- Expedient construction of the [7-5-5] all-carbon tricyclic core of the daphniphyllum alkaloids daphnilongeranin B and daphniyunnine D
-
A synthetic strategy for the construction of the [7-5-5] all-carbon tricyclic core of numerous calyciphylline A-type Daphniphyllum alkaloids has been developed using a key intramolecular Pauson-Khand reaction. A subsequent base-mediated double-bond migration and a regio-and stereoselective radical late stage allylic oxygenation provide access to the substitution patterns of daphnilongeranin B and daphniyunnine D.
- Darses, Benjamin,Michaelides, Iacovos N.,Sladojevich, Filippo,Ward, John W.,Rzepa, Paula R.,Dixon, Darren J.
-
-
Read Online
- Antimalarial activity of compounds interfering with Plasmodium falciparum phospholipid metabolism: Comparison between mono- and bisquaternary ammonium salts
-
On the basis of a previous structure - activity relationship study, we identified some essential parameters, e.g. electronegativity and lipophilicity, required for polar head analogues to inhibit Plasmodium falciparum phospholipid metabolism, leading to parasite death. To improve the in vitro antimalarial activity, 36 cationic choline analogues consisting of mono-, bis-, and triquaternary ammonium salts with distinct substituents of increasing lipophilicity were synthesized. For monoquaternary ammonium salts, an increase in the lipophilicity around nitrogen was beneficial for antimalarial activity: IC50 decreased by I order of magnitude from trimethyl to tripropyl substituents. Irrespective of the polar head substitution (methyl, ethyl, hydroxyethyl, pyrrolidinium), increasing the alkyl chain length from 6 to 12 methylene groups always led to increased activity. The highest activity was obtained for the N,N,N-tripropyl-N-dodecyl substitution of nitrogen (IC50 33 nM). Beyond 12 methylene groups, the antimalarial activities of the compounds decreased slightly. The structural requirements for bisquaternary ammonium salts in antimalarial activity were very similar to those of monoquaternary ammonium salts, i.e. polar head steric hindrance and lipophilicity around nitrogen (methyl, hydroxyethyl, ethyl, pyrrolidinium, etc.). In contrast, with bisquaternary ammonium salts, increasing the lipophilicity of the alkyl chain between the two nitrogen atoms (from 5 to 21 methylene groups) constantly and dramatically increased the activity. Most of these duplicated molecules had activity around 1 nM, and the most lipophilic compound synthesized exhibited an IC50 as low as 3 pM (21 methylene groups). Globally, this oriented synthesis produced 28 compounds out of 36 with an IC50 lower than 1 μM, and 9 of them had an IC50 in the nanomolar range, with I compound in the picomolar range. This indicates that developing a pharmacological model for antimalarial compounds through choline analognes is a promising strategy.
- Calas, Michèle,Ancelin, Marie L.,Cordina, Gérard,Portefaix, Philippe,Piquet, Gilles,Vidal-Sailhan, Valérie,Vial, Henri
-
-
Read Online
- A bifunctional amino acid to study protein-protein interactions
-
Protein-protein interactions (PPIs) play crucial roles in regulating essentially all cellular processes. Photo-cross-linking represents a powerful method to study PPIs. To fulfil the requirements for the exploration of different PPIs, there is a continuous demand on the development of novel photo-reactive amino acids with diverse structural properties and functionalities. Reported herein is the development of a bifunctional amino acid termed dzANA, which contains a diazirine, for photo-cross-linking, and a terminal alkyne group, for bioorthogonal tagging. Using known PPIs between histone posttranslational modifications (PTMs) and their binding partners as models, we demonstrate that the dzANA-harbouring peptide-based photoaffinity probes could efficiently and selectively capture the weak and transient PPIs mediated by histone modifications. Our study indicates the potential of dzANA to identify and characterize unknown PPIs. This journal is
- Li, Xiang David,Li, Xin,Yang, Tangpo
-
-
Read Online
- Synthesis of 5-tethered carborane-containing pyrimidine nucleosides as potential agents for DNA incorporation
-
Several 5-substituted-2'-deoxyuridines have been prepared in which the carborane moiety is attached at the terminus of a flexible hydrocarbon chain containing an ester linkage. These boron moieties as the B-10 enriched compounds have potentially for use in the treatment of cancer by means of boron neutron capture therapy. A convenient synthetic route, in high yield, has been developed for the preparation of these 5-tethered carborane- containing pyrimidine nucleosides.
- Rong,Soloway
-
-
Read Online
- Diversity oriented synthesis of pyran based polyfunctional stereogenic macrocyles and their conformational studies
-
A new approach to synthesize a homologous series of 14-, 15-, and 16-membered drug-like, macrocyclic glycoconjugates involving TBAHS promoted azide-propenone intramolecular cycloaddition in designed C-glycopyranosyl butenones from a simple sugar D-glucose and D-mannose is reported.
- Ajay, Arya,Sharma, Shrikant,Gupt, Munna Prasad,Bajpai, Vikas,Hamidullah,Kumar, Brijesh,Kaushik, Mahabir Prasad,Konwar, Rituraj,Ampapathi, Ravi Sankar,Tripathi, Rama Pati
-
-
Read Online
- Bifunctional Fluoroalcohol Catalysts Enabled Sustainable Synthesis of Poly(amino acid)s?
-
A series of novel bifunctional single-molecule hydrogen-bonding organocatalysts based on fluorinated tertiary alcohol were synthesized to mediate the metal-free polymerization of α-amino acid N-carboxyanhydride (NCA) monomer. Through the screening of catalysts, the polymerization catalyzed by the preferred bifunctional fluoroalcohol catalyst proceeded in a fast and controlled manner, affording high molecular weight polypeptide up to 35.2 × 104 Da with relatively narrow molecular weight distribution (? 1.20). A phenomenon of self-accelerating effect of polymerization induced by α-helical structure of polypeptides was observed, and a possible polymerization pathway has been discussed.
- He, Wenjing,Tao, Youhua
-
supporting information
p. 2119 - 2124
(2021/06/16)
-
- Design and Synthesis of Oleanolic Acid Trimers to Enhance Inhibition of Influenza Virus Entry
-
Influenza is a major threat to millions of people worldwide. Entry inhibitors are of particular interest for the development of novel therapeutic strategies for influenza. We have previously discovered oleanolic acid (OA) to be a mild influenza hemagglutinin (HA) inhibitor. In this work, inspired by the 3D structure of HA as a homotrimeric receptor, we designed and synthesized 15 OA trimers with different linkers and central region via the copper-catalyzed azide-alkyne cycloaddition reaction. All of the OA trimers were evaluated for their antiviral activities in vitro, and 12c, 12e, 13c, and 13d were observed to exhibit robust potency (IC50 in the submicromolar range) against influenza A/WSN/33 (H1N1) virus that was stronger than that observed with oseltamivir. In addition, these compounds also displayed strong biological activity against A/Hong Kong/4801/2014 and B/Sichuan/531/2018 (BV). The results of hemagglutination inhibition assays and surface plasmon resonance binding assays suggest that these OA trimers may interrupt the interaction between the HA protein of influenza virus and the host cell sialic acid receptor, thus blocking viral entry. These findings highlight the utility of multivalent OA conjugates to enhance the ligand-target interactions in anti-influenza virus drug design and are also helpful for studying antiviral drugs derived from natural products.
- Huang, Boxuan,Li, Weijia,Mu, Yu,Shao, Liang,Su, Yangqing,Sun, Mengsi,Xu, Huan,Yang, Fan,Yu, Fei,Zhang, Jihong,Zhang, Yuan
-
p. 1759 - 1765
(2021/11/18)
-
- 3,6-DISUBSTITUTED-2-PYRIDINALDOXIME SCAFFOLDS
-
The present invention relates to a compound of formula (I), or one of its pharmaceutically acceptable salts: wherein R1, R2 and -X-Y- have specific definitions. It also relates to the use of such a compound as reactivator of acetylcholinesterase for treating organophosphorous nerve agents poisoning; and to a process for preparing it.
- -
-
Paragraph 0095; 0175-0177
(2020/08/27)
-
- Catalytic Asymmetric Synthesis of α-Arylpyrrolidines and Benzo-fused Nitrogen Heterocycles
-
Herein, we report a practical two-step synthetic route to α-arylpyrrolidines through Suzuki–Miyaura cross-coupling and enantioselective copper-catalyzed intramolecular hydroamination reactions. The excellent stereoselectivity and broad scope for the transformation of substrates with pharmaceutically relevant heteroarenes render this method a practical and versatile approach for pyrrolidine synthesis. Additionally, this intramolecular hydroamination strategy facilitates the asymmetric synthesis of tetrahydroisoquinolines and medium-ring dibenzo-fused nitrogen heterocycles.
- Dai, Xi-Jie,Engl, Oliver D.,León, Thierry,Buchwald, Stephen L.
-
supporting information
p. 3407 - 3411
(2019/02/24)
-
- [18F]FPyZIDE: A versatile prosthetic reagent for the fluorine-18 radiolabeling of biologics via copper-catalyzed or strain-promoted alkyne-azide cycloadditions
-
Methods for the radiolabeling of biologics with fluorine-18 have been of interest for several decades. A common approach consists in the preparation of a prosthetic reagent, a small molecule bearing a fluorine-18 that is conjugated with the macromolecule to an appropriate function. Click chemistry, and more particularly cycloadditions, is an interesting approach to radiolabel molecules thanks to mild reaction conditions, high yields, low by-products formation, and strong orthogonality. Moreover, the chemical functions involved in the cycloaddition reaction are stable in the drastic radiofluorination conditions, thus allowing a simple radiosynthetic route to prepare the prosthetic reagent. We report herein the radiosynthesis of 18F-FPyZIDE, a pyridine-based azide-bearing prosthetic reagent. We exemplified its conjugation via copper-catalyzed cycloaddition (CuAAC) and strain-promoted cycloaddition (SPAAC) with several terminal alkyne or strained alkyne model compounds.
- Roche, Mélanie,Specklin, Simon,Richard, Mylène,Hinnen, Fran?oise,Génermont, Kevin,Kuhnast, Bertrand
-
-
- C19 is fluorinated Largazole analogs, its preparation and use (by machine translation)
-
The invention belongs to the field of pharmacy, of formula (I) shown in the marine natural product of the cyclic ester peptide that marine natural product Largazole fluorinated analogs, its preparation method and for pharmacy via, in vitro HDACs inhibiting activity test, the results display, said compound of the invention has strong, selective inhibition of the function of HDACs, further, containing the compounds of the invention of the medicament or its composition can be prepared anti-tumor therapeutic agent. (by machine translation)
- -
-
Paragraph 0078; 0079; 0080
(2019/01/23)
-
- HETEROCYCLIC COMPOUNDS AS RSV INHIBITORS
-
The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit Respiratory Syncytial Virus (RSV). The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from RSV infection. The invention also relates to methods of treating an RSV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
- -
-
Paragraph 0453-0454
(2019/01/15)
-
- External Oxidant-Free Oxidative Tandem Cyclization: NaI-Catalyzed Thiolation for the Synthesis of 3-Thiosubstituted Pyrroles
-
A simple method for the synthesis of 3-thiosubstituted pyrroles from homopropargylic amines and thiosulfonates via a tandem sulfenylation/cyclization has been developed. The thiosulfonates are used both as substrates and oxidants in this transformation. This procedure exhibits good functional group tolerance and a series of 3-thiosubstituted pyrrole derivatives was obtained in moderate to good yields. (Figure presented.).
- Yuan, Bingxiang,Jiang, Yong,Qi, Zhenjie,Guan, Xin,Wang, Ting,Yan, Rulong
-
supporting information
p. 5112 - 5117
(2019/11/11)
-
- 1 - Azaspiro [4.4] nonane - 6 - one of the preparation method (by machine translation)
-
The present invention relates to 1 - azaspiro [4.4] nonane - 6 - one of the preparation method, in order to [...] propanol as raw materials, through the hydroxyl protection, 1, 2 addition, substitution reaction, through semipinacol method of rearrangement of framed racemic aza [4.4] spiro compounds, through the chiral separation separation product is obtained. Compared with the prior art, whole process of this invention is simple and efficient, can be a large number of preparation two configurations compound, for the preparation of various types of SPD chiral ligand and chiral catalyst. (by machine translation)
- -
-
Paragraph 0035; 0036; 0055; 0063; 0071
(2018/04/26)
-
- The Divergent Cascade Reactions of Arylalkynols with Homopropargylic Amines or Electron-Deficient Olefins: Access to the Spiro-Isobenzofuran- b-pyrroloquinolines or Bridged-Isobenzofuran Polycycles
-
Two divergent cascade reactions of arylalkynols with homopropargylic amines or electron-deficient olefins were developed to synthesize the spiro-isobenzofuran-b-pyrroloquinolines or bridged-isobenzofuran heterocycles in good yields, respectively. One reaction actually involved intramolecular 5-endo-dig hydroamination cyclization-protonation of homopropargylic amines to give cycloiminium ions and intramolecular 5-exo-dig hydroalkoxylation cyclization of arylalkynols to generate isobenzofuran with exocyclic double bond, followed by the nontypical Povarov-type reaction in the presence of PtCl2/FeCl3 cocatalysts. The other underwent intramolecular hydroalkoxylation cycloisomerization of alkynols with the subsequent normal [4 + 2] cycoaddition with dienophiles. Herein, the arylalkynols acted as both "masked" electron-rich olefins and "masked" electron-rich dienes.
- Wang, Lun,Liu, Lingyan,Chang, Weixing,Li, Jing
-
supporting information
p. 7799 - 7813
(2018/06/18)
-
- Tert-Butyl Nitrite Promoted Oxidative Intermolecular Sulfonamination of Alkynes to Synthesize Substituted Sulfonyl Pyrroles from the Alkynylamines and Sulfinic Acids
-
tert-Butyl nitrite promoted oxidative intermolecular sulfonamination of alkynes to synthesize substituted sulfonyl pyrroles from the alkynylamines and sulfinic acids via tandem addition/cyclization was developed. This reaction is performed well by employing tert-butyl nitrite as the oxidant, and various substituted sulfonyl pyrroles are formed in moderate to good yields with no requirement of metal catalysis.
- Qi, Zhenjie,Jiang, Yong,Wang, Yanyan,Yan, Rulong
-
supporting information
p. 8636 - 8644
(2018/06/18)
-
- Cu-Catalyzed Tandem Aerobic Oxidative Cyclization for the Synthesis of 3,3′-Bipyrroles from the Homopropargylic Amines
-
A Cu-catalyzed method for the synthesis of 3,3′-bipyrroles from homopropargylic amines through tandem aerobic oxidative cyclization involving the formation of C-C bond has been developed. The features of this reaction are a small number of Cu catalysis and simple starting substrates. Moreover, this procedure exhibits good functional group tolerance and a series of 3,3′-bipyrroles derivatives are obtained in moderate to good yields.
- Qi, Zhenjie,Jiang, Yong,Yuan, Bingxiang,Niu, Yanning,Yan, Rulong
-
supporting information
p. 5048 - 5052
(2018/08/24)
-
- Highly Efficient and Stereoselective Thioallylation of Alkynes: Possible Gold Redox Catalysis with No Need for a Strong Oxidant
-
Stereoselective thioallylation of alkynes under possible gold redox catalysis was accomplished with high efficiency (as low as 0.1 % catalyst loading, up to 99 % yield) and broad substrate scope (various alkynes, inter- and intramolecular fashion). The gold(I) catalyst acts as both a π-acid for alkyne activation and a redox catalyst for AuI/III coupling, whereas the sulfonium cation generated in situ functions as a mild oxidant. This novel methodology provides an exciting system for gold redox catalysis without the need for a strong oxidant.
- Wang, Jin,Zhang, Shuyao,Xu, Chang,Wojtas, Lukasz,Akhmedov, Novruz G.,Chen, Hao,Shi, Xiaodong
-
supporting information
p. 6915 - 6920
(2018/05/14)
-
- Using Ring Strain to Control 4π-Electrocyclization Reactions: Torquoselectivity in Ring Closing of Medium-Ring Dienes and Ring Opening of Bicyclic Cyclobutenes
-
Syntheses of strained cyclic dienes were accomplished via palladium(II)-catalyzed oxidative cyclizations of terminal bis(vinylboronate esters). The reactions generate strained (E,E)-1,3-dienes that undergo spontaneous 4π-electrocyclizations to form bicyclic cyclobutenes. Formation of the cyclobutenes is driven by the strain in the medium-ring (E,E)-1,3-diene intermediate. Thermal ring openings of the cyclobutenes give (Z,Z)-1,3-diene products, again for thermodynamic reasons. DFT calculations verified the thermodynamic versus kinetic control of the reactions, and kinetic studies are in excellent agreement with the calculated energy changes. An extension of the tandem coupling/4π-electrocyclization pathway was demonstrated by a palladium(II)-catalyzed oxidative homocoupling/8π-electrocyclization cascade.
- Boon, Byron A.,Green, Aaron G.,Liu, Peng,Houk,Merlic, Craig A.
-
p. 4613 - 4624
(2017/05/12)
-
- Regioselective Ni-Catalyzed Carboxylation of Allylic and Propargylic Alcohols with Carbon Dioxide
-
An efficient Ni-catalyzed reductive carboxylation of allylic alcohols with CO2 has been successfully developed, providing linear β,γ-unsaturated carboxylic acids as the sole regioisomer with generally high E/Z stereoselectivity. In addition, the carboxylic acids can be generated from propargylic alcohols via hydrogenation to give allylic alcohol intermediates, followed by carboxylation. A preliminary mechanistic investigation suggests that the hydrogenation step is made possible by a Ni hydride intermediate produced by a hydrogen atom transfer from water.
- Chen, Yue-Gang,Shuai, Bin,Ma, Cong,Zhang, Xiu-Jie,Fang, Ping,Mei, Tian-Sheng
-
supporting information
p. 2969 - 2972
(2017/06/07)
-
- Silver-Catalyzed Three-Component 1,1-Aminoacylation of Homopropargylamines: α-Additions for Both Terminal Alkynes and Isocyanides
-
The reaction of secondary homopropargylamines, isocyanides, and water in the presence of a catalytic amount of silver acetate and subsequent purification by chromatography on silica gel afforded substituted proline amides in good to excellent yields. Primary homopropargylamines underwent a cyclizative Ugi–Joullié three-component reaction with isocyanides and carboxylic acids to afford functionalized N-acyl proline amides. High diastereoselectivity was observed in the synthesis of 4-alkoxy and 4,5-disubstituted proline derivatives. This work represents the first examples of a three-component cyclizative 1,1-aminoacylation of terminal alkynes.
- Tong, Shuo,Piemontesi, Cyril,Wang, Qian,Wang, Mei-Xiang,Zhu, Jieping
-
supporting information
p. 7958 - 7962
(2017/06/27)
-
- Total synthesis of (±)-20: S -hydroxy-1,2-dehydro-pseudoaspidospermidine via a C-H activation/transannular cyclization strategy
-
A total synthesis to the pseudoaspidospermidine family via a C-H activation/transannular cyclization strategy has been accomplished. The applicability of this approach is showcased in the concise synthesis (ten steps) of (±)-20S-hydroxy-1,2-dehydro-pseudoaspidospermidine (4) starting from literature known compound 11. Via a joint synthetic sequence we were also able to address the related iboga alkaloid (±)-isovelbanamine (7) in nine steps. Key features of this synthesis are a transannular cyclization to generate the pseudoaspidospermidine skeleton (C-H activation) and a Witkop photocyclization reaction providing a 9-membered lactam. It is also worth mentioning that the joint synthetic sequence can be carried out on a multigram scale.
- Leitner, Christian,Gaich, Tanja
-
supporting information
p. 7451 - 7453
(2017/07/12)
-
- Gold-Catalyzed Cycloisomerization of Alkyne-Containing Amino Acids: Controlled Tuning of C–N vs. C–O Reactivity
-
Versatile alkyne-containing amino acids were used as ambident precursors in the divergent synthesis of alkylidenelactones and 1-pyrrolines. Two gold-catalyzed protocols were applied for selective intramolecular O- and N-cycloisomerization reactions.
- Medran, Noelia S.,Villalba, Matías,Mata, Ernesto G.,Testero, Sebastián A.
-
p. 3757 - 3764
(2016/08/16)
-
- GLS1 INHIBITORS FOR TREATING DISEASE
-
Disclosed herein are compounds and compositions useful in the treatment of GLS1 mediated diseases, such as cancer, having the structure of Formula I. Methods of inhibition GLS1 activity in a human or animal subject are also provided.
- -
-
Paragraph 0229
(2016/01/25)
-
- Palladium(II)-Catalyzed Regioselective syn-Hydroarylation of Disubstituted Alkynes Using a Removable Directing Group
-
A palladium(II)-catalyzed regioselective syn-hydroarylation reaction of homopropargyl amines has been developed, wherein selectivity is controlled by a cleavable bidentate directing group. Under the optimized reaction conditions, both dialkyl and alkylaryl alkyne substrates were found to undergo hydroarylation with high selectivity. The products of this reaction contain a 4,4-disubstituted homoallylic amine motif that is commonly seen in drug molecules and other bioactive compounds.
- Liu, Zhen,Derosa, Joseph,Engle, Keary M.
-
supporting information
p. 13076 - 13081
(2016/10/13)
-
- TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE
-
Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.
- -
-
Paragraph 0313; 0314
(2016/12/22)
-
- Design and Synthesis of 2-Alkylpyrimidine-4,6-diol and 6-Alkylpyridine-2,4-diol as Potent GPR84 Agonists
-
A series of alkylpyrimidine-4,6-diol derivatives were designed and synthesized as novel GRP84 agonists based on a high-throughput screening (HTS) hit 1. 6-Nonylpyridine-2,4-diol was identified as the most potent agonist of GPR84 reported so far, with an EC50 of 0.189 nM. These novel GPR84 agonists will provide valuable tools for the study of the physiological functions of GPR84.
- Liu, Yang,Zhang, Qing,Chen, Lin-Hai,Yang, Hui,Lu, Wei,Xie, Xin,Nan, Fa-Jun
-
supporting information
p. 579 - 583
(2016/07/06)
-
- Regioselective Amine–Borane Cyclization: Towards the Synthesis of 1,2-BN-3-Cyclohexene by Copper-Assisted Triazole/Gold Catalysis
-
The combination of triazole/gold (TA-Au) and Cu(OTf)2is identified as the optimal catalytic system for promoting intramolecular hydroboration for the synthesis of a six-membered cyclic amine–borane. Excellent yields (up to 95 %) and regioselectivities (5-exo vs. 6-endo) were achieved through catalyst control and sequential dilution. Good functional-group tolerance was attained, thus allowing the preparation of highly functionalized cyclic amine–borane substrates, which could not be achieved using other methods. Deuterium-labeling studies support the involvement of a hydride addition to a gold-activated alkyne with subsequent C?B bond formation.
- Motika, Stephen E.,Wang, Qiaoyi,Akhmedov, Novruz G.,Wojtas, Lukasz,Shi, Xiaodong
-
supporting information
p. 11582 - 11586
(2016/10/24)
-
- 2′-Deoxy-2′,2′-difluorothymidine analogues for radiolabeling with fluorine-18 and other biomedical applications
-
Novel 2′-deoxy-2′,2′-difluorothymidine analogues with potential applications as antiviral, cytotoxic and cancer imaging agents have been synthesized. Introduction of the hydroxymethyl functionality at the 5-position of 2′-deoxy-2′,2′-difluoruridine provided a key intermediate with a suitable synthetic handle for the generation of these nucleoside derivatives.
- Doepner, Andreas M.,Aboagye, Eric O.,Barrett, Anthony G.M.
-
supporting information
p. 3293 - 3297
(2015/03/04)
-
- Cyclization of gold acetylides: Synthesis of vinyl sulfonates via gold vinylidene complexes
-
Differently substituted terminal alkynes that bear sulfonate leaving groups at an appropriate distance were converted in the presence of a propynyl gold(I) precatalyst. After initial formation of a gold acetylide, a cyclization takes place at the β-carbon atom of this species. Mechanistic studies support a mechanism that is related to that of dual gold-catalyzed reactions, but for the new substrates, only one gold atom is needed for substrate activation. After formation of a gold vinylidene complex, which forms a tight contact ion pair with the sulfonate leaving group, recombination of the two parts delivers vinyl sulfonates, which are valuable targets that can serve as precursors for cross-coupling reactions, for example. Gold vinylidene intermediates are generated by the cyclization of gold acetylides that carry a sulfonate leaving group. This result demonstrates for the first time that the formation of these species is not restricted to a dual activation mode. The cyclization products obtained herein contain a vinyl sulfonate moiety, which makes them useful building blocks for cross-coupling reactions.
- Bucher, Janina,Wurm, Thomas,Nalivela, Kumara Swamy,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
-
supporting information
p. 3854 - 3858
(2014/05/06)
-
- Directing group enhanced carbonylative ring expansions of amino-substituted cyclopropanes: Rhodium-catalyzed multicomponent synthesis of N-heterobicyclic enones
-
Aminocyclopropanes equipped with suitable N-directing groups undergo efficient and regioselective Rh-catalyzed carbonylative C-C bond activation. Trapping of the resultant metallacycles with tethered alkynes provides an atom-economic entry to diverse N-heterobicyclic enones. These studies provide a blueprint for myriad N-heterocyclic methodologies.
- Shaw, Megan H.,Melikhova, Ekaterina Y.,Kloer, Daniel P.,Whittingham, William G.,Bower, John F.
-
supporting information
p. 4992 - 4995
(2013/05/22)
-
- Agri-Horticultural Pest Control Compositions Comprising 4-(3-Butynyl)Aminopyrimidine Derivatives
-
Agri-horticultural pest control compositions having outstanding control effect on pests, in particular, agri-horticultural pests, which comprise as active ingredients one or more 4-(3-butynyl)aminopyrimidine derivatives represented by the general formula [I], namely, where R1 is typically selected from among: a) phenyl c) —SiR5R6R7 (R5, R6, and R7 which may be the same or different represent a linear or branched alkyl having 1-6 carbon atoms, a linear or branched haloalkyl having 1-3 carbon atoms which is substituted by one halogen atom, a linear or branched cyanoalkyl having 1-3 carbon atoms which is substituted by one cyano group, and phenyl); d) hydropgen atom; R2 typically represents a hydrogen atom; R3 typically represents a hydrogen atom; R4 represents a hydrogen atom and one or more agri-horticultural pest control compounds selected from among agri-horticultural antimicrobial compounds, say, multi-site contact active compouns, nucleic acids synthesis inhibitory active compounds, mitosis and cell divesion inhibitory active compounds, and/or agri-horticultural insecticidal, miticidal or nematicidal compounds, say, acetylcholinesterase inhibitors, GABA-gated chloride antagonists, and sodium channel modulators. Since the 4-(3-butynyl)aminopyrimidine derivatives and the existing antimicrobial active compounds and/or insecticidal active compounds are used in admixture, the 4-(3-butynyl)aminopyrimidine derivatives which are useful as pest control agents, particularly as agri-horticultural pest control agents, need be used in smaller amounts and yet their antimicrobial or insecticidal activity can be improved.
- -
-
Paragraph 0151
(2013/11/19)
-
- Fused ring aziridines as a facile entry into triazole fused tricyclic and bicyclic heterocycles
-
The intramolecular dipolar cycloaddition of an azide with an alkyne has provided a useful entry into triazole fused tricyclic heterocycles containing both the triazole ring and the oxazolidin-2-one ring system. The requisite azido-alkynes have been prepared via a two-step sequence from fused ring aziridines. A series of 6-12 membered rings containing both the oxazolidinone and triazole rings have been prepared. These ring systems have been designed as conformationally restrained analogs of RNA-binding oxazolidinones. The Royal Society of Chemistry 2012.
- Fang, Fang,Vogel, Megan,Hines, Jennifer V.,Bergmeier, Stephen C.
-
scheme or table
p. 3080 - 3091
(2012/05/07)
-
- Asymmetric total synthesis of (+)-virosine A via sequential nucleophilic cyclizations onto an activated formamide
-
The first synthesis of tetracyclic alkaloid virosine A is reported. The natural alkaloid was prepared in only 13 steps, in an enantioenriched form. The azabicyclo[2.2.2]octane core was efficiently assembled using a key Vilsmeier-Haack and Mannich cyclizations sequence performed in one pot.
- Belanger, Guillaume,Dupuis, Marianne,Larouche-Gauthier, Robin
-
experimental part
p. 3215 - 3221
(2012/05/19)
-
- Reductive Heck coupling: An efficient approach toward the iboga alkaloids. Synthesis of ibogamine, epiibogamine and iboga analogs
-
A mild and efficient synthetic route to the iboga scaffold by employing reductive-Heck type annulation is described. The utility of this process is demonstrated by the direct access to the ibogamine, epiibogamine and iboga-analogs. The cyclization precursors were readily obtained from 2-iodoaniline by heteroannulation reaction with suitable alkynes followed by iodination.
- Jana, Goutam Kumar,Sinha, Surajit
-
supporting information; experimental part
p. 1671 - 1674
(2012/04/11)
-
- 4-(3-BUTYNYL)AMINOPYRIMIDINE DERIVATIVES AS PEST CONTROL AGENTS FOR AGRICULTURAL AND HORTICULTURAL USE
-
Novel 4-(3-butynyl)aminopyrimidine derivatives represented by general formula [I] are useful as pest control agents. In general formula [I], R1 is a mono- or bi-cyclic ring which may contain 0 to 3 heteroatoms, for example, phenyl or oxazolyl; R2 is a hydrogen atom, -R, -OR, -C(O)OR, -C(O)NHR, -CONR2 (wherein R is straight-chain or branched C1-8 alkyl, or the like), hydroxyalkyl, or the like; R3 is a hydrogen atom, a halogen atom, acyloxy represented by (straight-chain or branched C1-8 aliphatic hydrocarbon group) -CO-O-, or the like; and R4 is a hydrogen atom, a halogen atom, C1-6 alkyl, or the like, or alternatively, R4 and R3 together with the carbon atoms on the pyrimidine ring may form a thiophene ring, a pyrrole ring, an imidazole ring, a benzene ring, a pyrimidine ring, a furan ring, a pyrazine ring, or a pyrrolidine ring.
- -
-
Page/Page column 19
(2012/06/01)
-
- Improved synthesis of C8-C20 segment of pectenotoxin-2
-
The C8-C20 segment of pectenotoxin-2 was efficiently synthesized in 16% overall yield in 22 steps from l-malic acid via an improved route.
- Fujiwara, Kenshu,Suzuki, Yuki,Koseki, Nao,Murata, Shun-Ichi,Murai, Akio,Kawai, Hidetoshi,Suzuki, Takanori
-
scheme or table
p. 5589 - 5592
(2011/11/07)
-
- Selection of the biological activity of DNJ neoglycoconjugates through click length variation of the side chain
-
A series of neoglycoconjugates derived from deoxynojirimycin has been prepared by click connection with functionalised adamantanes. They have been assayed as glycosidase inhibitors, as inhibitors of the glycoenzymes relevant to the treatment of Gaucher disease, as well as correctors of the defective ion-transport protein involved in cystic fibrosis. We have demonstrated that it is possible to selectively either strongly inhibit ER-α-glucosidases and ceramide glucosyltransferase or restore the activity of CFTR in CF-KM4 cells by varying the length of the alkyl chain linking DNJ and adamantane.
- Ardes-Guisot, Nicolas,Alonzi, Dominic S.,Reinkensmeier, Gabriele,Butters, Terry D.,Norez, Caroline,Becq, Frederic,Shimada, Yousuke,Nakagawa, Shinpei,Kato, Atsushi,Bleriot, Yves,Sollogoub, Matthieu,Vauzeilles, Boris
-
supporting information; experimental part
p. 5373 - 5388
(2011/08/22)
-
- Tandem electrocyclic ring opening/radical cyclization: Application to the total synthesis of cribrostatin 6
-
A concise total synthesis of cribrostatin 6 (1), an antimicrobial and antineoplastic agent, was accomplished using a tandem electrocyclic ring opening/radical cyclization sequence. Specifically, intermediate 4 underwent a 4π-electrocyclic ring opening, radical cyclization, and homolytic aromatic substitution sequence followed by an oxidation to afford the natural product 1 in one pot. Owing to the rapid buildup of complexity in the key step, 1 could be synthesized from commercially available starting materials in only four linear steps. Application of this chemistry to the concise syntheses of analogs of cribrostatin 6 (1) is also reported.
- Knueppel, Daniel,Martin, Stephen F.
-
experimental part
p. 9765 - 9770
(2012/02/05)
-
- Evaluation of α-pyrones and pyrimidones as photoaffinity probes for affinity-based protein profiling
-
α-Pyrones and pyrimidones are common structural motifs in natural products and bioactive compounds. They also display photochemistry that generates high-energy intermediates that may be capable of protein reactivity. A library of pyrones and pyrimidones was synthesized, and their potential to act as photoaffinity probes for nondirected affinity-based protein profiling in several crude cell lysates was evaluated. Further "proof-of-principle" experiments demonstrate that a pyrimidone tag on an appropriate scaffold is equally capable of proteome labeling as a benzophenone.
- Battenberg, Oliver A.,Nodwell, Matthew B.,Sieber, Stephan A.
-
experimental part
p. 6075 - 6087
(2011/10/09)
-
- Facile synthesis of dihaloheterocycles via electrophilic iodocyclization
-
An efficient and facile electrophilic iodocyclization for the synthesis of various O-, N-, and S-containing dihaloheterocycles has been developed. A wide range of the substituted propargyl alcohols having -OH, -NTs, and -SAc functional groups reacted with molecular iodine or bromoiodine at ambient temperature to produce the corresponding dihalogenated O-, N-, and S-containing five- and six-membered heterocycles in good to high yields; Under optimized solvent conditions, the reactions of various substituted but-2-yn-1-ones bearing -OH, -NTs, and -SAc functional groups at C4-position, with iodine or bromoiodine at ambient temperature afforded the corresponding 3,4-diiodo- and 3-bromo-4-iodo-substituted furans, pyrroles, and thiophenes in good to high yields. Further transformation of the resulting iodine- or bromine-containing products to polyaromatics potentially of useful as organo-material intermediates has been investigated.
- Yang, Fan,Jin, Tienan,Bao, Ming,Yamamoto, Yoshinori
-
supporting information; scheme or table
p. 10147 - 10155
(2012/01/03)
-
- Clickable peptide nucleic acids (cPNA) with tunable affinity
-
Peptide nucleic acids (PNAs) are functional analogues of natural oligonucleotides. Herein, we report the synthesis of PNAs bearing a triazole in lieu of the amide bond assembled using a "click" cycloaddition, their hybridization properties as well as the DNA-templated coupling of the azide and alkyne PNA fragments. The Royal Society of Chemistry 2010.
- Chouikhi, Dalila,Barluenga, Sofia,Winssinger, Nicolas
-
supporting information; experimental part
p. 5476 - 5478
(2010/10/19)
-
- A concise route to iboga-analogues via the formation of suitably substituted-2-indoles
-
A concise route to iboga-analogues has been developed. Important steps include a Pd-catalyzed Sonogashira coupling of Boc-2-idodaniline with terminal alkynes and the formation of 2-substituted indoles in the presence of tetrabutylammonium fluoride to give the key intermediate, dehydroisoquinuclidine-containing indole. The final step cyclization between indole-3-position and dehydroisoquinuclidine ring was achieved using Pd(II)-Ag(I) mixed metal-mediated cyclization method. Both exo- and endo-substitution with -CO2Me at C19 have been reported.
- Jana, Goutam Kumar,Sinha, Surajit
-
supporting information; experimental part
p. 1994 - 1996
(2010/06/21)
-
- Evaluation and optimization of antifibrotic activity of cinnamoyl anthranilates
-
Tranilast is an anti-inflammatory drug in use for asthma and atopic dermatitis. In studies over the last decade it has been revealed that tranilast can reduce fibrosis occurring in the kidney during diabetes, thereby delaying and/or preventing kidney dysfunction. We report a structure-activity study aimed at optimizing the antifibrotic activity of tranilast. A series of cinnamoyl anthranilates were prepared and assessed for their ability to prevent TGF-β-stimulated production of collagen in cultured renal mesangial cells. We reveal derivatives with improved potency and reduced cellular toxicity relative to tranilast. 3-Methoxy-4-propargyloxycinnamoyl anthranilate reduces albuminuria in a rat model of progressive diabetes, and thus has potential as an innovative treatment for diabetic nephropathy.
- Zammit, Steven C.,Cox, Alison J.,Gow, Renae M.,Zhang, Yuan,Gilbert, Richard E.,Krum, Henry,Kelly, Darren J.,Williams, Spencer J.
-
supporting information; experimental part
p. 7003 - 7006
(2010/07/08)
-
- Pd-catalyzed borylative cyclization of allenynes and enallenes
-
Pd-catalyzed cyclization of 1,5- and 1,6-allenynes and 1,5-enallenes with bis(pinacolato)diboron affords synthetically useful allylboronates and alkylboronates under smooth conditions in a formal hydroborylative carbocyclization reaction. One C-C and one
- Pardo-Rodriguez, Virtudes,Marco-Martinez, Juan,Bunuel, Elena,Cardenas, Diego J.
-
supporting information; experimental part
p. 4548 - 4551
(2009/12/07)
-
- Synthesis of pyridines and pyrazines using an intramolecular hydroamination-based reaction sequence
-
A management issue! Various pyridines and pyrazines can be efficiently accessed from simple acyclic precursors using an intramolecular hydroamination/isomerization/aromatization sequence (see scheme). ρ-Toluenesulfonic acid (2 mol%) is used to catalyze this novel alkyne annulation, in which the oxime group allows for a subsequent redoxneutral aromatization step to occur.
- Rizk, Toni,Bilodeau, Eric J.-F.,Beauchemin, Andre M.
-
supporting information; experimental part
p. 8325 - 8327
(2010/01/16)
-
- BICYCLIC HETEROCYCLE DERIVATIVES AND USE THEREOF AS GPR119 MODULATORS
-
The present invention relates to Bicyclic Heterocycle Derivatives of formula (I), compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of GPR1 19 in a patient.
- -
-
Page/Page column 216
(2009/12/27)
-
- An unusual access to medium sized cycloalkynes by a new goId(I)-catalysed cycloisomerisation of diynes
-
A study was conducted to demonstrate efficient cycloisomerization of a series of 1,9- and 1,10-diynes into medium sized cycloalkynes by a gold-catalyzed alkyne-alkyne coupling. The reaction was performed using 4 mol% of gold complex in CD2Cl2 at room temperature and was monitored by using 1H NMR spectroscopy. The reaction of analogous diyne substrate was more rapid and a complete conversion was observed after 40 hours at room temperature. The cycloalkyne was isolated as a solid in 95% yield from which single crystals suitable for X-ray crystal structure determination was obtained. A rapid screening of catalysts and experimental conditions was undertaken to optimize the formation of cycloalkyne. A mechanistic proposal was also introduced for the cycloisomerization of diynes into cycloalkynes on the basis of the experimental observations.
- Odabachian, Yann,Le Goff, Xavier F.,Gagosz, Fabien
-
supporting information; scheme or table
p. 8966 - 8970
(2010/04/25)
-
- THERAPEUTIC COMPOUNDS
-
Substituted cinnamoyl anthranilate compounds exhibiting anti-fibrotic activity; or derivatives thereof, analogues thereof, pharmaceutically acceptable salts thereof, and metabolites thereof; with the proviso that the compound is not Tranilast.
- -
-
Page/Page column 75
(2008/06/13)
-