- Isotope effects, dynamic matching, and solvent dynamics in a Wittig reaction. Betaines as bypassed intermediates
-
The mechanism of the Wittig reaction of anisaldehyde with a stabilized ylide was studied by a combination of 13C kinetic isotope effects, conventional calculations, and molecular dynamics calculations in a cluster of 53 THF molecules. The isoto
- Chen, Zhuo,Nieves-Quinones, Yexenia,Waas, Jack R.,Singleton, Daniel A.
-
-
Read Online
- An efficient Pd@Pro-GO heterogeneous catalyst for the α, β-dehydrogenation of saturated aldehyde and ketones
-
An Efficient Pd@Pro-GO heterogeneous catalyst was developed that can promote the α, β-dehydrogenation of saturated aldehyde and ketones in the yield of 73% ? 92% at mild conditions without extra oxidants and additives. Pd@Pro-GO heterogeneous catalyst was synthesized via two steps: firstly, the Pro-GO was obtained by the esterification reaction between graphene oxide (GO) and N-(tert-Butoxycarbonyl)-L-proline (Boc-Pro-OH), followed by removing the protection group tert-Butoxycarbonyl (Boc), which endowed the proline-functionalized GO with both the lewis acid site (COOH) and the bronsted base site (NH), besides, the pyrrolidine of proline also can form imine with aldehydes to activate these substrates; Second, palladium was dispersed on the proline-functionalized GO (Pro-GO) to obtained heterogeneous catalyst Pd@Pro-GO. Mechanistic studies have shown that the Pd@Pro-GO-catalyzed α,β-dehydrogenation of saturated aldehyde and ketones was realized by an improved heterogeneously catalyzed Saegusa oxidation reaction. Based on the obove characteristics, the Pd@Pro-GO will be widely used in the transition metal catalytic field.
- Pan, Gao-Fei,Wang, Zhe,Chang, Yi-Yuan,Hao, Yue,Wang, Yi-Chen,Xing, Rui-Guang
-
supporting information
(2021/12/30)
-
- Aminium cation-radical catalysed selective hydration of (E)-aryl enynes
-
The hydration of carbon-carbon triple bonds is an important and atom economic synthetic transformation. Herein, we report a mild and selective method for the catalytic Markovnikov hydration of (E)-aryl enynes to the corresponding enones, mediated through the bench-stable aminium salt, tris(4-bromophenyl)ammoniumyl hexachloroantimonate (TBPA). The chemoselective and diastereoselective method proceeds under neutral metal-free conditions, delivering excellent product yields from terminal and internal alkyne units. The synthesis of biologically important (E)-3-styrylisocoumarins, including a formal synthesis of the natural product achlisocoumarin III, demonstrates the utility of this novel transformation.
- Giel, Marie-Claire,Barrow, Andrew S.,Smedley, Christopher J.,Lewis, William,Moses, John E.
-
supporting information
p. 6991 - 6994
(2021/07/21)
-
- Iron-Catalyzed ?±,?-Dehydrogenation of Carbonyl Compounds
-
An iron-catalyzed α,β-dehydrogenation of carbonyl compounds was developed. A broad spectrum of carbonyls or analogues, such as aldehyde, ketone, lactone, lactam, amine, and alcohol, could be converted to their α,β-unsaturated counterparts in a simple one-step reaction with high yields.
- Zhang, Xiao-Wei,Jiang, Guo-Qing,Lei, Shu-Hui,Shan, Xiang-Huan,Qu, Jian-Ping,Kang, Yan-Biao
-
supporting information
p. 1611 - 1615
(2021/03/03)
-
- Olefin Metathesis, p-Cresol, and the Second Generation Grubbs Catalyst: Fitting the Pieces
-
p-Cresol as additive to the Grubbs second generation catalyst (GII) allows the cross-metathesis of acrylates with prop-1-en-1-ylbenzenes under conditions that only give the prop-1-en-1-ylbenzene self-metathesis product in the absence of cresol. NMR and IR spectroscopy, MALDI-TOF MS and XPS supported the formation of a ruthenium benzylidene with hydrogen bonds between p-cresol and the chloride ligands of GII. XPS furthermore confirmed p-cresol to increase the binding energies of the GII Ru 3d5/2, 3d3/2, 3p3/2 and 3p1/2 photoelectron lines, whereas 1H NMR spectroscopy indicated the carbene carbon and hydrogen to be shielded. It is thus postulated that p-cresol allows for more facile interaction between electron-deficient compounds and the ruthenium benzylidene by decreasing the electron density on the metal center and increasing the electron density on the carbene.
- Swart, Marthinus R.,Twigge, Linette,Erasmus, Elizabeth,Marais, Charlene,Bezuidenhoudt, Barend C. B.
-
supporting information
p. 1752 - 1762
(2021/05/06)
-
- Silica Jar-with-Lid as Chemo-Enzymatic Nano-Compartment for Enantioselective Synthesis inside Living Cells
-
Nanodevices, harvesting the power of synthetic catalysts and enzymes to perform enantioselective synthesis inside cell, have never been reported. Here, we synthesized round bottom jar-like silica nanostructures (SiJARs) with a chemo-responsive metal-silic
- Dubbu, Sateesh,Kim, Seonock,Kumar, Amit,Kumari, Nitee,Lee, In Su,Lim, Jongwon
-
supporting information
p. 16337 - 16342
(2021/06/28)
-
- Design, green synthesis, antioxidant activity screening, and evaluation of protective effect on cerebral ischemia reperfusion injury of novel monoenone monocarbonyl curcumin analogs
-
Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure–activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.
- He, Wenfei,Wang, Jingsong,Jin, Qiling,Zhang, Jiafeng,Liu, Yugang,Jin, Zewu,Wang, Hua,Hu, Linya,Zhu, Lu,Shen, Mengya,Huang, Lili,Huang, Shengwei,Li, Wulan,Zhuge, Qichuan,Wu, Jianzhang
-
-
- Pd-catalyzed oxidative Heck-type arylation of vinyl ketones, alkenes, and acrylates with Sb-aryl-tetrahydrodibenz[c,f][1,5]azastibocines
-
The Pd-catalyzed cross-coupling reactions of Sb-aryl-1,5-azastibocines with alkenes are described. The reactions of azastibocines with alkenes such as vinyl ketones, alkenes, and acrylates in the presence of 10 mol% PdCl2 at 80 °C in DMA under aerobic conditions produced Heck adducts in moderate-to-excellent yields. Single-crystal X-ray and NMR analysis revealed that the aryl donors in this reaction, the Sb-aryl-1,5-azastibocines, are hypervalent compounds that display N–Sb intramolecular non-bonding interaction. These are the first examples of Pd-catalyzed Heck-type arylations using heterocyclic hypervalent organoantimony compounds. Although the reactions proceeded efficiently with the azastibocines, they hardly progressed with trivalent and pentavalent triarylantimony reagents.
- Murata, Yuki,Kakusawa, Naoki,Arakawa, Yukako,Hayashi, Yukako,Morinaga, Shun,Ueda, Masaaki,Hyodo, Tadashi,Matsumura, Mio,Yamaguchi, Kentaro,Kurita, Jyoji,Yasuike, Shuji
-
-
- Catalytic Enantioselective Conjugate Addition of Stereodefined Di- and Trisubstituted Alkenylaluminum Compounds to Acyclic Enones
-
Catalytic enantioselective conjugate addition (ECA) reactions with readily accessible and stereochemically defined E-, Z-, di- and trisubstituted alkenyl aluminum compounds are disclosed. Transformations are promoted by various NHC-copper catalysts (NHC=N-heterocyclic carbene), which are derived from enantiomerically pure sulfonate imidazolinium salts. The desired products were obtained in up to 89% yield and >99:1 e.r.; the alkenyl moiety was transferred with complete retention of its stereochemical identity in all instances. The scope and limitations of the approach, key mechanistic attributes, and representative functionalization are presented as well. (Figure presented.).
- McGrath, Kevin P.,Hubbell, Aran K.,Zhou, Yuebiao,Santos, Damián Padín,Torker, Sebastian,Romiti, Filippo,Hoveyda, Amir H.
-
supporting information
p. 370 - 375
(2019/12/24)
-
- Sequential Two-Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases
-
A sequential two-step chemoenzymatic methodology for the stereoselective synthesis of (3E)-4-(het)arylbut-3-en-2-amines in a highly selective manner and under mild reaction conditions is described. The approach consists of oxidation of the corresponding racemic alcohol precursors by the use of a catalytic system made up of the laccase from Trametes versicolor and the oxy-radical TEMPO, followed by the asymmetric reductive bio-transamination of the corresponding ketone intermediates. Optimisation of the oxidation reaction, exhaustive amine transaminase screening for the bio-transaminations and the compatibility of the two enzymatic reactions were studied in depth in search of a design of a compatible sequential cascade. This synthetic strategy was successful and the combinations of enzymes displayed a broad substrate scope, with 16 chiral amines being obtained in moderate to good isolated yields (29–75 %) and with excellent enantiomeric excess values (94 to >99 %). Interestingly, both amine enantiomers can be achieved, depending on the selectivity of the amine transaminase employed in the system.
- Albarrán-Velo, Jesús,Lavandera, Iván,Gotor-Fernández, Vicente
-
p. 200 - 211
(2019/12/03)
-
- One-pot two-step chemoenzymatic deracemization of allylic alcohols using laccases and alcohol dehydrogenases
-
A series of enantioenriched (hetero)aromatic secondary allylic alcohols has been synthesized through deracemization of the corresponding racemic mixtures combining a non-selective chemoenzymatic oxidation (laccase from Trametes versicolor and oxy-radical TEMPO) and a stereoselective biocatalyzed reduction (lyophilized cells of E. coli overexpressing an alcohol dehydrogenase, ADH). Both steps were performed in aqueous medium under very mild reaction conditions. After optimization, a sequential one-pot two-step protocol was set up, obtaining the corresponding chiral alcohols in moderate to high conversions (48–95%) and enantiomeric excess (65->99% ee). Depending on the ADH stereopreference, both antipodes from these valuable chiral synthons could be prepared, even at preparative scale (119?178 mg), in a straightforward manner.
- Albarrán-Velo, Jesús,Gotor-Fernández, Vicente,Lavandera, Iván
-
-
- Tetrahydroquinazoline derivatives and pharmaceutical composition for preventing or treating psoriasis comprising the same
-
The present invention relates to a tetrahydroquinazoline derivative and a pharmaceutical composition for preventing or treating psoriasis containing the same as an active ingredient. The compound provided in one aspect of the present invention has an effe
- -
-
Paragraph 0251-0255
(2020/11/06)
-
- Discovery and Characterization of Pure RhlR Antagonists against Pseudomonas aeruginosa Infections
-
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic human pathogen that forms biofilms and produces virulence factors via quorum sensing (QS). Blocking the QS system in P. aeruginosa is an excellent strategy to reduce biofilm formation and the production of virulence factors. RhlR plays an essential role in the QS system of P. aeruginosa. We synthesized 55 analogues based on the chemical structure of 4-gingerol and evaluated their RhlR inhibitory activities using the cell-based reporter strain assay. Comprehensive structure-activity relationship studies identified the alkynyl ketone 30 as the most potent RhlR antagonist. This compound displayed selective RhlR antagonism over LasR and PqsR, strong inhibition of biofilm formation, and reduced production of virulence factors in P. aeruginosa. Furthermore, the survival rate of Tenebrio molitor larvae treated with 30 in vivo greatly improved. Therefore, compound 30, a pure RhlR antagonist, can be utilized for developing QS-modulating molecules in the control of P. aeruginosa infections.
- Nam, SangJin,Ham, So-Young,Kwon, Hongmok,Kim, Han-Shin,Moon, Suhyun,Lee, Jeong-Hoon,Lim, Taehyeong,Son, Sang-Hyun,Park, Hee-Deung,Byun, Youngjoo
-
supporting information
p. 8388 - 8407
(2020/09/21)
-
- A Heck reaction/photochemical alkene isomerization sequence to prepare functionalized quinolines
-
A route to prepare functionalized quinolines based on a Heck reaction/UV-induced alkene isomerization sequence is described. The method allows for the preparation of quinolines under mild and neutral conditions and has broad functional group tolerance. Acid-sensitive functional groups that would not be tolerated under previous approaches can be included and a one-pot quinoline forming procedure is also reported.
- Donohoe, Timothy J.,Hoff, Oskar,Hoffman, Jack B.,Kelly, Alex,Walker, Johannes C. L.,Werrel, Simon
-
-
- Thermal decarboxylative Nazarov cyclization of cyclic enol carbonates involving chirality transfer
-
Decarboxylative Nazarov cyclization of chiral cyclic enol carbonates proceeded to afford chiral 2-cyclopentenones with excellent chirality transfer under thermal conditions without any catalyst. Interestingly, the thermal decarboxylative Nazarov cyclization furnished the desired product with better chirality transfer than the Lewis acid-catalyzed reaction.
- Kozuma, Akane,Komatsuki, Keiichi,Saito, Kodai,Yamada, Tohru
-
supporting information
p. 60 - 63
(2019/12/12)
-
- Saccharomonosporine A inspiration; synthesis of potent analogues as potential PIM kinase inhibitors
-
Saccharomonosporine A was recently reported as a natural anti-cancer agent working through inhibition of a Proviral integration site for Moloney murine leukemia virus-1 (PIM-1) kinase. Structural bioisosteres of this natural product were synthesized and t
- Abdel-Rahman, Hamdy M.,Abdelmohsen, Usama Ramadan,Aboulmagd, Asmaa M.,Hassan, Hossam M.,Sayed, Ahmed M.
-
p. 6752 - 6762
(2020/03/03)
-
- First aromatic amine organocatalysed activation of α,β-unsaturated ketones
-
This work provides an unprecedented example of a chiral aromatic amine used to activate α,β-unsaturated ketones in asymmetric aminocatalysis. Chiral aromatic diamine VII has been efficiently employed, as a proof of concept, in the Michael addition reaction between benzylideneacetones (1a-f) and coumarins (2a-d). The reaction gives rise to warfarin derivatives 3 with promising results using this family of catalysts for the first time. The additional studies performed supported the bifunctional mode of activation of the chiral catalyst VII and the covalent nature of the interactions between the catalyst VII and benzylideneacetones 1.
- Sonsona, Isaac G.,Marqués-López, Eugenia,Gimeno, M. Concepción,Herrera, Raquel P.
-
supporting information
p. 12233 - 12240
(2019/08/12)
-
- Enantioselective Reduction of α,β-Unsaturated Ketones and Aryl Ketones by Perakine Reductase
-
This report describes the enantioselective reduction of structurally diverse α,β-unsaturated ketones and aryl ketones by perakine reductase (PR) from Rauvolfia. This enzymatic reduction produces α-chiral allylic and aryl alcohols with excellent enantioselectivity and most of the products in satisfactory yields. Furthermore, the work demonstrates 1 mmol scale reactions for product delivery without any detrimental effect on yield and enantioselectivity. The catalytic mechanism, determined by 3D-structure-based modeling of PR and ligand complexes, is also described.
- Cai, Sheng,Shao, Nana,Chen, Yuanyuan,Li, Anbang,Pan, Jie,Zhu, Huajian,Zou, Hongbin,Zeng, Su,Sun, Lianli,Zhao, Jinhao
-
supporting information
p. 4411 - 4414
(2019/05/22)
-
- Iron(III)/O2-Mediated Regioselective Oxidative Cleavage of 1-Arylbutadienes to Cinnamaldehydes
-
A simple, efficient, and environmentally benevolent regioselective oxidative cleavage of 1-arylbutadienes to cinnamaldehydes mediated by iron(III) sulfate/O2 has been developed. The reaction offered good yields and excellent regioselectivity and showed good functional group tolerance (31 examples). The method is important, as few reports with limited substrate scope are available for such excellent oxidative cleavage of conjugated dienes.
- Bhowmik, Amit,Fernandes, Rodney A.
-
supporting information
p. 9203 - 9207
(2019/11/14)
-
- A Broad-Spectrum Synthesis of Tetravinylethylenes
-
The first general synthesis of compounds of the tetravinylethylene (TVE) family is reported. Ramirez-type dibromo-olefination of readily accessible penta-1,4-dien-3-ones generates 3,3-dibromo[3]dendralenes, which undergo twofold Negishi, Suzuki–Miyaura or Mizoroki–Heck reactions with a wide variety of olefinic coupling partners. This route delivers a broad range of unsymmetrically substituted tetravinylethylenes with up to three different alkenyl substituents attached to the central C=C bond. The extensive scope of the approach is demonstrated by the preparation of the first higher order oligo-alkenic through-conjugated/cross-conjugated hybrid compounds. An unsymmetrically substituted TVE is shown to undergo a domino electrocyclization–cycloaddition with high site-selectivity and diastereoselectivity, thereby demonstrating the substantial synthetic potential of substituted TVEs for controlled, rapid structural complexity generation.
- Horvath, Kelsey L.,Newton, Christopher G.,Roper, Kimberley A.,Ward, Jas S.,Sherburn, Michael S.
-
supporting information
p. 4072 - 4076
(2019/03/22)
-
- Synthesis of Enones and Enals via Dehydrogenation of Saturated Ketones and Aldehydes
-
A general, efficient and economic palladium-catalyzed dehydrogenation to form enones or enals has been developed. The approach possesses extremely broad substrate scope including various linear or cyclic saturated ketones and aldehydes. The protocol is ligand-free, and molecular oxygen is used as the sole clean oxidant in the reaction. Due to mild reaction conditions, good functional group compatibility, and versatile utilities of enones and enals, the method can be applied in the late-stage synthesis of natural products, pharmaceuticals and fine chemicals. (Figure presented.).
- Pan, Gao-Fei,Zhu, Xue-Qing,Guo, Rui-Li,Gao, Ya-Ru,Wang, Yong-Qiang
-
p. 4774 - 4783
(2018/11/10)
-
- Synthesis and biological evaluation of curcumin inspired imidazo[1,2-a]pyridine analogues as tubulin polymerization inhibitors
-
With an aim to develop new curcumin inspired analogues as potent anticancer agents, we synthesized a series of (1E,4E)-1-phenyl-5-(3-phenylimidazo[1,2-a]pyridin-2-yl)penta-1,4-dien-3-ones (12a–t) as tubulin polymerization inhibitors. An initial screening was carried out to evaluate their cytotoxic potential on a panel of six cancer cell lines namely, cervical (HeLa), gastric (HGC-27), lung (NCI-H460), prostate (DU-145 and PC-3) and breast (4T1), using MTT assay. Among the compounds tested, compounds 12e, 12r and 12t showed potent growth inhibition and 12t {(1E,4E)-1-(3-(3,4-difluorophenyl)imidazo[1,2-a]pyridin-2-yl)-5-(2,4,6-trimethoxyphenyl)penta-1,4-dien-3-one} being the most active member of the series inhibited the growth of all the tested cell lines with IC50 values varying from 1.7 – 2.97 μM. Moreover, 12t showed promising cytotoxicity on PC-3, HGC-27 and HeLa cell lines with IC50 values of 2.11 ± 0.27 μM, 2.21 ± 0.25 μM and 2.53 ± 0.01 μM respectively. The results from aqueous solubility test showed that compounds 12e and 12t have 1.7 and 2.8 times more aqueous solubility than curcumin. Interestingly, the most active compound 12t was found to be nearly 2 times more selective on PC-3 cells as well as safe on normal human prostate (RWPE-1) cells. In addition, compound 12t efficiently inhibited tubulin polymerization with IC50 value of 8.44 ± 0.13 μM and molecular modelling studies disclosed that 12t binds at the colchicine binding site of the tubulin. Cell cycle analysis revealed that 12t arrests PC-3 cells in G2/M phase in a dose dependant manner. Further, treatment of PC-3 cells with 12t showed typical apoptotic morphology, also led to the impairment of mitochondrial membrane potential (DΨm) and increased levels of reactive oxygen species (ROS). Altogether, the results from acridine orange/ethidium bromide (AO-EB) and DAPI staining studies, annexin V-FITC/propidium iodide staining assay, analysis of mitochondrial membrane potential (DΨm) and reactive oxygen species (ROS) levels undoubtedly demonstrated the induction of apoptosis in PC-3 cells by compound 12t.
- Ramya, P.V. Sri,Guntuku, Lalita,Angapelly, Srinivas,Digwal, Chander Singh,Lakshmi, Uppu Jaya,Sigalapalli, Dilep Kumar,Babu, Bathini Nagendra,Naidu,Kamal, Ahmed
-
p. 216 - 231
(2017/11/27)
-
- Curcumin inspired 2-chloro/phenoxy quinoline analogues: Synthesis and biological evaluation as potential anticancer agents
-
Synthesis of twenty new curcumin inspired 2-chloro/phenoxy quinoline derivatives is outlined in this study. The obtained new chemical entities were screened in vitro for their cytotoxic activity towards various tumor cell lines. Of the compounds screened, 6c and 9d exhibited significant activity and the most active analogue 6c displayed promising cytotoxicity against PC-3 (IC50 of 3.12 ± 0.11 μM), DU-145, NCI-H460 and 4 T1 cell lines. Further, 6c and 9d have 2.1 and 1.4 times more aqueous solubility, respectively, than curcumin. Additionally, the promising candidate 6c could induce G2/M cell cycle arrest and apoptosis in PC-3 cells, as determined by AO-EB staining, DAPI staining, analysis of ROS levels as well as annexin binding assay.
- Sri Ramya,Guntuku, Lalita,Angapelly, Srinivas,Karri, Shailaja,Digwal, Chander Singh,Babu, Bathini Nagendra,Naidu,Kamal, Ahmed
-
supporting information
p. 892 - 898
(2018/02/13)
-
- New selective cyclooxygenase-2 inhibitors from cyclocoumarol: Synthesis, characterization, biological evaluation and molecular modeling
-
In this work, a serie of cyclocoumarol derivatives was designed, synthesized, characterized and studied for their potentialities as selective inhibitors of COX-2. All target compounds have been screened for their anti-inflammatory activity by the assay of PGE2 production. Among them, compound 5d exhibited the most potent inhibitory activity with a PGE2 inhibition compared to NS-398 (79% and 88% respectively) and showed non-inhibitory activity towards the COX-1 enzyme. Docking studies revealed the capacity of this compound to occupy the selective COX-2 cavity establishing additional hydrogen bonds between the oxygen of the methoxy group and the His90 and Arg513 of the binding site of the enzyme.
- Rayar, Anita Marie,Lagarde, Nathalie,Martin, Frederique,Blanchard, Florent,Liagre, Bertrand,Ferroud, Clotilde,Zagury, Jean-Fran?ois,Montes, Matthieu,Sylla-Iyarreta Veitía, Maité
-
p. 577 - 587
(2018/02/10)
-
- A Mild Procedure for Enone Preparation Catalysed by Bovine Serum Albumin in a Green and Easily Available Medium
-
Abstract: A simple and mild procedure to obtain α,β-unsaturated ketones from acetone and a set of benzaldehydes is described. The approach applies bovine serum albumin (BSA) catalysis and water or ethanol, this mild reaction medium contrasting with the strong reaction conditions of the classic aldol condensation. Except for the assayed nitrobenzaldehydes, high enone yields (88–97%) were attained. In addition to its mildness, further advantages of this procedure are the use of a green catalyst exhibiting an efficient reuse and the use of eco-friendly and cheap solvents. In order to gain a deeper understanding of the involved catalytic mechanism, computational experiments on BSA structural analysis and molecular docking were carried out.
- Ardanaz, Sebastián M.,Velez Rueda, Ana J.,Parisi, Gustavo,Iribarren, Adolfo M.,Iglesias, Luis E.
-
p. 1750 - 1757
(2018/04/24)
-
- Poly(N-isopropylacrylamide-co-l-proline)-catalyzed Claisen-Schmidt and Knoevenagel condensations: Unexpected enhanced catalytic activity of the polymer catalyst
-
The polymer catalyst is more effective than the corresponding monomer catalyst? Yes! The proline-modified polymer, poly(N-isopropylacrylamide-co-l-proline), was unexpectedly found to be more effective than the corresponding monomer l-proline catalyst in Claisen-Schmidt and Knoevenagel condensation reactions. 1H NMR, GC analysis and control reactions revealed that this abnormal phenomenon might be attributed to an enhanced concentration of the reactant on the surface of the polymer catalyst, which might be due to adsorption of the reactants to the polymer through hydrogen-bonding of the proline moiety with the reactants. This new polymer catalyst was so robust that it could be reused at least 10 times without deactivation. The polymer-catalyzed method was rather tolerant of substrates bearing sensitive groups that are usually incompatible with conventional acid- or base-catalyzed methods, reducing the protection-deprotection steps of the substrates.
- Zhang, Hao,Han, Mengting,Chen, Tian,Xu, Lin,Yu, Lei
-
p. 48214 - 48221
(2017/11/03)
-
- Synthesis and biological evaluation of curcumin inspired indole analogues as tubulin polymerization inhibitors
-
In our endeavour towards the development of potent cytotoxic agents, a series of some new curcumin inspired indole analogues, in which indole and phenyl moieties are linked on either sides of 1,5-diaryl-1,4-pentadien-3-one system have been synthesized and characterized by spectral data. All the newly synthesized analogues were tested for their cytotoxic potential against a panel of eight cancer cell lines namely, lung (A549), breast (MDA-MB-231, BT549 and 4T1), prostate (PC-3, DU145), gastric (HGC-27) and cervical (HeLa). Notably, among all the compounds tested, compounds 11c, 11d and 11f showed potent growth inhibition on PC-3 and BT549 with IC50values in the range of 3.12–6.34?μM and 4.69–8.72?μM respectively. The most active compound (11c) was also tested on RWPE-1 (normal prostate) cells and was found to be safe compared to the PC-3?cells. In tubulin polymerization assay, compounds 11c and 11f effectively inhibited microtubule assembly with IC50values of 10.21?±?0.10 and 8.83?±?0.06?μM respectively. The results from molecular modelling studies revealed that these compounds bind at the colchicine binding site of the tubulin. Moreover, DAPI and acridine orange/ethidium bromide staining studies indicated that compounds 11c and 11f can induce apoptosis in PC-3?cells. Further flow-cytometry analysis revealed that compound 11c arrests PC-3?cells in G2/M phase of the cell cycle while compound 11f treatment resulted in moderate increase in the G2/M population. Additionally, the treatment by these compounds led to the impairment of mitochondrial membrane potential (DΨm) in PC-3?cells.
- Sri Ramya,Angapelly, Srinivas,Guntuku, Lalita,Singh Digwal, Chander,Nagendra Babu, Bathini,Naidu,Kamal, Ahmed
-
p. 100 - 114
(2016/12/30)
-
- Stereospecific Decarboxylative Nazarov Cyclization Mediated by Carbon Dioxide for the Preparation of Highly Substituted 2-Cyclopentenones
-
Highly substituted 2-cyclopentenones were stereospecifically and regioselectively constructed with high catalytic efficiency through Lewis-acid catalyzed decarboxylative Nazarov cyclization of the cyclic carbonate derivative, which is prepared by reacting the propargyl alcohol with carbon dioxide in the presence of a silver catalyst. The stereochemistry of the 2-cyclopentenone is strictly controlled by the geometry of the alkene in the starting material. This method is applicable for various substrates.
- Komatsuki, Keiichi,Sadamitsu, Yuta,Sekine, Kohei,Saito, Kodai,Yamada, Tohru
-
supporting information
p. 11594 - 11598
(2017/09/11)
-
- Copper-catalyzed retro-aldol reaction of β-hydroxy ketones or nitriles with aldehydes: Chemo- and stereoselective access to (E)-enones and (E)-acrylonitriles
-
A copper-catalyzed transfer aldol type reaction of β-hydroxy ketones or nitriles with aldehydes is reported, which enables chemo- and stereoselective access to (E)-α,β-unsaturated ketones and (E)-acrylonitriles. A key step of the in situ copper(i)-promoted retro-aldol reaction of β-hydroxy ketones or nitriles is proposed to generate a reactive Cu(i) enolate or cyanomethyl intermediate, which undergoes ensuing aldol condensation with aldehydes to deliver the products. This reaction uses 1.2 mol% Cu(IPr)Cl (IPr denotes 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) as the catalyst in the presence of 6.0 mol% NaOtBu cocatalyst at room temperature or 70 °C. A range of aryl and heteroaryl aldehydes as well as acrylaldehydes are compatible with many useful functional groups being tolerated. Under the mild and weakly basic conditions, competitive Cannizzaro-type reaction of benzaldehydes and side reactions of base-sensitive functional groups can be effectively suppressed, which show synthetic advantages of this reaction compared to classic aldol reactions. The synthetic potential of this reaction is further demonstrated by the one-step synthesis of biologically active quinolines and 1,8-naphthyridine in excellent yields (up to 91%). Finally, a full catalytic cycle for this reaction has been constructed using DFT computational studies in the context of a retro-aldol/aldol two-stage mechanism. A rather flat reaction energy profile is found indicating that both stages are kinetically facile, which is consistent with the mild reaction conditions.
- Zhang, Song-Lin,Deng, Zhu-Qin
-
p. 7282 - 7294
(2016/08/05)
-
- Traceless OH-Directed Wacker Oxidation-Elimination, an Alternative to Wittig Olefination/Aldol Condensation: One-Pot Synthesis of α,β-Unsaturated and Nonconjugated Ketones from Homoallyl Alcohols
-
A new method for one-pot synthesis of β-substituted and β,β-disubstituted α,β-unsaturated methyl ketones from homoallyl alcohols by sequential PdCl2/CrO3-promoted Wacker process followed by an acid-mediated dehydration reaction has been developed. Remarkably, internal homoallyl alcohols delivered regioselectively nonconjugated unsaturated carbonyl compounds under the same protocol. A new starting material-based synthesis of α,β-unsaturated and nonconjugated methyl ketones is demonstrated.
- Bethi, Venkati,Fernandes, Rodney A.
-
p. 8577 - 8584
(2016/09/28)
-
- Iridium(I) N-Heterocyclic Carbene (NHC)/Phosphine Catalysts for Mild and Chemoselective Hydrogenation Processes
-
The directed chemoselective hydrogenation of olefins has been established by using iridium(I) catalysts, which feature a tuned NHC/phosphine ligand combination. This selective reduction process has been demonstrated in a wide array of solvents, including more environmentally acceptable media, also allowing further refinement of hydrogenation selectivity. The directed, chemoselective hydrogenation of olefins has been established by using iridium(I) catalysts, which feature a tuned NHC/phosphine ligand combination. This selective reduction process has been demonstrated in a wide array of solvents, including more environmentally acceptable media, also allowing further refinement of hydrogenation selectivity.
- Kerr, William J.,Mudd, Richard J.,Brown, Jack A.
-
supporting information
p. 4738 - 4742
(2016/04/05)
-
- Novel Benzo[a]quinolizidine Analogs Induce Cancer Cell Death through Paraptosis and Apoptosis
-
Paraptosis is nonapoptotic cell death characterized by massive endoplasmic reticulum (ER)- or mitochondria-derived vacuoles. Induction of paraptosis offers significant advantages for the treatment of chemotherapy-resistant tumors compared with anticancer drugs that rely on apoptosis. Because some natural alkaloids induce paraptotic cell death, a novel series of benzo[a]quinolizidine derivatives were synthesized, and their antiproliferative activity and ability to induce cytoplasmic vacuolation were analyzed. Structural optimization led to the identification of the potent compound 22b, which inhibited cancer cell proliferation in vitro and in vivo and profoundly facilitated paraptosis-like cell death and induced caspase-dependent apoptosis. Further investigation revealed that 22b-mediated vacuolation originated from persistent ER stress and upregulation of LC3B. Paraptosis induced by benzo[a]quinolizidine derivatives thus represents an alternative strategy for cancer chemotherapy.
- Zheng, Hongbo,Dong, Yiwen,Li, Lin,Sun, Bin,Liu, Lei,Yuan, Huiqing,Lou, Hongxiang
-
supporting information
p. 5063 - 5076
(2016/06/13)
-
- N,N,N′,N′-Tetramethylenediamine dioxide (TMEDAO2) facilitates atom economical/open atmosphere Ley-Griffith (TPAP) tandem oxidation-Wittig reactions
-
N,N,N′,N′-Tetramethylethylenediamine dioxide (TMEDAO2) was explored as a more atom economical co-oxidant for the Ley-Griffith oxidation of alcohols to aldehydes. TMEDAO2 was found to selectivity oxidise benzylic and allylic alcohols in comparable yields to that of the standard Ley-Griffith co-oxidant (NMO). Importantly TMEDAO2 facilitated tandem Ley-Griffith-Wittig reactions with stabilised ylides, in good to excellent yields, without the requirement of anhydrous conditions.
- Read, Christopher D. G.,Moore, Peter W.,Williams, Craig M.
-
supporting information
p. 4537 - 4540
(2015/09/15)
-
- Organocatalyzed Asymmetric Conjugate Addition of Heteroaryl and Aryl Trifluoroborates: A Synthetic Strategy for Discoipyrrole D
-
Bis-heteroaryl or bis-aryl stereocenters were formed by an organocatalytic enantioselective conjugate addition using the respective trifluoroborate salts as nucleophiles. Control studies suggested that fluoride dissociation is necessary in the anhydrous conditions. This strategy is applicable to the synthesis of discoipyrrole D, an inhibitor of BR5 fibroblast migration.
- Shih, Jiun-Le,Nguyen, Thien S.,May, Jeremy A.
-
supporting information
p. 9931 - 9935
(2015/08/19)
-
- A promiscuous de Novo retro-aldolase catalyzes asymmetric michael additions via Schiff base intermediates
-
Recent advances in computational design have enabled the development of primitive enzymes for a range of mechanistically distinct reactions. Here we show that the rudimentary active sites of these catalysts can give rise to useful chemical promiscuity. Sp
- Garrabou, Xavier,Beck, Tobias,Hilvert, Donald
-
supporting information
p. 5609 - 5612
(2015/10/12)
-
- Efficient and facile synthesis of novel stable monodeuterium labeled ractopamine
-
A novel synthetic route to stable deuterium labeled ractopamine was disclosed with 6.49% total yield and 97.7% isotopic abundance. Its structure and the isotope-abundance were confirmed according to 1H-NMR and high-resolution mass spectrometry. A novel synthetic route to stable deuterium labeled ractopamine was disclosed with 9 steps, 6.49% total yield and 97.7% isotopic abundance. Its structure and the isotope-abundance were confirmed according to 1H-NMR and high-resolution mass spectrometry.
- Su, Feifei,Wu, Fulong,Tang, He,Wang, Zhonghua,Wu, Fanhong
-
p. 479 - 482
(2016/01/27)
-
- Organoselenium-catalyzed baeyer-villiger oxidation of α,β-unsaturated ketones by hydrogen peroxide to access vinyl esters
-
By carefully screening the organoselenium pre-catalysts and optimizing the reaction conditions, simple dibenzyl diselenide was found to be the best pre-catalyst for Baeyer-Villiger oxidation of (E)-α,β-unsaturated ketones with the green oxidant hydrogen peroxide at room temperature. The organoselenium catalyst used in this reaction could be recycled and reused several times. This new method was suitable not only for methyl unsaturated ketones, but also for alkyl and aryl unsaturated ketones. Therefore, it provided a direct, mild, practical, highly functional group-tolerant process for the chemoselective preparation of the versatile (E)-vinyl esters from the readily available (E)-α,β-unsaturated ketones. A possible mechanism was also proposed to rationalize the activity of the organoselenium catalyst in the presence of hydrogen peroxide in this Baeyer-Villiger oxidation reaction.
- Zhang, Xu,Ye, Jianqing,Yu, Lei,Shi, Xinkang,Zhang, Ming,Xu, Qing,Lautens, Mark
-
supporting information
p. 955 - 960
(2015/03/30)
-
- Design, synthesis and biological evaluation of novel C3-functionalized oxindoles as potential Pim-1 kinase inhibitors
-
A novel series of C3-functionalized oxindoles, 3-(2-oxo-4-phenylbut-3-en-1-ylidene)indolin-2-ones, were designed, synthesized and investigated for inhibition of cell proliferation against different types of human cancer cell lines, including SW620, HeLa and A549. This biological study showed that these compounds containing the scaffolds of indole and aromatic α,β-unsaturated ketone had moderate to significant antitumor activities. Further study suggested that compound 4b, as one of this kind of structure derivative, showed broad-spectrum antitumor activities against MCF-7, PC-3, SKOV-3, U87, SMMC-7721, SY5Y and A875 cancer cell lines. Besides, the results of the inhibition of Pim kinases indicated that compound 4b showed selective and efficient anti-Pim-1 kinase activity (IC50 = 5 μM). Docking simulation, flow cytometry (FCM), and Hoechst 33342 staining assay suggested that the most active compound 4b induced cell death through apoptosis via binding to the active ATP pocket of Pim-1. Moreover, it showed that compound 4b had strong inhibition of tubulin polymerization which may be caused by inhibiting Pim-1. This journal is
- Sun, Hong-Bao,Wang, Xiao-Yan,Li, Guo-Bo,Zhang, Li-Dan,Liu, Jie,Zhao, Li-Feng
-
p. 29456 - 29466
(2015/04/14)
-
- Synthesis of new 4-phenylpyrimidine-2(1H)-thiones and their potency to inhibit COX-1 and COX-2
-
Several new 4-phenylpyrimidine-2(1H)-thiones have been prepared and investigated for their potencies to inhibit COX-1 and COX-2 enzymes, and COX-2 expression in THP-1 cells. Structure-activity-relationships and physicochemical parameters are discussed. Pharmacophore screening and docking studies were carried out for the most active compound.
- Seebacher, Werner,Faist, Johanna,Presser, Armin,Weis, Robert,Saf, Robert,Kaserer, Teresa,Temml, Veronika,Schuster, Daniela,Ortmann, Sabine,Otto, Nadine,Bauer, Rudolf
-
p. 552 - 559
(2015/07/27)
-
- PPh3·HBr-DMSO mediated expedient synthesis of γ-substituted β,γ-unsaturated α-ketomethylthioesters and α-bromo enals: Application to the synthesis of 2-methylsulfanyl-3(2 H)-furanones
-
An efficient chemoselective general procedure for the synthesis of γ-substituted β,γ-unsaturated α-ketomethylthioesters from α,β-unsaturated ketones has been achieved through an unprecedented PPh3·HBr-DMSO mediated oxidative bromination and Kornblum oxidation sequence. The newly developed reagent system serves admirably for the synthesis of α-bromoenals from enals. Furthermore, AuCl 3-catalyzed efficient access to 3(2H)-furanones from the above intermediates under extremely mild conditions are described. Copyright
- Mal, Kanchan,Sharma, Abhinandan,Maulik, Prakas R.,Das, Indrajit
-
supporting information
p. 662 - 667
(2014/01/23)
-
- Enantioselective oxidation of secondary alcohols by Candida parapsilosis ATCC 7330
-
Optically pure allylic alcohols and 4-phenylbutan-2-ols were prepared by oxidative kinetic resolution using whole cells of Candida parapsilosis ATCC 7330. Only the 'S' enantiomer is selectively oxidized to the corresponding keto compound (yield, 37-46%) leaving the 'R' alcohol (yield, 37-52% and ee 46 to >99%). The biocatalytic method is carried out under mild conditions at 20°C, pH 6.5 in phosphate buffer.
- Sivakumari, Thakkellapati,Preetha, Radhakrishnan,Chadha, Anju
-
p. 2257 - 2262
(2014/01/06)
-
- Iridium(I)-catalyzed regioselective C-H activation and hydrogen-isotope exchange of non-aromatic unsaturated functionality
-
Isotopic labelling is a key technology of increasing importance for the investigation of new C-H activation and functionalization techniques, as well as in the construction of labelled molecules for use within both organic synthesis and drug discovery. Herein, we report for the first time selective iridium-catalyzed C-H activation and hydrogen-isotope exchange at the β-position of unsaturated organic compounds. The use of our highly active [Ir(cod)(IMes)(PPh3)][PF6] (cod = 1, 5-cyclooctadiene) catalyst, under mild reaction conditions, allows the regioselective β-activation and labelling of a range of α, β-unsaturated compounds with differing steric and electronic properties. This new process delivers high levels of isotope incorporation over short reaction times by using low levels of catalyst loading.
- Kerr, William J.,Mudd, Richard J.,Paterson, Laura C.,Brown, Jack A.
-
supporting information
p. 14604 - 14607
(2015/03/04)
-
- Facile synthesis of Z -alkenes via uphill catalysis
-
Catalytic access to thermodynamically less stable Z-alkenes has recently received considerable attention. These approaches have relied upon kinetic control of the reaction to arrive at the thermodynamically less stable geometrical isomer. Herein, we present an orthogonal approach which proceeds via photochemically catalyzed isomerization of the thermodynamic E-alkene to the less stable Z-isomer which occurs via a photochemical pumping mechanism. We consider two potential mechanisms. Importantly, the reaction conditions are mild, tolerant, and operationally simple and will be easily implemented.
- Singh, Kamaljeet,Staig, Shannon J.,Weaver, Jimmie D.
-
supporting information
p. 5275 - 5278
(2014/05/06)
-
- Aldol reactions mediated by a tetrahedral boronate
-
The base is a key factor in aldol reactions in organic media, determining the selectivity. Here, we describe a tetrahedral phenylboronate salt as a mild non-nucleophilic base that is able to catalyse the aldol reaction and significantly decrease the formation of undesired elimination products. This journal is
- Mueller, Tobias,Djanashvili, Kristina,Arends, Isabel W.C.E.,Peters, Joop A.,Hanefeld, Ulf
-
supporting information
p. 361 - 363
(2013/02/23)
-
- Copper-catalyzed one-pot oxidation-aldol/henry reaction of benzylic amines to α,β-unsaturated methyl ketone/nitro compounds
-
A novel one-pot synthesis of α,β-unsaturated methyl ketone/nitro compounds from benzylic amines through an oxidation-aldol/Henry reaction is reported. The reaction proceeded well by using MCPBA as oxidant and CuCl 2·2H2O as catalyst. A variety of functionalized α,β-unsaturated methyl ketone/nitro compounds were assembled in moderate yields by application of this catalytic one-pot reaction. Georg Thieme Verlag Stuttgart New York.
- Liu, Jia,Zhu, Xiao-Rui,Ren, Jiangmeng,Chen, Wei-Dong,Zeng, Bu-Bing
-
p. 2740 - 2742
(2014/01/06)
-
- Terminal olefins to linear α,β-unsaturated ketones: Pd(II)/hypervalent iodine co-catalyzed wacker oxidation-dehydrogenation
-
Development of a mild (35 C, no Bronsted acids) tandem Wacker oxidation-dehydrogenation of terminal olefins was accomplished using palladium(II) and hypervalent iodine co-catalysis. The reaction affords linear aryl and alkyl α,β-unsaturated ketones directly from readily available terminal olefins in good yields (average 75% per step) with excellent functional group tolerance and chemo- and stereoselectivities. The hypervalent iodine co-catalyst was found to be critical for dehydrogenation but was not effective as a stoichiometric oxidant.
- Bigi, Marinus A.,White, M. Christina
-
p. 7831 - 7834
(2013/07/19)
-
- Enantioselective formal aza-Diels-Alder reactions of enones with cyclic imines catalyzed by primary aminothioureas
-
A highly enantio- and diastereoselective synthesis of indolo- and benzoquinolizidine compounds has been developed through the formal aza-Diels-Alder reaction of enones with cyclic imines. This transformation is catalyzed by a new bifunctional primary aminothiourea that achieves simultaneous activation of both the enone and imine reaction components.
- Lalonde, Mathieu P.,McGowan, Meredeth A.,Rajapaksa, Naomi S.,Jacobsen, Eric N.
-
supporting information
p. 1891 - 1894
(2013/04/10)
-
- Chiral magnesium(II) binaphtholates as cooperative bronsted/lewis acid-base catalysts for the highly enantioselective addition of phosphorus nucleophiles to α,β-unsaturated esters and ketones
-
A little cooperation goes a long way: The cooperative Bronsted/Lewis acid-base supramolecular catalysts formed in situ from simple chiral magnesium(II) binaphtholate aqua complexes promoted the highly enantioselective 1,4-hydrophosphinylation of α,β-unsaturated esters with diaryl phosphine oxides and 1,2-hydrophosphonylation of α,β-unsaturated ketones with dialkyl phosphites (see scheme). Copyright
- Hatano, Manabu,Horibe, Takahiro,Ishihara, Kazuaki
-
supporting information
p. 4549 - 4553
(2013/06/04)
-
- Palladium-catalyzed conjugate addition of arylsulfonyl hydrazides to α,β-unsaturated ketones
-
A palladium-catalyzed desulfitative-denitrogenative conjugate addition of arylsulfonyl hydrazides to α,β-unsaturated ketones is described. The reaction showed very good selectivity and tolerated a wide range of functionalities under an atmosphere of oxygen with or without the aid of a metal co-oxidant. The Royal Society of Chemistry 2013.
- Chen, Wen,Chen, Hui,Xiao, Fuhong,Deng, Guo-Jun
-
supporting information
p. 4295 - 4298
(2013/08/23)
-
- Preparation of monometallic (Pd, Ag) and bimetallic (Pd/Ag, Pd/Ni, Pd/Cu) nanoparticles via reversed micelles and their use in the Heck reaction
-
The metal nanoparticles (NPs) have been prepared using a water-in-oil microemulsion system of water/dioctyl sulfosuccinate sodium salt (aerosol-OT, AOT)/isooctane at 25 °C. Since the NPs produced in this system can endure forcing conditions (100 °C), this system has been used for the synthesis of nano-catalysts in the Heck reactions. FE-SEM, DLS, and UV/vis analyses have been used to characterize the surface morphology, size, and proof of the formation of all the prepared metal NPs, respectively. In addition, the effects of some reaction parameters (here, bases and solvents) were optimized. Differences in the catalytic properties of the synthesized NPs have also been investigated. Consequently, the Pd/Cu (4:1) bimetallic NP showed the highest activity in the C-C coupling reaction of the iodobenzene with the styrene, thus it is employed as the superior catalyst in this study. Therefore, the Pd/Cu (4:1) bimetallic NPs were further investigated using TEM and XRD analyses. This catalyst system is also reusable for six runs with very negligible reduction in the efficiency.
- Heshmatpour, Felora,Abazari, Reza,Balalaie, Saeed
-
experimental part
p. 3001 - 3011
(2012/05/31)
-