- Synthesis of biaryls using nickel-catalyzed [2+2+2] cocyclization
-
Methods of synthesizing biaryls using nickel-catalyzed [2+2+2] cocyclization were developed. Two ways for the synthesis of biaryl using [2+2+2] cocyclization were investigated: one method is that biaryls synthesized from alkyne having a phenyl group and 2
- Sato, Yoshihiro,Ohashi, Kenji,Mori, Miwako
-
-
Read Online
- Umpolung Strategy for Arene C?H Etherification Leading to Functionalized Chromanes Enabled by I(III) N-Ligated Hypervalent Iodine Reagents
-
The direct formation of aryl C?O bonds via the intramolecular dehydrogenative coupling of a C?H bond and a pendant alcohol represents a powerful synthetic transformation. Herein, we report a method for intramolecular arene C?H etherification via an umpoled alcohol cyclization mediated by an I(III) N-HVI reagent. This approach provides access to functionalized chromane scaffolds from primary, secondary and tertiary alcohols via a cascade cyclization-iodonium salt formation, the latter providing a versatile functional handle for downstream derivatization. Computational studies support initial formation of an umpoled O-intermediate via I(III) ligand exchange, followed by competitive direct and spirocyclization/1,2-shift pathways. (Figure presented.).
- Mikhael, Myriam,Guo, Wentao,Tantillo, Dean J.,Wengryniuk, Sarah E.
-
p. 4867 - 4875
(2021/09/14)
-
- Identification of small molecules blocking the pseudomonas aeruginosa type iii secretion system protein pcrv
-
Pseudomonas aeruginosa is an opportunistic bacterial pathogen that employs its type III secretion system (T3SS) during the acute phase of infection to translocate cytotoxins into the host cell cytoplasm to evade the immune system. The PcrV protein is located at the tip of the T3SS, facilitates the integration of pore-forming proteins into the eukaryotic cell membrane, and is required for translocation of cytotoxins into the host cell. In this study, we used surface plasmon resonance screening to identify small molecule binders of PcrV. A follow-up structure-activity relationship analysis resulted in PcrV binders that protect macrophages in a P. aeruginosa cell-based infection assay. Treatment of P. aeruginosa infections is challenging due to acquired, intrinsic, and adaptive resistance in addition to a broad arsenal of virulence systems such as the T3SS. Virulence blocking molecules targeting PcrV constitute valuable starting points for development of next generation antibacterials to treat infections caused by P. aeruginosa.
- Sundin, Charlotta,Saleeb, Michael,Spjut, Sara,Qin, Liena,Elofsson, Mikael
-
-
- Enantioselective Lactonization by π-Acid-Catalyzed Allylic Substitution: A Complement to π-Allylmetal Chemistry
-
Asymmetric allylic alkylation (AAA) is a powerful method for the formation of highly useful, non-racemic allylic compounds. Here we present a complementary enantioselective process that generates allylic lactones via π-acid catalysis. More specifically, a
- Aponick, Aaron,Kizhakkayil Mangadan, Arun Raj,Liu, Ji
-
supporting information
p. 22224 - 22229
(2021/09/09)
-
- Metal-Free Synthesis of 4-Chloroisocoumarins by TMSCl-Catalyzed NCS-Induced Chlorinative Annulation of 2-Alkynylaryloate Esters
-
4-Chloroisocoumarins can be conveniently prepared from 2-alkynylaryloate esters via the activation of alkynes by electrophilic chlorine, generated in situ from N-chlorosuccinimide (NCS) in the presence of 10 mol % trimethylsilyl chloride (TMSCl), which leads to 6-endo-dig-selective chlorinative annulation to give the desired products in moderate to quantitative yields. The procedure employs readily available reagents and can be conveniently carried out on a wide scope of substrates under mild conditions (0 °C to rt). Furthermore, the reaction is scalable for gram-scale preparation of 4-chloroisocoumarins. Additionally, 4-bromo- and 4-iodoisocoumarins can be prepared in moderate to good yields by replacing NCS with N-bromosuccinimide (NBS) and N-iodosuccinimide (NIS), respectively.
- Norseeda, Krissada,Chaisan, Nattawadee,Thongsornkleeb, Charnsak,Tummatorn, Jumreang,Ruchirawat, Somsak
-
p. 16222 - 16236
(2019/12/25)
-
- Metal-Free Regioselective Chloroazidation of Internal Alkynes
-
A metal-free, room temperature protocol for the regioselective chloroazidation of internal alkynes is disclosed. The reactions of internal alkynes with trimethylsilyl azide (TMSN3) in the presence of 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) afforded the corresponding chloroazidoalkenes in good yields. This reaction has good functional group tolerance and is operationally simple.
- Huang, Bin,Liffert, Raphael,Linden, Anthony,Gademann, Karl
-
supporting information
p. 981 - 984
(2019/01/04)
-
- Comparison between Conventional and Nonconventional Methods for the Synthesis of Some 2-Oxazolidinone Derivatives and Preliminary Investigation of Their Inhibitory Activity Against Certain Protein Kinases
-
A series of propargyl and allyl carbamates were prepared directly from propargyl and allyl alcohols and phenyl or cyclohexyl isocyanate or indirectly by generating the isocyanates in situ from the corresponding Cbz-protected amines. The obtained carbamate
- Ziane,Mazari,Safer,Sad El Hachemi Amar,Ruchaud,Baratte,Bach
-
p. 1061 - 1069
(2019/09/06)
-
- Catalytic Dehydrative Lactonization of Allylic Alcohols
-
A convenient strategy for the synthesis of phthalides and ?-butyrolactones is reported. The method utilizes readily prepared allylic alcohols in formal Au(I)- and Pd(II)-catalyzed SN2′ reactions. Using these catalysts, exclusive formation of the desired five-membered lactones is observed, completely avoiding the competing direct lactonization pathway that forms the undesired seven-membered ring with protic acids and alternative metal salts. This mild and operationally simple method notably tolerates exomethylene groups and should find use in both phthalide and terpene syntheses.
- Liu, Ji,Miotto, Romain J.,Segard, Julien,Erb, Ashley M.,Aponick, Aaron
-
supporting information
p. 3034 - 3038
(2018/05/28)
-
- Design and synthesis of novel xanthine derivatives as potent and selective A2B adenosine receptor antagonists for the treatment of chronic inflammatory airway diseases
-
Adenosine induces bronchial hyperresponsiveness and inflammation in asthmatics through activation of A2B adenosine receptor (A2BAdoR). Selective antagonists have been shown to attenuate airway reactivity and improve inflammatory cond
- Basu, Sujay,Barawkar, Dinesh A.,Ramdas, Vidya,Patel, Meena,Waman, Yogesh,Panmand, Anil,Kumar, Santosh,Thorat, Sachin,Naykodi, Minakshi,Goswami, Arnab,Reddy, B. Srinivasa,Prasad, Vandna,Chaturvedi, Sandhya,Quraishi, Azfar,Menon, Suraj,Paliwal, Shalini,Kulkarni, Abhay,Karande, Vikas,Ghosh, Indraneel,Mustafa, Syed,De, Siddhartha,Jain, Vaibhav,Banerjee, Ena Ray,Rouduri, Sreekanth R.,Palle, Venkata P.,Chugh, Anita,Mookhtiar, Kasim A.
-
p. 218 - 229
(2017/04/19)
-
- ISOQUINOLINONE DERIVATIVES USEFUL IN THE TREATMENT OF CANCER
-
The present invention relates to a compound of the following formula (I) or a pharmaceutically acceptable salt and/or solvate thereof, notably for use as a drug, notably in the treatment of cancer, as well as pharmaceutical compositions containing such a
- -
-
Page/Page column 24
(2016/03/19)
-
- γ-Lactone Synthesis via Palladium(II)-Catalyzed Lactonization of Unactivated Methylene C(sp3)-H Bonds
-
A palladium(II)-catalyzed intramolecular lactonization of unactivated methylene C(sp3)-H bonds using PIP bidentate auxiliary is described. This method provides an efficient and concise pathway to synthesize functionalized γ-lactones.
- Liu, Bin,Shi, Bing-Feng
-
supporting information
p. 2396 - 2400
(2016/09/28)
-
- ISOCHROMENE DERIVATIVES AS PHOSPHOINOSITIDE 3-KINASES INHIBITORS
-
The invention relates to compounds inhibiting phosphoinositide 3-kinases (PI3K), to pharmaceutical compositions comprising them and therapeutic use thereofin the treatment of disorders associated with PI3K enzymes.
- -
-
Page/Page column 65
(2015/07/07)
-
- ISOCHROMENE DERIVATIVES AS PHOSHOINOSITIDE 3-KINASES INHIBITORS
-
Compounds of formula (I) described herein are useful for inhibiting phosphoinositide 3-kinases (PI3K) and the treatment of disorders associated with PI3K enzymes.
- -
-
Paragraph 0552; 0553; 0554
(2015/06/24)
-
- Allenylphosphine oxides as simple scaffolds for phosphinoylindoles and phosphinoylisocoumarins
-
A range of phosphinoylindoles was prepared in one-pot from functionalized propargyl alcohols and a suitable P(III) precursor via a base-mediated reaction. The reaction proceeds via the intermediacy of allenylphosphine oxides. Similarly, phosphinoylisocoumarins were prepared from allenylphosphine oxides in a trifluoroacetic acid-mediated reaction; the latter also acts as a solvent. Interestingly, in the presence of wet trifluoroacetic acid, in addition to phosphinoylisocoumarins, phosphorus-free isocoumarins were also obtained. Key products were characterized by single crystal X-ray crystallography.
- Gangadhararao,Kotikalapudi, Ramesh,Reddy, M. Nagarjuna,Swamy Kumara
-
supporting information
p. 996 - 1005
(2014/05/20)
-
- Theoretical support for the involvement of a radical pathway in the formation of allenylzincs from propargyl iodides and dialkylzincs: Influence of zinc coordination
-
Propargyl iodides are good precursors for allenylzincs via reaction with diethylzinc, even in nondegassed medium. These reactions proceed via zinc/iodine exchange. Owing to the previously reported detection of propargyl radical by ESR experiments, in this process a radical mechanism was suspected. Calculations of the C-Zn BDEs in allenyl- and propargylzinc species were performed with the CBS-QB3 method to demonstrate that propargyl radicals could undergo homolytic substitution at zinc. The stabilization of allenylzinc derivatives by chelation, made possible by the selection of appropriate ortho-substituted 3-phenylalkynyl iodides as precursors, was shown to influence the regioselectivity of their addition to aldehydes and ketones. The more stabilized the chelated allenylzinc intermediate, the higher the ratio of homopropargylic alcohols.
- Jammi, Suribabu,Mouysset, Dominique,Siri, Didier,Bertrand, Michèle P.,Feray, Laurence
-
p. 1589 - 1603
(2013/04/10)
-
- ISOQUINOLINE COMPOUNDS AND METHODS FOR TREATING HIV
-
Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and their use for treating viral infections mediated by a member of the retrovirus family of viruses such as the Human Immunodeficiency Virus (HIV).
- -
-
Page/Page column 94
(2012/08/08)
-
- 5-Substituted isoquinoline derivatives
-
A compound represented by the following formula (1) or a salt thereof: wherein R1 represents hydrogen atom, a halogen atom and the like; R2 represents hydrogen atom, a halogen atom, a C1-6 alkyl group and the like; and R3 represents —O—X—C(A1)(A11)—C(A2)(A2l)—N(A3l)(A3)(X represents propylene group etc., A11 and A21 represent hydrogen atom, or a C1-6 alkyl group, A31 represents a C1-6 alkyl group substituted with hydroxyl group, or hydrogen atom, and A1, A2, and A3 represent hydrogen atom, a C1-6 alkyl group and the like) and the like, which has an inhibitory activity on the phosphorylation of myosin regulatory light chain, and is useful for treatment of diseases relating to contraction of various cells and the like.
- -
-
-
- SUBSTITUTED HYDROXYETHYLAMINE ASPARTYL PROTEASE INHIBITORS
-
The invention relates to novel compounds and also to methods of treating at least one disease, disorder, or condition associated with amyloidosis using such compounds. Amyloidosis refers to a collection of diseases, disorders, and conditions associated with abnormal deposition of A-beta protein.
- -
-
Page/Page column 242-243
(2008/06/13)
-
- On the diverse outcomes of base-induced cyclisations of 2-alkynylphenylhydroxamic acids
-
Base-induced cyclisations of 2-alkynylphenylhydroxamic acids occur by attack of nitrogen onto the alkyne group in either exo or endo fashions to give the corresponding isoindol-1(2H)-ones or 1(2H)-isoquinolinones depending upon the alkyne substituent.
- Knight, David W.,Lewis, Paul B.M.,Abdul Malik,Mshvidobadze, Elena V.,Vasilevsky, Sergei F.
-
p. 9187 - 9189
(2007/10/03)
-
- AMP deaminase inhibitors. 3. SAR of 3-(carboxyarylalkyl)coformycin aglycon analogues
-
N3-Substituted coformycin aglycon analogues with improved AMP deaminase (AMPDA) inhibitory potency are described. Replacement of the 5-carboxypentyl substituent in the lead AMPDA inhibitor 3-(5-carboxypentyl)-3,6,7,8- tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol (2) described in the previous article with various carboxyarylalkyl groups resulted in compounds with 10- 100-fold improved AMPDA inhibitory potencies. The optimal N3 substituent had m-carboxyphenyl with a two-carbon alkyl tether. For example, 3-[2-(3-carboxy- 5-ethylphenyl)ethyl]-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol (43g) inhibited human AMPDA with a K(i) = 0.06 μM. The compounds within the series also exhibited > 1000-fold specificity for AMPDA relative to adenosine deaminase.
- Kasibhatla, Srinivas Rao,Bookser, Brett C.,Probst, Gary,Appleman, James R.,Erion, Mark D.
-
p. 1508 - 1518
(2007/10/03)
-
- Heterocyclic compounds for the treatment of CNS and cardiovascular disorders
-
Novel aromatic bicyclic amines of formula (I) STR1 are useful in treating central nervous system disorders and cardiac arrhythmias and cardiac fibrillation.
- -
-
-
- Model studies of (+)-Bergenin: A convenient formation of aryl δ- lactones
-
The reaction of o-carboxyarylpropargyl bromides with aldehydes mediated by indium in aqueous medium conveniently generated aryl δ-lactones. The product formation was affected by the nature of the co-solvent.
- Hua, Xiao-Gang,Mague, Joel T.,Li, Chao-Jun
-
p. 6837 - 6840
(2007/10/03)
-