- Organocatalytic asymmetric friedel-crafts alkylation of indoles with simple α,β-unsaturated ketones
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Figure presented The first general and highly enantioselective organocatalytic Friedel-Crafts alkylation of indoles with simple α,β-unsaturated ketones has been accomplished. Central to these studies has been the identification of a new catalyst amine salt, in which both the cation and the anion are chiral, that exhibits high reactivity and selectivity for iminium ion catalysis.
- Bartoli, Giuseppe,Bosco, Marcella,Carlone, Armando,Pesciaioli, Fabio,Sambri, Letizia,Melchiorre, Paolo
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- A comparison of Wittig and Wittig Horner (wadsworth emmons) reagents in reactions with some α-dicarbonyl compounds
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For the α-dicarbonyl compounds RCOCHO studied where R=H, Me or Ph it was found that the use of Wittig reagents resulted in higher overall yields of the expected products and that with neither type of reagent could the product OCHCH=CHCO2Et from glyoxal be isolated.
- Mawaziny, Sheila,Makky, Sadiah
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- Efficient oxidation-Wittig olefination-Diels-Alder multicomponent reactions of α-hydroxyketones
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α-Hydroxyketones undergo efficient tandem oxidation-Wittig olefination reactions in the presence of an oxidant to produce high yields of γ-ketocrotonate products. On carrying out the oxidation-Wittig olefination reaction in the presence of 2,3-dimethyl-1,3-butadiene, a novel multicomponent reaction sequence provides access to cycloadducts in high yield.
- Harris, Geraint H.,Graham, Andrew E.
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- Revisiting Bromohexitols as a Novel Class of Microenvironment-Activated Prodrugs for Cancer Therapy
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Bromohexitols represent a potent class of DNA-alkylating carbohydrate chemotherapeutics that has been largely ignored over the last decades due to safety concerns. The limited structure?activity relationship data available reveals significant changes in cytotoxicity with even subtle changes in stereochemistry. However, no attempts have been made to improve the therapeutic window by rational drug design or by using a prodrug approach to exploit differences between tumour physiology and healthy tissue, such as acidic extracellular pH and hypoxia. Herein, we report the photochemical synthesis of highly substituted endoperoxides as key precursors for dibromohexitol derivatives and investigate their use as microenvironment-activated prodrugs for targeting cancer cells. One endoperoxide was identified to have a marked increased activity under hypoxic and low pH conditions, indicating that endoperoxides may serve as microenvironment-activated prodrugs.
- Johansson, Henrik,Hussain, Omar,Allison, Simon J.,Robinson, Tony V.,Phillips, Roger M.,Sejer Pedersen, Daniel
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- A Regioselective Synthesis of 8,10-Dideoxycarminomycinone
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A carminomycinone derivative has been synthesised from 5-hydroxyquinizarin and 2-methoxy-5-methyl-4-nitromethyltetrahydrofuran.
- Ashcroft, Allison E.,Sutherland, James K.
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- Copper-Catalyzed N-O Cleavage of α,β-Unsaturated Ketoxime Acetates toward Structurally Diverse Pyridines
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The copper-catalyzed [4 + 2] annulation of α,β-unsaturated ketoxime acetates with 1,3-dicarbonyl compounds for the synthesis of three classes of structurally diverse pyridines has been developed. This method employs 1,3-dicarbonyl compounds as C2 synthons and enables the synthesis of multifunctionalized pyridines with diverse electron-withdrawing groups in moderate to good yields. The mechanistic investigation suggests that the reactions proceed through an ionic pathway.
- Ding, Xiaojuan,Duan, Jindian,Fang, Zheng,Guo, Kai,Li, Zhenjiang,Mao, Yiyang,Rong, Binsen,Xu, Gaochen,Zhang, Lei,Zhu, Ning
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supporting information
p. 2532 - 2542
(2020/03/13)
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- Design, synthesis, and bioevaluation of a novel class of (E)-4-oxo-crotonamide derivatives as potent antituberculosis agents
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A series of novel (E)-4-oxo-2-crotonamide derivatives were designed and synthesized to find potent antituberculosis agents. All the target compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv(MTB). Results reveal that 4-phenyl moiety at part A and short methyl group at part C were found to be favorable. Most of the derivatives displayed promising activity against MTB with MIC ranging from 0.125 to 4 μg/mL. Especially, compound IIIa16 was found to have the best activity with MIC of 0.125 μg/mL against MTB and with MIC in the range of 0.05–0.48 μg/mL against drug-resistant clinical MTB isolates.
- Ren, Jinfeng,Xu, Jian,Zhang, Guoning,Xu, Changliang,Zhao, LiLi,You, XueFu,Wang, Yucheng,Lu, Yu,Yu, Liyan,Wang, Juxian
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p. 539 - 543
(2019/01/09)
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- Enantioselective NHC-catalysed redox [4+2]-hetero-Diels-Alder reactions using α-aroyloxyaldehydes and unsaturated ketoesters
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N-Heterocyclic carbene (NHC)-catalysed redox [4+2]-hetero-Diels-Alder reactions of α-aroyloxyaldehydes with either β,γ-unsaturated α-ketoesters or α,β-unsaturated γ-ketoesters generates substituted syn-dihydropyranones in good yield with excellent enantioselectivity (up to >99:1 er). The product diastereoselectivity is markedly dependent upon the nature of the unsaturated enone substituent. The presence of either electron-neutral or electron-rich aryl substituents gives excellent diastereoselectivity (up to >99:5 dr), while electron-deficient aryl substituents give reduced diastereoselectivity. In these cases, the syn-dihydropyranone products are more susceptible to base-promoted epimerisation at the C(4)-position under the reaction conditions, accounting for the lower diastereoselectivity obtained.
- Taylor, James E.,Davies, Alyn T.,Douglas, James J.,Churchill, Gwydion,Smith, Andrew D.
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p. 355 - 366
(2017/02/15)
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- Substituted 4-oxo-crotonic acid derivatives as a new class of protein kinase B (PknB) inhibitors: synthesis and SAR study
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Protein kinase B (PknB) is an essential serine/threonine protein kinase required for Mycobacterium tuberculosis (M. tb) cell division and cell-wall biosynthesis. A high throughput screen using PknB identified a (E)-4-oxo-crotonic acid inhibitor, named YH-8, which was used as a scaffold for SAR investigations. A significant improvement in enzyme affinity was achieved. The results indicated that the α,β-unsaturated ketone scaffold and “trans-” configuration are essential for the activity against PknB. And compounds with an aryl group, especially with electron-withdrawing substituents on benzene ring, exhibited four fold potency than that of YH-8.
- Xu, Changliang,Bai, Xiaoguang,Xu, Jian,Ren, Jinfeng,Xing, Yun,Li, Ziqiang,Wang, Juxian,Shi, Jingjing,Yu, Liyan,Wang, Yucheng
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p. 4763 - 4775
(2017/02/05)
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- Synthesis of pyrrolidine-3-carboxylic acid derivatives: Via asymmetric Michael addition reactions of carboxylate-substituted enones
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To concisely synthesize highly enantiomerically enriched 5-alkyl-substituted pyrrolidine-3-carboxylic acids, organocatalytic enantioselective Michael addition reactions of 4-alkyl-substituted 4-oxo-2-enoates with nitroalkanes have been developed. Using the developed reaction method, 5-methylpyrrolidine-3-carboxylic acid with 97% ee was obtained in two steps.
- Yin, Feng,Garifullina, Ainash,Tanaka, Fujie
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supporting information
p. 6089 - 6092
(2017/08/02)
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- Convergent Synthesis of Diverse Nitrogen Heterocycles via Rh(III)-Catalyzed C-H Conjugate Addition/Cyclization Reactions
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The development of Rh(III)-catalyzed C-H conjugate addition/cyclization reactions that provide access to synthetically useful fused bi- and tricyclic nitrogen heterocycles is reported. A broad scope of C-H functionalization substrates and electrophilic olefin coupling partners is effective, and depending on the nature of the directing group, cyclic imide, amide, or heteroaromatic products are obtained. An efficient synthesis of a pyrrolophenanthridine alkaloid natural product, oxoassoanine, highlights the utility of this method.
- Weinstein, Adam B.,Ellman, Jonathan A.
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supporting information
p. 3294 - 3297
(2016/07/13)
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- Acylammonium salts as dienophiles in diels-alder/lactonization organocascades
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α,I?-Unsaturated acylammonium salts, generated in situ from commodity acid chlorides and a chiral isothiourea organocatalyst, comprise a new and versatile family of chiral dienophiles for the venerable Diels-Alder (DA) cycloaddition. Their reactivity is unveiled through a highly diastereo- and enantioselective Diels-Alder/lactonization organocascade that generates cis- and trans-fused bicyclic I?- and I??-lactones bearing up to four contiguous stereocenters. Moreover, the first examples of DA-initiated, stereodivergent organocascades are described delivering complex scaffolds found in bioactive compounds. The origins of stereoselectivity are rationalized through computational studies. In addition, the utility of this methodology is demonstrated through a concise approach to the core structure of glaciolide and formal syntheses of fraxinellone, trisporic acids, and trisporols.
- Abbasov, Mikail E.,Hudson, Brandi M.,Tantillo, Dean J.,Romo, Daniel
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supporting information
p. 4492 - 4495
(2014/04/17)
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- Enantioselective conjugate addition of aliphatic thiols to divergently activated electron poor alkenes and dienes
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Divergently activated double bonds in electron poor 4-oxo-butenoates and (2E,4E)-6-oxo-2,4-dienoates underwent stereoselective and regioselective addition of mercaptans catalyzed by simple Cinchona alkaloids. Application of quinine and quinidine afforded both enantiomers of the 1,4-adducts with respect to the ketone carbonyl group in ees of up to 80%. Single recrystallization of some adducts resulted in further enrichment of up to 99%ee.
- Kowalczyk, Rafa?,Wierzba, Aleksandra J.,Boratyński, Przemys?aw J.,Ba?kowicz, Julia
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supporting information
p. 5834 - 5842
(2015/03/30)
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- Design and synthesis of potent and selective P2X3 receptor antagonists derived from PPADS as potential pain modulators
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Pyridoxalphosphate-6-azophenyl-2′,4′-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X3 receptor antagonists as potential antinociceptive agents. Based on
- Cho, Joong-Heui,Jung, Kwan-Young,Jung, Younghwan,Kim, Min Hye,Ko, Hyojin,Park, Chul-Seung,Kim, Yong-Chul
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p. 811 - 830
(2013/12/04)
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- NOVEL PYRIDINE CARBOXYLIC ACID BASED COMPOUND USED AS A P2X1 AND P2X3 RECEPTOR ANTAGONIST, A PRODUCTION METHOD FOR THE SAME AND A COMPOSITION COMPRISING THE SAME
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Provided are a novel pyridine carboxylic acid based compound used as a P2X1 and P2X3 receptor antagonist, a production method for the same and a composition comprising the same. The compound according to the present invention is a powerful antagonist of P2X1 and P2X3 receptors, and hence can be used as a drug for treating or preventing diseases involving neurological pain or chronic inflammatory diseases which are diseases caused by P2X1 and P2X3 receptor activity.
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Paragraph 0114; 0115
(2013/03/26)
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- Direct access to β-oxodiazo compounds by copper(II)-catalyzed oxidative rearrangement of stabilized vinyl diazo derivatives
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The copper(II)-catalyzed reaction of alkenyldiazo compounds with iodosylbenzene leading to β-oxodiazo derivatives is reported. This process occurs via an unprecedented 1,2-shift of the diazoacetate function. A selection of the synthetic applications of a
- Barluenga, Jose,Lonzi, Giacomo,Riesgo, Lorena,Tomas, Miguel,Lopez, Luis A.
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p. 18138 - 18141
(2011/12/21)
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- A new approach to the synthesis of N-alkylated 2-substituted azetidin-3-ones
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We report a one-pot methodology for the synthesis of N-alkylated 2-substituted azetidin-3-ones based on a tandem nucleophilic substitution followed by intramolecular Michael reaction of primary amines with alkyl 5-bromo-4-oxopent-2-enoates, obtained in tu
- Gerard, Stephane,Raoul, Marion,Sapi, Janos
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p. 2440 - 2445
(2007/10/03)
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- Zinc carbenoid-mediated chain extension: Preparation of α,β-unsaturated-γ-keto esters and amides
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An efficient one-pot preparation of α,β-unsaturated-ω-keto esters and amides has been developed. A zinc carbenoid-mediated chain extension of a β-dicarbonyl substrate provides access to an intermediate zinc enolate, which is treated sequentially with a halogen and amine base. This method has been applied to a variety of ester and amide starting materials, as well as to amino acid-derived substrates and to a formal synthesis of (R,R)-(-)-pyrenophorin.
- Ronsheim, Matthew D.,Zercher, Charles K.
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p. 4535 - 4538
(2007/10/03)
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- The in situ oxidation-Wittig reaction of α-hydroxyketones
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In situ oxidation-Wittig methodology has been applied to α-hydroxyketones avoiding the problems normally associated with α-ketoaldehydes; the procedure is practically simple, and in many cases gives high yields of the product γ-ketocrotonates; the procedu
- Runcie, Karen A.,Taylor, Richard J. K.
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p. 974 - 975
(2007/10/03)
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- Synthesis of analogues of 5-aminolaevulinic acid and inhibition of 5-aminolaevulinic acid dehydratase
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Syntheses are described of several analogues of 5-aminolaevulinic acid (ALA), which are potential inhibitors of ALA dehydratase (porphobilinogen synthase), an early enzyme of tetrapyrrole biosynthesis.Most of the analogues are relatively weak competitive inhibitors of the enzyme from Bacillus subtilis or irreversible inhibitors due to multiple alkylation of the enzyme but the 3-oxa and 3-thia analogues are potent mechanism-based inhibitors which inactive, by acylation of a nucleophilic residue, probably the active-site lysine residue.The kinetics of the inactivation by 3-thiaALA have implications for the mechanism of the enzymic reaction.
- Appleton, Diana,Duguid, A. Bruce,Lee, Sung-Koo,Ha, Young-Jin,Ha, Hyun-Joon,Leeper, Finian J.
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- Lithiated 3-Tosylpropanal and 4-Tosyl-2-butanone Dimethyl Acetals as β-Acylvinyl Anion Equivalents for the Synthesis of Unsaturated 1,4-Dicarbonyl Compound and α,β-Butenolides
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The lithiation of 1,1-dimethoxy-3-tosyllpropane (7a) and 2,2-dimethoxy-4-tosylbutane (7b) followed by reaction with acyl chlorides affords, after p-toluenesulfinic acid elimination, ene-1,4-dicarbonyl compounds in a stereoselective manner.In the case of compound 7a, derived from acrolein, sequential monolithiation and reaction with carbonyl compounds give cyclic acetals, which after oxidation and elimination of p-toluenesulfinic acid are transformed into α,β-butenolides.
- Bonete, Pedro,Najera, Carmen
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p. 2763 - 2776
(2007/10/02)
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- An Intramolecular Diels-Alder Approach to Phorbols: Introduction of an Oxygenated Diene Using a Palladium Catalysed Coupling
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A synthesis of a carbotricycle related to the phorbol skeleton has been achieved in five steps hinging upon an unusual intramolecular Diels-Alder reaction; a usefully oxygenated diene subunit is introduced by a palladium catalysed coupling.
- Page, Philip C. Bulman,Jennens, David C.
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p. 2587 - 2589
(2007/10/02)
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- SULFONE MEDIATED RUPE AND RAPHAEL REARRANGEMENTS
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Base-catalysed addition of methanol to propargylic sulfones selectively gave β-ketosulfones whereas mercuric salts catalysed additions gave γ-ketosulfones.The latter process has been used to prepare one half of pyrenophorine.
- Barre, V.,Massias, F.,Uguen, D.
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p. 7389 - 7392
(2007/10/02)
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- A CONVENIENT SYNTHESIS OF γ-OXO-ACRYLATES
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Ethyl 2,4-dioxoalkanoates react chemoselectively with pyrrolidine acetate at the more electrophilic C-2 carbonyl, producing enaminone esters which on reduction with NaCNBH3 followed by pyrrolidine elimination, were transformed into γ-oxo-acrylates.
- Manfredini, S.,Simoni, D.,Zanirato, V.,Casolari, A.
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p. 3997 - 4000
(2007/10/02)
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- A STRAIGHTFORWARD SYNTHESIS OF PYRENOPHORIN
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A very simple method to prepare 4-oxo-2 alkenoates and an application to the synthesis of a natural fungicidal, pyrenophorin, 1, are described.
- Breuilles, P.,Uguen, D.
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p. 5759 - 5762
(2007/10/02)
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