.34 ± 0.13 μM and 1.23 ± 0.09 μM, respectively. Eight selected compounds were further selected to evaluated for the inhibitory activity against EGFR kinase. Three of them showed equal activity against EGFR kinase to positive control afatinib. AnnexinV-FITC, propidium iodide (PI) double staining and acridine orange single staining results indicated that the compound 13a could induce apoptosis of human lung cancer A549 cells.
- OuYang, Yiqiang,Zou, Wensheng,Peng, Liang,Yang, Zunhua,Tang, Qidong,Chen, Mengzi,Jia, Shuang,Zhang, Hong,Lan, Zhou,Zheng, Pengwu,Zhu, Wufu
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- Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles
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Silicon-containing compounds have been largely ignored in drug design and development, despite their potential to improve not only the potency but also the physicochemical and ADMET (absorption, distribution, metabolism, excretion, toxicity) properties of drug-like candidates because of the unique characteristics of silicon. This deficiency is in large part attributable to a lack of general methods for synthesizing diverse organosilicon structures. Accordingly, a new building block strategy has been developed that diverges from traditional approaches to incorporation of silicon into drug candidates. Flexible, multi-gram-scale syntheses of silicon-containing tetrahydroquinoline and tetrahydroisoquinoline building blocks are described, along with methods by which diversely functionalized silicon-containing nitrogen heterocycles can be rapidly built using common reactions optimized to accommodate the properties of silicon. Furthermore, to better clarify the liabilities and advantages of silicon incorporation, select compounds and their carbon analogues were challenged in ADMET-focused biological studies.
- Barraza, Scott J.,Denmark, Scott E.
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supporting information
p. 6668 - 6684
(2018/06/12)
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- Design and Synthesis of Natural Product Inspired Libraries Based on the Three-Dimensional (3D) Cedrane Scaffold: Toward the Exploration of 3D Biological Space
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A chemoinformatic method was developed to extract nonflat scaffolds embedded in natural products within the Dictionary of Natural Products (DNP). The cedrane scaffold was then chosen as an example of a nonflat scaffold that directs substituents in three-dimensional (3D) space. A cedrane scaffold that has three orthogonal handles to allow generation of 1D, 2D, and 3D libraries was synthesized on a large scale. These libraries would cover more than 50% of the natural diversity of natural products with an embedded cedrane scaffold. Synthesis of three focused natural product-like libraries based on the 3D cedrane scaffold was achieved. A phenotypic assay was used to test the biological profile of synthesized compounds against normal and Parkinson's patient-derived cells. The cytological profiles of the synthesized analogues based on the cedrane scaffold revealed that this 3D scaffold, prevalidated by nature, can interact with biological systems as it displayed various effects against normal and Parkinson's patient-derived cell lines.
- Tajabadi, Fatemeh Mazraati,Pouwer, Rebecca H.,Liu, Miaomiao,Dashti, Yousef,Campitelli, Marc R.,Murtaza, Mariyam,Mellick, George D.,Wood, Stephen A.,Jenkins, Ian D.,Quinn, Ronald J.
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p. 6609 - 6628
(2018/07/25)
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- ISOSAMIDIN ANALOG AND SAMIDIN ANALOG PRODUCTION METHOD
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PROBLEM TO BE SOLVED: To provide a simple method of industrial-scale production of an isosamidin analog or samidin analog. SOLUTION: In the production method, a compound represented by the formula (1) in the figure is 1) senecioylated and 2) acetylated. [X is O or the like; R1 are each independently a C1-3 alkyl group or the like; R2 is H or the like; R3 are each a C1-3 alkyl group; m is an integer from 0 to 2; n is 1 or 2; and the symbol * represents an asymmetric center.] SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0083
(2018/10/19)
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- Hydropyridylation of Olefins by Intramolecular Minisci Reaction
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An unprecedented cheap, mild and easy methodology for an intramolecular Minisci reaction based on a hydrogen atom transfer (HAT) initiated hydrofunctionalization of olefins was developed. The method is suitable for the construction of unusual dihydropyrano-pyridine and 1,2,3,4-tetrahydronaphthiridine structures and, unlike most similar reactions, does not require exclusion of air from the reaction medium.
- Bordi, Samuele,Starr, Jeremy T.
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supporting information
p. 2290 - 2293
(2017/05/12)
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- Intramolecular Nitrofuran Diels-Alder Reactions: Extremely Substituent-Tolerant Cycloadditions via Asynchronous Transition States
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Nitrofurans undergo intramolecular Diels-Alder reactions with tethered electron-poor dienophiles more rapidly and in higher yield than non-nitrated furans. Computational studies indicate that increased stabilization of a partial positive charge on the nitro-substituted carbon in both transition state and product is the driving force for these reactions. Frontier molecular orbital energy differences indicate a switch from normal to inverse electron demand upon nitration. There does not appear to be a contribution from any differences in aromatic stabilization energy between furans and nitrofurans. Calculations show that the nitrofuran reactions proceed via a highly asynchronous transition state allowing easier bond formation between two sterically hindered carbons.
- Cowie, Thomas Y.,Veguillas, Marcos,Rae, Robert L.,Rougé, Mathilde,Zurek, Justyna M.,Prentice, Andrew W.,Paterson, Martin J.,Bebbington, Magnus W. P.
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p. 6656 - 6670
(2017/07/15)
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- Tuning the Reactivity of Functionalized Diallylic Alcohols: Br?nsted versus Lewis Acid Catalysis
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The chemodivergent reactivity of bifunctional, enol thioether-containing diallylic alcohols in acidic medium is disclosed, highlighting the difference between strong Lewis acid and mild Br?nsted acid catalysis. In the presence of bismuth(III) triflate, allylic alcohol activation affords diversely substituted cyclopentenones in a Nazarov-type electrocyclization, whereas activation of the thioenol ether by p-toluenesulfonic acid provides an entry to α-sulfenylated β,γ-unsaturated ketones. Both methods represent a facile access to the corresponding products under mild conditions, using inexpensive and non-toxic catalytic systems.
- Lempenauer, Luisa,Du?ach, Elisabet,Lemière, Gilles
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supporting information
p. 10285 - 10288
(2017/08/07)
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- Pd-Catalyzed α-Selective C-H Functionalization of Olefins: En Route to 4-Imino-β-Lactams
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Pd-catalyzed α-olefinic C-H activation of simple α,β-unsaturated olefins has been developed. 4-imino-β-lactam derivatives were readily synthesized via activation of α-olefinic C-H bonds with excellent cis stereoselectivity. A wide range of heterocycles at the β-position are compatible with this reaction. The product of 4-imino-β-lactam derivatives can be readily converted to 2-aminoquinoline which exists extensively in pharmaceutical drugs and natural products.
- Kong, Wei-Jun,Liu, Yue-Jin,Xu, Hui,Chen, Yan-Qiao,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 2146 - 2149
(2016/03/05)
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- Rhodium(III)-Catalyzed Cascade Cyclization/Electrophilic Amidation for the Synthesis of 3-Amidoindoles and 3-Amidofurans
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A rhodium(III)-catalyzed cascade cyclization/electrophilic amidation using N-pivaloyloxylamides as the electrophilic nitrogen source has been developed. This protocol provides an efficient route for the synthesis of 3-amidoindoles and 3-amidofurans under mild conditions with good functional group tolerance. The synthetic utility of this reaction has been demonstrated through the derivatization of the 3-amidoindoles to several heterocycle-fused indoles.
- Hu, Zhiyong,Tong, Xiaofeng,Liu, Guixia
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supporting information
p. 2058 - 2061
(2016/06/01)
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- Compositions for Treatment of Cystic Fibrosis and Other Chronic Diseases
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The present invention relates to pharmaceutical compositions comprising an inhibitor of epithelial sodium channel activity in combination with at least one ABC Transporter modulator compound of Formula A, Formula B, Formula C, or Formula D. The invention also relates to pharmaceutical formulations thereof, and to methods of using such compositions in the treatment of CFTR mediated diseases, particularly cystic fibrosis using the pharmaceutical combination compositions.
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Paragraph 0627
(2015/09/22)
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- Synthesis of bicyclic guanidines via cascade hydroamination/michael additions of mono- n -acryloylpropargylguanidines
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A cascade silver(I)-catalyzed hydroamination/Michael addition sequence has been developed to deliver highly substituted bicyclic guanidines. This transformation gives rise to geometrically and constitutionally stable ene-guanidines and generates a remote stereocenter with moderate to high diastereoselectivity.
- Kwon, Ki-Hyeok,Serrano, Catherine M.,Koch, Michael,Barrows, Louis R.,Looper, Ryan E.
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supporting information
p. 6048 - 6051
(2015/01/09)
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- Convenient synthesis of various substituted homotaurines from alk-2-enamides
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Various substituted homotaurines (=3-aminopropane-1-sulfonic acids) 6 were readily synthesized in satisfactory to good yields via the Michael addition of thioacetic acid to alk-2-enamides 3 (→4), followed by LiAlH4 reduction (→5) and performic acid oxidation (Scheme 1). The configuration of 'anti'-disubstituted homotaurine 'anti'-6h was deduced from the 3-(acetylthio)alkanamide (=S-(3-amino-1,2-dimethyl-3-oxopropyl) ethanethioate)'anti'-4h formed in the Michael addition, which was identified via the Karplus equation analysis, and confirmed by X-ray diffraction analysis. The current route is an efficient method to synthesize diverse substituted homotaurines, including 1-, 2-, and N-monosubstituted, as well as 1,2-, 1,N-, 2,N-, and N,N-disubstituted homotaurines (Table). Copyright
- Nai, Youfeng,Xu, Jiaxi
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p. 1355 - 1365
(2013/08/23)
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- Antinociceptive effect of extracts and compounds from Hofmeisteria schaffneri
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Ethnopharmacological relevance: Hofmeisteria schaffneri (Asteraceae) is a medicinal plant widely commercialized in the most important Markets of Mexico City for the treatment of gastro-intestinal complaints and skin afflictions. Aim of the study: The main goals of this study were to establish the potential acute toxicity and the antinociceptive activity in animal models of several preparations and compounds from Hofmeisteria schaffneri. Materials and methods: The aqueous and organic extracts as well as the essential oil of Hofmeisteria schaffneri were prepared by infusion, maceration and hydrodistillation, respectively. Investigation of the acute toxicity was accomplished by the Lorke method. The antinociceptive effect was assessed using the writhing and the hot plate tests. Natural compounds were isolated by standard phytochemical procedures. In addition, a few thymol esters were prepared by chemical synthesis. The stability of natural and synthetic esters was qualitatively analyzed by measuring their susceptibility to hydrolysis by pig liver estearase and mouse plasma at 37°C. Results: The LD50 for each preparation tested was higher than 5000mg/kg revealing that they were not toxic to mice after exposure for short space of time. On the other hand, the extracts showed significant antinociceptive effect when tested in the hot plate model. The most active natural product as antinociceptive agent was hofmeisterin III (1) which also was the most stable in the stability study. Its pharmacological effect seems to be partially mediated by an opioid mechanism since naloxone inhibits its action. Using compound 1 as a lead molecule, several synthetic thymol esters were prepared and only compounds 13, 15 and 17 were antinoceptive at the dose of 1mg/kg. Conclusions: The present investigation provided evidence of the efficacy of several preparations of Hofmeisteria schaffneri as antinociceptive agents. The most active preparation was the essential oil which contained large amount of hofmeisterin III (1) and other thymol derivatives. Some novel synthetic analogs of hofmeisterin III with antinociceptive properties were discovered. The nature of the ester chain of these analogs did not have a clear impact on the antinociceptive activity. The phyto-preparations analyzed in this study were not toxic to mice according to the Lorke's test; therefore considering their long term use of the plant they might be secure for human consumption.
- Angeles-Lopez, Guadalupe,Perez-Vasquez, Araceli,Hernandez-Luis, Francisco,Deciga-Campos, Myrna,Bye, Robert,Linares, Edelmira,Mata, Rachel
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experimental part
p. 425 - 432
(2011/11/14)
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- Synthesis of indoles via alkylidenation of acyl hydrazides
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Indoles have been synthesised via alkylidenation of acyl phenylhydrazides using phosphoranes and the Petasis reagent, followed by in situ thermal rearrangement of the product enehydrazines. The Petasis reagent provides an essentially neutral equivalent of the [acid-catalysed] Fischer indole synthesis, but with acyl phenylhydrazides as starting substrates. Alkylidene triphenylphosphoranes convert aroyl phenylhydrazides to indoles, but acyl phenylhydrazides derived from aliphatic carboxylic acids undergo a Brunner reaction to form indolin-2-ones.
- Hisler, Kevin,Commeureuc, Aurélien G.J.,Zhou, Sheng-ze,Murphy, John A.
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supporting information; experimental part
p. 3290 - 3293
(2009/08/17)
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- PROCESS FOR PRODUCING 2-ISOPROPENYL-5-METHYL-4-HEXENE-1-YL- 3-METHYL-2-BUTENOATE
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Provided is a method capable of solving the problems associated with production of LVSA, which is a pheromone produced by female pest mealybugs, and is useful as an agrochemical pest, at an industrial large scale, and producing LVSA in a high yield. Specifically, the present invention provides a production method of 2-isopropenyl-5-methyl-4-hexen-1-yl 3-methyl-2-butenoate, comprising reacting senecioic acid with a halogenating agent to give senecioic acid halide, reacting the obtained senecioic acid halide with 2-isopropenyl-5-methyl-4-hexen-1-ol in the presence of an organic base compound and heat treating the obtained crude 2-isopropenyl-5-methyl-4-hexen-1-yl 3-methyl-2-butenoate in the presence of a basic substance at 50 - 250°C.
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Page/Page column 4
(2009/12/05)
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- γ-Silylated α,ss-unsaturated amides - Preparation by [1,5]-sigmatropic rearrangement and use as masked dienolate equivalents in carbonyl condensations
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The reaction of lithium dienolates derived from N,N-dialkylsenecioamides (1a-1c) with triorganosilyl electrophiles occurs initially at the oxygen atom predominantly, and is followed by an O → C silicon migration to afford the γ-silylated senecioamides (4a-4h). The γ-silylated senecioamide Z-4a undergoes fluoride-ion-mediated condensations with aromatic aldehydes to give kinetic α-(6) and thermodynamic γ-(5) condensation product patterns comparable to lithium dienolates. The TiCl4-mediated reactions with aldehydes gives a-products (6) in a highly syn-selective manner. Possible transitionstate models for the syn-selective condensations are discussed and a chair-like transition state featuring bidentate coordination to titanium (11) is proposed.
- Green, James R.,Alo, Babajide I.,Majewski, Marek,Snieckus, Victor
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experimental part
p. 745 - 759
(2009/12/04)
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- Diastereoselective nickel-catalyzed reductive Aldol cyclizations using diethylzinc as the stoichiometric reductant: Scope and mechanistic insight
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In the presence of diethylzinc as a stoichiometric reductant, Ni(acac) 2 functions as an efficient precatalyst for the reductive aldol cyclization of α,β-unsaturated carbonyl compounds tethered to a ketone electrophile through an amide or an ester linkage. The reactions are tolerant of a wide range of substitution at both α,β-unsaturated carbonyl and ketone components and proceed smoothly to furnish β-hydroxylactams and β-hydroxylactones with generally high diastereoselectivities. A series of experiments, including deuterium-labeling studies, was carried out in an attempt to gain some insight into the possible reaction mechanisms that might be operative.
- Joensuu, Pekka M.,Murray, Gordon J.,Fordyce, Euan A. F.,Luebbers, Thomas,Hon, Wai Lam
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p. 7328 - 7338
(2008/12/22)
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- COMPOSITION COMPRISING DECURSIN DERIVATIVE FOR TREATING AND PREVENTING ATOPIC DERMATITIS
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The present invention relates to the novel decursin derivatives, the preparation thereof and the composition comprising the same. The novel decursin derivatives of the present invention showedpotent inhibiting activity of the release of MCP-1, IL-6 and IL-8 induced by dermite in THP-1 or EoL-1 cell, therefore the compounds can be useful in treating or preventing atopic dermatitis.
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Page/Page column 44
(2008/12/08)
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- Structure activity studies with xenobiotic substrates using carboxylesterases isolated from Arabidopsis thaliana
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Carboxylesterases (CXEs) catalyse the hydrolysis of xenobiotics and natural products radically altering their biological activities. Whereas the substrate selectivity of animal CXEs, such as porcine liver esterase (PLE) have been well studied, the respective enzymes in plants have yet to be defined and their activities determined. Using Arabidopsis thaliana (At) as a source, five representative members of the α/β hydrolase AtCXE family of proteins have been cloned, expressed and the purified recombinant proteins assayed for esterase activity with xenobiotic substrates. Two members, AtCXE5 and AtCXE18 were found to be active carboxylesterases, though AtCXE5 proved to be highly unstable as a soluble protein. AtCXE18 and the previously characterised S-formylglutathione hydrolase from Arabidopsis (AtSFGH) were assayed against a series of esters based on methylumbelliferone in which the acyl moiety was varied with respect to size and conformation. The same series was used to assay crude esterase preparation from Arabidopsis plants and the results compared with those obtained with the commonly used PLE. With straight chain esters, AtCXE18 behaved like PLE, but the Arabidopsis hydrolases proved less tolerant of branched chain acyl components than the mammalian enzyme. While none of the enzyme preparations accurately reflected all the activities determined with crude Arabidopsis protein extracts, the plant enzymes proved more useful than PLE in predicting the hydrolysis of the more sterically constrained esters.
- Cummins, Ian,Landrum, Marie,Steel, Patrick G.,Edwards, Robert
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p. 811 - 818
(2008/03/13)
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- Tandem [2+2] cycloaddition and Cope rearrangement in reactions of cross-conjugated azatrienes with conjugated ketenes: a facile single step synthesis of novel azocinone derivatives
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A facile single step synthesis of novel azocinone derivatives involving tandem [2+2] cycloaddition and Cope rearrangement in the reactions of cross-conjugated azatrienes with vinyl/isopropenyl ketenes supported by theoretical calculations is reported.
- Singh, Parvesh,Bhargava, Gaurav,Mahajan, Mohinder P.
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p. 11267 - 11273
(2007/10/03)
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- Formation of acrylanilides, acrylamides, and amides directly from carboxylic acids using thionyl chloride in dimethylacetamide in the absence of bases
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A general one-pot procedure is described that rapidly converts acrylic acid to anilides upon sequential treatment of the acid in dimethylacetamide (DMAC) with thionyl chloride and stoichiometric amounts of anilines in 88-98% yields, with DMAC offering rate and stability advantages over the use of DMF. The use of DMAC was extended to other organic acids in forming anilides. Benzylamine amides can also be formed using stoichiometric amounts of benzylamine and brought to completion by warming in the absence of additional base. In addition, it was shown that tert-butylamides can be easily formed with the addition of excess tert-butylamine at 20 °C.
- Cvetovich, Raymond J.,DiMichele, Lisa
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p. 944 - 946
(2012/12/23)
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- Tertiary mercaptoketone, and fragrance and flavor composition containing the same
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[PROBLEM TO BE SOLVED]: To provide a new fragrance and flavor element which have high acceptability, excel in odorant, flavor, depth, etc., and can be useful as a flavor seasoning substance for various products effectively, and to provide a fragrance and a flavor composition containing the same. [SOLUTION]: The tertiary mercaptoketone shown by following formula(I): [Wherein, R and R' are the same or different C1-C3 alkyl group; and the total carbon number of R and R' is 3 or 4], the method for producing the compound, and the fragrance and flavor composition containing the compound.
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Page/Page column 12
(2010/02/12)
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- Intramolecular Diels-Alder reactions of optically active allenic ketones: Chirality transfer in the preparation of substituted oxa-bridged octalones
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The intramolecular Diels-Alder reaction of allenic ketones containing a furyl unit (IMDAF) to generate oxatricyclic systems in good yields is described. The alkene dienophiles 1ab give poor yields of the cycloadducts 2ab, presumably due to the facile retro Diels-Alder reaction. However, the analogous allenic dienophile 7 afforded the desired cycloadduct 8 in 91% yield on treatment with dimethylaluminum chloride. When the allene bears an alkyl substituent on the terminal carbon, complete diastereoselectivity is seen in the IMDAF, e.g. cyclization of 14 gave only the cycloadduct 15 in 80% yield presumably due to greater steric hindrance in the transition state II as compared to that in I. Finally we report complete chirality transfer of the stereochemistry of an allene to the carbon framework of the oxatricyclic system. Thus, the optically active allenic ketone 20 afforded only the desired cycloadduct 21 with the correct absolute stereochemistry needed for the synthesis of the arisugacin class of natural products. Copyright
- Jung, Michael E.,Min, Sun-Joon
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p. 10834 - 10835
(2007/10/03)
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- Cu(I)-catalyzed reductive aldol cyclizations: Diastereo- and enantioselective synthesis of β-hydroxylactones
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(Chemical Equation Presented) Copper bisphosphine complexes catalyze the intramolecular reductive aldol reaction of α,β-unsaturated esters with ketones, affording five-and six-membered β-hydroxylactones in high stereoselectivities. Utilization of chiral nonracemic bisphosphines render the cyclizations enantioselective.
- Lam, Hon Wai,Joensuu, Pekka M.
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p. 4225 - 4228
(2007/10/03)
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- Intramolecular [4+3] cycloadditions. Towards a synthesis of widdrol
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Certain substituted alkoxyallylic sulfones were alkylated and treated with Lewis acids to produce vinylthionium ions that underwent intramolecular [4+3] cycloaddition reactions with a tethered furan. Manipulation of the cycloadduct led to the synthesis of widdrol. Other attempts to prepare the cycloadducts were made, but none were exceptionally better than the route using vinylthionium ions as intermediates. Interesting aspects of the alkylation chemistry of phenylthio-substituted alkoxyallylic sulfones are detailed as well.
- Harmata, Michael,Kahraman, Mehmet,Adenu, Gilbert,Barnes, Charles L.
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p. 583 - 618
(2007/10/03)
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- 4-endo-trig cyclization processes using bis(collidine)bromine(i) hexafluorophosphate as reagent: Preparation of 2-oxetanones, 2-azetidinones, and oxetanes
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Reaction in methylene chloride of bis(collidine)bromine(I) hexafluorophosphate with α,β-unsaturated acids and α,β-unsaturated N- sulfonamides was found to lead diastereospecifically to the corresponding 2- oxetanones and 2-azetidinones in moderate yields (23-60%), by an almost unknown 4-endo cyclization. This process allow the synthesis of these interesting classes of products in one step from common substrates. Similarly, the reaction of cinnamic alcohols led, by the same cyclization procedure, to oxetanes (20-36%); the presence of a gem-dimethyl group in α of the alcohol function appeared beneficial.
- Homsi, Fadi,Rousseau, Gerard
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- Synthesis of amides from Glycosmis species: Methylthiopropenoic acid, methylsulfonylpropenoic acid, thiocarbamic acid S-methyl ester, and senecioic acid amides
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Representative samples of several types of naturally occurring amides from south and southeast Asian Glycosmis species were synthesized for proof of structures and for bioactivity testing. With one exception (senecioic acid) all these amides were characterized by sulfur containing acid components (methylthiopropenoic acid, methylsulfonylpropenoic acid, and thiocarbamic acid) in combination with phenethylamine derived amino moieties.
- Hinterberger, Sabine,Hofer, Otmar,Greger, Harald
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p. 487 - 496
(2007/10/03)
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- 2,3-Dihydro-1-benzofuran-5-ols as analogues of α-tocopherol that inhibit in vitro and ex vivo lipid autoxidation and protect mice against central nervous system trauma
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A series of α-tocopherol analogues was synthesized with potential therapeutic value for such pathological conditions as stroke and trauma. A set of criteria such as the inhibition of in vitro lipid peroxidation, superoxyl radical scavenging, and brain penetration, as measured by ex vivo inhibition of lipid peroxidation, was applied to select the most effective compound. 2,3-Dihydro-2,2,4,6,7-pentamethyl-3-[(4-methylpiperazino)methyl]- 1-benzofuran-5-ol dihydrochloride (22) was selected because of its superior antioxidant properties and better brain penetration. This compound also protected mice against the effects of head injury. The criteria thus turned out to be useful for the characterization of a neuroprotective analogue of α-tocopherol.
- Grisar,Bolkenius,Petty,Verne
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p. 453 - 458
(2007/10/02)
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- SYNTHESIS OF 5-ISOPROPENYL/VINYL SUBSTITUTED PYRIMIDINONES VIA CYCLOADDITION REACTIONS OF 1,3-DIAZA-1,3-BUTADIENES WITH ISOPROPENYL/VINYLKETENES AND THEIR FURTHER TRANSFORMATIONS: AND UNUSUAL CYCLOADDITIONS WITH α-NITROSOSTYRENES
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1,3-Diaza-1,3-butadienes (1 and 5) underwent cycloaddition reactions with isopropenyl/vinylketenes (2), acting as 2? components, to result in pyrimidinones (4 and 7).The treatment of 5-isopropenyl substituted pyrimidinones with phosphorus pentasulfide in the presence of sodium carbonate in dry tetrahydrofuran gave pyrimidinones (8).The reactions of nitrosoalkenes with 5-vinyl substituted pyrimidinones resulted in cycloadditions leading to 1,2-oxazines (15), whereas 5-isopropenyl substituted pyrimidinones resulted in unusual cycloaddition reactions yielding the nitrones (14).
- Sharma, Arun K.,Mahajan, Mohinder P.
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p. 787 - 800
(2007/10/02)
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- Stereoselective reduction of β,δ-diketo esters. A novel strategy for the synthesis of artificial HMG-CoA reductase inhibitors
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Condensation of N-methoxy-N-methyl amides with the dianions of acetoacetates gives in good yields β,δ-diketo esters, which are reduced with Et2BOMe-NaBH4 in tetrahydrofuran-methanol highly selectively to give syn-β,δ-dihydroxy esters in one step. Similarly, the β,δ-diketo esters of the Taber's chiral alcohol or its enantiomer respectively are reduced to give syn-β,δ-dihydroxy esters of moderate enantiomeric excess. Higher diastereo- and enantioselectivity were achieved by reduction of the β,δ-diketo esters of the Taber's chiral alcohol or its enantiomer successively with diisobutylalane and with Et2BOMe-NaBH4. The resulting syn-diol esters were hydrolyzed and lactonized to give various types of β-hydroxy-δ-lactones commonly found in artificial HMG-CoA reductase inhibitors.
- Hiyama,Reddy,Minami,Hanamoto
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p. 350 - 363
(2007/10/02)
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- FOTOQUIMICA DE -TOLUIDIDAS DE ACIDOS αβ-INSATURADOS. INFLUENCIA DE LA ADICION DE CARBONATO POTASICO
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Irradiation of the p-toluidides of crotonic and cinnamic acids (2a,c) gives rise predominantly to the cis isomers 5a,c, together with appreciable amounts of 4,6-dimethyl-3,4-dihydro-2-quinolone (6a) in the case of 2a.The corresponding photo-Fries products have not been detected, even when the irradiation is performed in the presence of K2CO3.By contrast, photolysis of the p-toluidides of methylcrotonic and phenylpropiolic acids (2b,d) gives rise to the o-aminophenones 7b,d (in addition to the quinolone 6b from 2b).For these two amides, as well as for acetanilide and benzanilide, the selectivity towards the acyl migration product markedly increases when the irradiation is performed in the presence of K2CO3.Key words: Enamides' photocyclization, photo-Fries, quinolones.
- Barbera, Carmen,Garcia, Hermenegildo,Miranda, Miguel Angel,Primo, Jaime
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- Stereoselectivity and Generality of the Palladium-Catalysed Cyclopropanation of α,β-Unsaturated Carboxylic Acids Derivatized with Oppolzer's Sultam
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A series of α,β-unsaturated carboxylic acids derivatized with camphorsultam 1 a s a chiral auxiliary has been stereoselectively cyclopropanated. the selectivity of the reaction produces cyclopropanated products with the 1R,2R absolute configuration as indicated by the optical rotations as well as by an X-ray structure determineation.The temperature dependence of the reaction was studied with three substrates. the highest stereoselectivity was obtained at temperatures above 25 deg C.Branching at the α- or β-carbons disfavours complete conversion, and electron-withdrawing substituents at these positions seem to prevent the reaction.The auxiliary was removed by using titanium(IV) isopropoxide in benzyl alcohol followed by alkaline hydrolysis of the intermediate ester. the potent 5-HT1A receptor agonist (1R,2S)-2-(2-hydroxyphenyl)-N,N-dipropylcyclopropylamine 13 was synthesized by this method
- Vallaerda, Jerk,Appelberg, Ulf,Csoeregh, Ingeborg,Hacksell, Uli
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p. 461 - 470
(2007/10/02)
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- The effect of Lewis acids on the intramolecular Diels-Alder reaction of the furan diene
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A general method is described for effecting the intramolecular Diels-Alder reaction of the furan diene in which the side arm connecting the diene to the dienophile contains four carbon atoms.The use of 1.1 equivalents of methylaluminum dichloride at -78 deg C for 2-8 h shifts the Diels-Alder equilibrium towards the products and provides the oxatricyclo adducts in good to excellent yield.Catalytic quantities of methylaluminum dichloride (10 molpercent) provided a higher quantity of adduct than excess Lewis acid when the enone was substituted with alkyl groups.The scope was extended to include a precursor containing a five carbon atom side arm, and two examples containing acetylenic dienophiles that were activated by a carbonyl moiety on the side arm.Precursors having a four carbon atom side arm provided only oxatricyclo adducts having the side arm syn to the oxygen bridge.The assignment of the stereochemistry of the oxatricyclo adducts is discussed in detail.
- Rogers, Christine,Keay, Brian A.
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p. 2929 - 2947
(2007/10/02)
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- A New, General Cyclopentenone Synthesis
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A new synthesis of cyclopentenones, involving an Rh(II)-catalyzed, intramolecular carbon-hydrogen insertion of diazomethyl ketones derived from α,β-unsaturated acids, is described.
- Ceccherelli, Paolo,Curini, Massimo,Marcotullio, Maria Carla,Rosati, Ornelio,Wenkert, Ernest
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p. 311 - 315
(2007/10/02)
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- SYNTHESE REGIOSPECIFIQUE D'AMIDO-1 VINYL-2 CYCLOPROPANES A PARTIR DE LITHIENS ALLYLIQUES MONOHALOGENES ET D'AMIDES TERTIAIRES α-ETHYLENIQUIES
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Chloroallyllitium and gem-chloro(methyl)allyllithium readly react, via conjugated addition and cyclisation, with α-ethylenic aliphatic tertiary amides to produce, in a "one-pot" reaction, alkyl-substituted 1-amido-2-vinylcyclopropanes.
- Ongoka, Pascal,Mauze, Bernard,Miginiac, Leone
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p. 131 - 140
(2007/10/02)
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- INTRAMOLECULAR RING CLOSURE OF α,β-UNSATURATED 3-ACYLINDOLES
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A number of unsaturated 3-acylindoles were prepared and annulated ( with HCl or NaCl-AlCl3 ) to 3,4-dihydrocyclopentindol-1(2H)-ones or 1,2,3,9-tetrahydro-4H-carbazol-4-ones depending on the structure of the substrate and/or the reaction conditions.
- Bergman, Jan,Venemalm, Lennart
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p. 3741 - 3744
(2007/10/02)
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- Carbon-Carbon Bond-Forming Reactions of Zinc Homoenolate of Esters. A Novel Three-Carbon Nucleophile with General Synthetic Utility
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In the presence of suitable catalysts and additives, the zinc homoenolate of alkyl propionate and its congeners undergo a variety of carbon-carbon bond-forming reactions, e.g., addition onto carbonyl compounds, allylation, arylation, vinylation, and acylation, to produce diverse kinds of alkanoates and cyclopropane derivatives.The moderately reactive zinc homoenolate exhibited a very high degree of chemoselectivity in these reactions.Me3SiCl has been found to greatly accelerate 1,2- or 1,4-addition and the allylation reaction of the zinc reagent.
- Nakamura, Eiichi,Aoki, Satoshi,Sekiya, Kouichi,Oshino, Hiroji,Kuwajima, Isao
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p. 8056 - 8066
(2007/10/02)
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- Photoreactivity of α-Fluorinated Phenyl Alkyl Ketones
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The photoreactivities of the mono-, di-, and tri-α-fluorinated acetophenones have been compared to that of acetophenone itself.All four ketones have similar triplet excitation energies; the three fluorinated ketones have reduction potentials 0.5-0.7 eV lower than that of acetophenone.Triplet reactivity toward alkylbenzenes keeps increasing with fluorine substitution, Since the rate-determining step becomes charge-transfer complexation as the ketone reduction potential decreases.The primary/tertiary C-H selectivity toward p-cymene increases with the number of fluorines.Triplet reactivity toward cyclopentane also is increased by fluorination but peaks at two fluorines, since the lowest triplet switches from n,?* to ?,?* with two or three fluorines and ?,?*triplets are unreactive in simple hydrogen atom abstraction.In contrast, α-fluorination of valerophenone does not significantly increase the rate of triplet γ-hydrogen abstraction.The inductive effect on reactivity apparently is offset by a conformational effect.Th α-fluorinated phenones give predominantly cyclobuthanols instead of Norrish type II elimination. α-fluoroacetophenone forms predominantly acetophenone and HF when irradiated with 2-propanol, in what appears a short chain process involving electron transfer to ketone followed by fluoride ion loss.Finally, the radical coupling products in these reactions are formed in varying yields, depending on solvent and additives.It is suggested that radical solvation can affect radical coupling rates sufficiently to prevent statistical ratios of cross-coupling and homo-coupling.
- Wagner, Peter J.,Thomas, Michael J.,Puchalski, Allen E.
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p. 7739 - 7744
(2007/10/02)
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- CONDENSATION DES ORGANOMAGNESIENS SUR LES CHLORUSES D'ACIDE DANS LE TETRAHYDROFURANNE A BASSE TEMPERATURE
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The condensation of a Grignard reagents with hindered acid chlorides in THF at low temperature, yields ketones which are generally difficult to obtain and avoids the side reaction caused with a CuCl catalyst.Applied to unsaturated Grignard reagents and acid chlorides, this method also yields unsaturated ketones, such as the Artemisia ketone.
- Dubois, Jacques-Emile,Lion, Claude,Arouisse, Abdelmajid
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p. 1083 - 1088
(2007/10/02)
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- Conformational Analysis of Some Acrylamide Homologues
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UV absorption and 13C NMR spectra of some acrylamide homologues are discussed in terms of their conformations.They usually assume the planar s-cis conformations, but steric effects in N,N-dimethylamides of methacrylic and senecioic acids are shown to force the molecules into non-planar structures.
- Wojcik, Jacek,Szymanski, Slawomir,Witanowski, Michal,Stefaniak, Lech
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p. 613 - 619
(2007/10/02)
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