- Assemblies of 1,4-Bis(diarylamino)naphthalenes and Aromatic Amphiphiles: Highly Reducing Photoredox Catalysis in Water
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Host-guest assemblies of a designed 1,4-bis(diarylamino)naphthalene and V-shaped aromatic amphiphiles consisting of two pentamethylbenzene moieties bridged by an m -phenylene unit bearing two hydrophilic side chains emerged as highly reducing photoredox catalysis systems in water. An efficient demethoxylative hydrogen transfer of Weinreb amides has been developed. The present supramolecular strategy permits facile tuning of visible-light photoredox catalysis in water.
- Abe, Manabu,Akita, Munetaka,Chitose, Youhei,Hyodo, Yuki,Koike, Takashi,Takahashi, Keigo,Yoshizawa, Michito
-
supporting information
(2021/10/21)
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- ASPARAGINE DERIVATIVES AND METHODS OF USE THEREOF
-
The present invention relates to compounds of formulas (A) and (I), pharmaceutically acceptable salts thereof, and solvates of any of them, pharmaceutical compositions comprising them, methods of preparation thereof, intermediate compounds useful for the preparation thereof, and methods of treatment or prophylaxis of diseases, in particular cancer, such as colorectal cancer, using these. (A) (I)
- -
-
Paragraph 00472-00473
(2021/12/31)
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- Catalytic α-Deracemization of Ketones Enabled by Photoredox Deprotonation and Enantioselective Protonation
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This study reports the catalytic deracemization of ketones bearing stereocenters in the α-position in a single reaction via deprotonation, followed by enantioselective protonation. The principle of microscopic reversibility, which has previously rendered this strategy elusive, is overcome by a photoredox deprotonation through single electron transfer and subsequent hydrogen atom transfer (HAT). Specifically, the irradiation of racemic pyridylketones in the presence of a single photocatalyst and a tertiary amine provides nonracemic carbonyl compounds with up to 97% enantiomeric excess. The photocatalyst harvests the visible light, induces the redox process, and is responsible for the asymmetric induction, while the amine serves as a single electron donor, HAT reagent, and proton source. This conceptually simple light-driven strategy of coupling a photoredox deprotonation with a stereocontrolled protonation, in conjunction with an enrichment process, serves as a blueprint for other deracemizations of ubiquitous carbonyl compounds.
- Chen, Shuming,Gao, Anthony Z.,Ivlev, Sergei I.,Meggers, Eric,Nie, Xin,Ye, Chen-Xi,Zhang, Chenhao
-
supporting information
p. 13393 - 13400
(2021/09/03)
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- SMALL MOLECULE INHIBITORS OF ACETYL COENZYME A SYNTHETASE SHORT CHAIN 2 (ACSS2)
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The present invention relates to compounds of formula (I). The compounds may be used to modulate the acetyl coenzyme A synthetase short chain 2 (ACSS2) protein and may thereby treat, ameliorate or prevent a disease selected from cancer, bacterial infection, viral infection, parasitic infection, fungal infection, neurodegenerative disease, neurological disorder, cerebrovascular disease, cardiovascular disease, non- alcoholic fatty liver disease and obesity. Alternatively, or additionally, the compounds maybe used to promote healthy ageing.
- -
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Page/Page column 115; 116
(2021/01/29)
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- Iron-Catalyzed Enantioselective Radical Carboazidation and Diazidation of α,β-Unsaturated Carbonyl Compounds
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Azidation of alkenes is an efficient protocol to synthesize organic azides which are important structural motifs in organic synthesis. Enantioselective radical azidation, as a useful strategy to install a C-N3 bond, remains challenging due to the inherently instability and unique structure of radicals. Here, we disclose an efficient enantioselective radical carboazidation and diazidation of α,β-unsaturated ketones and amides catalyzed by chiral N,N′-dioxide/Fe(OTf)2 complexes. An array of substituted alkenes was transformed to the corresponding α-azido carbonyl derivatives in good to excellent enantioselectivities, benefiting the preparation of chiral α-amino ketones, vicinal amino alcohols, and vicinal diamines. Control experiments and mechanistic studies proved the radical pathway in the reaction process. The DFT calculations showed that the azido transferred to the radical intermediate via an intramolecular five-membered transition state with the internal nitrogen of the Fe-N3 species.
- Dong, Shunxi,Feng, Xiaoming,He, Jun,Liu, Wen,Liu, Xiaohua,Pu, Maoping,Wu, Yun-Dong,Zhang, Tinghui
-
supporting information
p. 11856 - 11863
(2021/08/16)
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- Blue Light-Promoted N?H Insertion of Carbazoles, Pyrazoles and 1,2,3-Triazoles into Aryldiazoacetates
-
Blue light irradiation of aryldiazoacetates leads to the formation of free carbenes, which can react with carbazoles, pyrazoles and 1,2,3-triazoles to afford the corresponding N?H inserted products. These reactions are performed under air and at room temperature, allowing the mild preparation of a variety of motifs found in biologically relevant targets. (Figure presented.).
- Stivanin, Mateus L.,Fernandes, Alessandra A. G.,da Silva, Amanda F.,Okada, Celso Y.,Jurberg, Igor D.
-
supporting information
p. 1106 - 1111
(2020/01/25)
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- Synthesis of various acylating agents directly from carboxylic acids
-
A straightforward synthesis of acylating reagents such as Weinreb and MAP amides from aromatic, aliphatic carboxylic acids, and amino acids using PPh3/NBS combination is described. A chemo-selective modification of the carboxylic acid group into Weinreb amide in the presence of more reactive aldehydes and ketones is presented. All reactions were performed at ambient temperature under air using undried commercial grade solvent. Furthermore, the present methodology could be performed at a gram scale under inert-free reaction conditions. In addition, 7-azaindoline amide auxiliary (used for catalytic asymmetric aldol- and Mannich-type reactions), which behaves like Weinreb amide is also synthesized under similar reaction conditions.
- Pilathottathil, Fathima,Vineet Kumar, Doppalapudi,Kaliyamoorthy, Alagiri
-
supporting information
p. 1622 - 1632
(2020/04/27)
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- An Efficient Palladium-Catalysed Aminocarbonylation of Benzyl Chlorides
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An improved procedure for the aminocarbonylation of benzyl chloride derivatives using carbon monoxide and either primary or secondary amines has been developed. Studying the competing background alkylation reaction allowed the solvent and base to be selected for a simple catalyst screen, which, in turn, enabled the discovery of a method for the preparation of 2-arylacetamides under mild conditions, with minimal side-products using an inexpensive phosphine ligand. This non-traditional optimisation strategy allowed us to overcome the background alkylation, which has been cited as justification for the development of more complex and less atom-economical approaches.
- Oram, Niall,Richardson, Jeffery,Rilvin-Derrick, Eloise
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p. 369 - 372
(2020/02/27)
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- A Unified Strategy for the Synthesis of Difluoromethyl- And Vinylfluoride-Containing Scaffolds
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Here, we report a general method for the synthesis of quaternary and tertiary difluoromethylated compounds and their vinylfluoride analogues. The strategy, which relies on a two-step sequence featuring a C-selective electrophilic difluoromethylation and either a palladium-catalyzed decarboxylative protonation or a Krapcho decarboxylation, is practical, scalable, and high yielding. Considering the generality of the method and the attractive properties offered by the difluoromethyl group, this approach provides a valuable tool for late-stage functionalization and drug development.
- Duchemin, Nicolas,Buccafusca, Roberto,Daumas, Marc,Ferey, Vincent,Arseniyadis, Stellios
-
supporting information
p. 8205 - 8210
(2019/10/16)
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- Enantioselective Addition of Alkynyl Ketones to Nitroolefins Assisted by Br?nsted Base/H-Bonding Catalysis
-
Various sets of enolizable alkynyl ketones (including methyl ynones with α-aryl, α-alkenyl, and α-alkoxy groups) were able to react smoothly with nitroolefins with the assistance of bifunctional Br?nsted base/H-bond catalysts to provide adducts with two consecutive tertiary stereocenters in a highly diastereo- and enantioselective fashion. Further transformation of the obtained adducts into optically active acyclic and polycyclic molecules, including some with intricate carbon skeletons, was also demonstrated.
- Campano, Teresa E.,Iriarte, Igor,Olaizola, Olatz,Etxabe, Julen,Mielgo, Antonia,Ganboa, I?aki,Odriozola, José M.,García, Jesús M.,Oiarbide, Mikel,Palomo, Claudio
-
supporting information
p. 4390 - 4397
(2019/03/07)
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- Formamide catalyzed activation of carboxylic acids-versatile and cost-efficient amidation and esterification
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A novel, broadly applicable method for amide C-N and ester C-O bond formation is presented based on formylpyrrolidine (FPyr) as a Lewis base catalyst. Herein, trichlorotriazine (TCT), which is the most cost-efficient reagent for OH-group activation, was employed in amounts of ≤40 mol% with respect to the starting material (100 mol%). The new approach is distinguished by excellent cost-efficiency, waste-balance (E-factor down to 3) and scalability (up to >80 g). Moreover, high levels of functional group compatibility, which includes acid-labile acetals and silyl ethers, are demonstrated and even peptide C-N bonds can be formed. In comparison to reported amidation procedures using TCT, yields are considerably improved (for instance from 26 to 91%) and esterification is facilitated for the first time in synthetically useful yields. These significant enhancements are rationalized by activation by means of acid chlorides instead of less electrophilic acid anhydride intermediates.
- Huy, Peter H.,Mbouhom, Christelle
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p. 7399 - 7406
(2019/08/20)
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- Ruthenium-Catalyzed Oxidative Amidation of Alkynes to Amides
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Complex CpRuCl(PPh3)2 catalyzes reactions of terminal alkynes with 4-picoline N-oxide and primary and secondary amines to afford the corresponding amides. The reactions occur in chlorinated solvent and aqueous medium, showing applications in peptide chemistry. Stoichiometric studies reveal that the true catalysts of the processes are the vinylidene cations [CpRu(=C=CHR)(PPh3)2]+ which are oxidized to the Ru(η2-CO)-ketenes by the N-oxide. Finally, nucleophilic additions of primary and secondary amines to the free ketenes yield the corresponding amides.
- álvarez-Pérez, Andrea,Esteruelas, Miguel A.,Izquierdo, Susana,Varela, Jesús A.,Saá, Carlos
-
supporting information
p. 5346 - 5350
(2019/07/08)
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- A method of preparing intermediates of luck sha neiwei
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The invention provides a preparation method for a fosamprenir intermediate. The preparation method comprises the following steps: taking benzyl cyanide as a raw material, and performing steps of nitrile hydrolysis, acylation, reaction with a Grignard reagent, ammonization, cyclizing and the like for synthesizing (2R,3S)-1,2-epoxy-3-t-butyloxycarborylamino-4-phenyl butane. The method is reasonable in process, simple to operate, low in cost and high in yield; with the method, industrialization can be well realized and the production efficiency is improved.
- -
-
Paragraph 0045; 0046; 0053; 0060
(2018/03/26)
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- Iron-Catalyzed Synthesis of Tetrahydronaphthalenes via 3,4-Dihydro-2H-pyran Intermediates
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The development of an iron(III)-catalyzed synthetic strategy toward functionalized tetrahydronaphthalenes is described. This approach is characterized by its operational simplicity and is distinct from currently available procedures that rely on [4 + 2]-cycloadditions. Our strategy takes advantage of the divergent reactivity observed for simple aryl ketone precursors to gain exclusive access to tetrahydronaphthalene products (23 examples). Detailed mechanistic investigations identified pyrans as reactive intermediates that afford the desired tetrahydronaphthalenes in high yields upon iron(III)-catalyzed Friedel-Crafts alkylation.
- Watson, Rebecca B.,Schindler, Corinna S.
-
supporting information
p. 68 - 71
(2018/01/17)
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- Strategy for Overcoming Full Reversibility of Intermolecular Radical Addition to Aldehydes: Tandem C-H and C-O Bonds Cleaving Cyclization of (Phenoxymethyl)arenes with Carbonyls to Benzofurans
-
An intermolecular addition of carbon radicals enabled by a cascade radical coupling strategy is developed. It includes an intermolecular alkyl radical addition to a carbonyl group followed by an intramolecular alkoxy radical addition to haloarenes and produces substituted benzofurans in high yields. The radical nature of this reaction is explored by radical trapping experiments and EPR analysis. The mechanism is investigated by KIE experiments and control experiments. This method could provide rapid and practical access to the key intermediate of TAM-16, a safe and potent antibacterial agent for treating tuberculosis, and, therefore, is of great importance for organic synthesis and the pharmaceutical industry.
- Zheng, Hong-Xing,Shan, Xiang-Huan,Qu, Jian-Ping,Kang, Yan-Biao
-
supporting information
p. 3310 - 3313
(2018/06/11)
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- Highly Regioselective and E/ Z-Selective Hydroalkylation of Ynone, Ynoate, and Ynamide via Photoredox Mediated Ni/Ir Dual Catalysis
-
Exclusively α- and highly E/Z-selective hydroalkylation of ynone, ynoate, and ynamide was achieved via photoredox mediated Ni/Ir dual catalysis with high atom and step economy, producing trisubstituted enones, which are versatile synthetic building blocks. The developed reaction selectively delivered the α/Z isomer, which is complementary to the previously reported β-alkylation processes. The trisubstituted enones could be transformed to more valuable compounds via post-functionalization.
- Go, Su Yong,Lee, Geun Seok,Hong, Soon Hyeok
-
supporting information
p. 4691 - 4694
(2018/08/09)
-
- Structure-Based Drug Design of Mineralocorticoid Receptor Antagonists to Explore Oxosteroid Receptor Selectivity
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The mineralocorticoid receptor (MR) is a nuclear hormone receptor involved in the regulation of body fluid and electrolyte homeostasis. In this study we explore selectivity triggers for a series of nonsteroidal MR antagonists to improve selectivity over other members of the oxosteroid receptor family. A biaryl sulfonamide compound was identified in a high-throughput screening (HTS) campaign. The compound bound to MR with pKi=6.6, but displayed poor selectivity over the glucocorticoid receptor (GR) and the progesterone receptor (PR). Following X-ray crystallography of MR in complex with the HTS hit, a compound library was designed that explored an induced-fit hypothesis that required movement of the Met852 side chain. An improvement in MR selectivity of 11- to 79-fold over PR and 23- to 234-fold over GR was obtained. Given the U-shaped binding conformation, macrocyclizations were explored, yielding a macrocycle that bound to MR with pKi=7.3. Two protein–ligand X-ray structures were determined, confirming the hypothesized binding mode for the designed compounds.
- Nordqvist, Anneli,O'Mahony, Gavin,Fridén-Saxin, Maria,Fredenwall, Marlene,Hogner, Anders,Granberg, Kenneth L.,Aagaard, Anna,B?ckstr?m, Stefan,Gunnarsson, Anders,Kaminski, Tim,Xue, Yafeng,Dellsén, Anita,Hansson, Eva,Hansson, Pia,Ivarsson, Ida,Karlsson, Ulla,Bamberg, Krister,Hermansson, Majlis,Georgsson, Jennie,Lindmark, Bo,Edman, Karl
-
supporting information
p. 50 - 65
(2017/01/17)
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- Stereoselective synthesis of 2-aryl-4-en-1-ols, promising synthons for the preparation of oxygen heterocycles
-
Reactions of arylacetic acids with N-methoxymethanamine afford corresponding Weinreb amides which at alkenylation with methallyl and prenyl bromides in the presence of (Me3Si)2N–Na+ form unsaturated amides ArCHRCONMe(OMe) (R = CH2CMe=CH2, CH2C=CMe2). Amides readily react with BuLi and BnMgCl to give ketones ArCHRCOR' (R' = Bu, Bn). A stereoselective reduction of the latter with LiBH(s-Bu)3 leads to a quantitative formation of syn-isomers of 2-aryl-4-en-1-ols.
- Boev,Moskalenko,Belopukhov,Nikonova
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p. 169 - 177
(2017/04/21)
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- CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate or pharmaceutical composition comprising the same. From one aspect, the invention relates to an antibody-drug-conjugate (ADC) comprising an antibody consisting of the Trastuzumab or a biosimilar thereof, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment of cancer comprising administering to the subject an effective amount of said antibody-drug-conjugate or composition comprising the same.
- -
-
Paragraph 0251; 0252
(2017/05/15)
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- COMPOSITION FOR THE TREATMENT OF IGF-1R EXPRESSING CANCER
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The present invention relates to a method for the treatment of IGF-IR expressing cancers as well as to a compositions and a kit for said traitment. From one aspect, the invention reates to the combined use of a first antibody for the determination of the IGF-IR status of a cancer and a second antibody used as an ADC for the treatment of said cancer.
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Page/Page column 1078
(2017/05/17)
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- Enantioselective Mannich Reaction Employing 1,3,5-Triaryl-1,3,5-triazinanes Catalyzed by Chiral-at-Metal Rhodium Complexes
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Chiral-at-metal RhIII complexes catalyze the efficient enantioselective Mannich reaction of 2-acyl imidazoles with 1,3,5-triazinanes, affording the corresponding adducts in 81–99 % yield with up to >99 % enantioselectivity. This protocol performs with 0.1 mol-% of RhIII complex on gram scale without any loss in enantioselectivity.
- Gong, Jun,Li, Shi-Wu,Qurban, Saira,Kang, Qiang
-
supporting information
p. 3584 - 3593
(2017/07/22)
-
- Iron-Catalyzed Michael Addition of Ketones to Polar Olefins
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The base metal complex tetrabutylammonium nitrosyltricarbonylferrate {Bu4N[Fe(CO)3(NO)] (TBA[Fe])} – catalyzes the conjugate addition of ketones to polar olefins. The reaction is applicable to a wide range of substrates leading to interesting building blocks for organic synthesis. Clear indications for an acid-base type rather than a C?H activation pathway exist. (Figure presented.).
- Zhang, Di-Han,Knelles, Jakob,Plietker, Bernd
-
supporting information
p. 2469 - 2479
(2016/08/16)
-
- CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER
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The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody consisting of the Trastuzumab, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
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Page/Page column 35-36
(2016/11/17)
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- Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP)
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C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD+ as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50 = 0.24 μM). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50 = 0.18 μM) and 3-chloro- (IC50 = 0.17 μM) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer.
- Korwar, Sudha,Morris, Benjamin L.,Parikh, Hardik I.,Coover, Robert A.,Doughty, Tyler W.,Love, Ian M.,Hilbert, Brendan J.,Royer, William E.,Kellogg, Glen E.,Grossman, Steven R.,Ellis, Keith C.
-
p. 2707 - 2715
(2016/06/08)
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- Sterically Demanding Oxidative Amidation of α-Substituted Malononitriles with Amines Using O2
-
An efficient amidation method between readily available 1,1-dicyanoalkanes and either chiral or nonchiral amines was realized simply with molecular oxygen and a carbonate base. This oxidative protocol can be applied to both sterically and electronically challenging substrates in a highly chemoselective, practical, and rapid manner. The use of cyclopropyl and thioether substrates support the radical formation of α-peroxy malononitrile species, which can cyclize to dioxiranes that can monooxygenate malononitrile α-carbanions to afford activated acyl cyanides capable of reacting with amine nucleophiles.
- Li, Jing,Lear, Martin J.,Hayashi, Yujiro
-
supporting information
p. 9060 - 9064
(2016/07/26)
-
- Synthesis of Polysubstituted γ-Butenolides via a Radical Pathway: Cyclization of α-Bromo Aluminium Acetals and Comparison with the Cyclization of α-Bromoesters at High Temperature
-
Polysubstituted butenolides were obtained in good to high yields from α-bromoesters derived from propargyl alcohols by a one-pot reaction involving the radical cyclization of α-bromo aluminium acetals, followed by the oxidation of the resulting cyclic aluminium acetals in an Oppenauer-type process and migration of the exocyclic C-C bond into the α,β-position. Comparison with the direct cyclization of α-bromoesters at high temperature and under high dilution conditions is described. Deuterium-labelling experiments allowed us to uncover "invisible" 1,5-hydrogen atom transfers (1,5-HATs) that occur during these cyclization processes, together with the consequences of the latter in the epimerization of stereogenic centres. Compared to the classical approach, the cyclization of aluminium acetals proved to be highly chemoselective and its efficiency was illustrated by the short total syntheses of optically enriched γ-butenolides isolated from Plagiomnium undulatum and from Kyrtuhrix maculans.
- Bénéteau, Romain,Despiau, Carole F.,Rouaud, Jean-Christophe,Boussonnière, Anne,Silvestre, Virginie,Lebreton, Jacques,Dénès, Fabrice
-
supporting information
p. 11378 - 11386
(2015/08/03)
-
- Enantioselective Synthesis of syn-α-Aryl-β-hydroxy Weinreb Amides: Catalytic Asymmetric Roskamp Reaction of α-Aryl Diazo Weinreb Amides
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A convenient one-pot procedure to synthesize a variety of highly optically active syn-α-aryl-β-hydroxy Weinreb amides using an asymmetric Roskamp/reduction strategy is described. An oxazaborolidinium ion catalyzed asymmetric Roskamp reaction of α-aryl diazo Weinreb amides with aldehydes produced α-phenyl-β-keto Weinreb amides, which were in situ reduced with zinc borohydride to give syn-α-aryl-β-hydroxy Weinreb amides in good yields (up to 87%) with high enantioselectivities (up to 99% ee) and syn stereoselectivities (>20:1).
- Shin, Sung Ho,Baek, Eun Hee,Hwang, Geum-Sook,Ryu, Do Hyun
-
supporting information
p. 4746 - 4749
(2015/10/12)
-
- IGF-1R ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
-
The present invention relates to an antibody-drug-conjugate capable of binding IGF-1R. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to IGF-1R, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug- conjugate for the treatment of cancer.
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Page/Page column 105
(2015/11/16)
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- ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
-
The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to a Target, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
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Page/Page column 126
(2015/11/10)
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- Aerobic Asymmetric Dehydrogenative Cross-Coupling between Two C sp 3 -H Groups Catalyzed by a Chiral-at-Metal Rhodium Complex
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A sustainable C-C bond formation is merged with the catalytic asymmetric generation of one or two stereocenters. The introduced catalytic asymmetric cross-coupling of two Csp3-H groups with molecular oxygen as the oxidant profits from the oxidative robustness of a chiral-at-metal rhodium(III) catalyst and exploits an autoxidation mechanism or visible-light photosensitized oxidation. In the latter case, the catalyst serves a dual function, namely as a chiral Lewis acid for catalyzing enantioselective enolate chemistry and at the same time as a visible-light-driven photoredox catalyst. Green stuff: A sustainable C-C bond formation is merged with the catalytic asymmetric generation of one or two stereocenters by combining asymmetric enolate chemistry with either autoxidation or visible-light photosensitized oxidation. The robustness of a chiral-at-metal rhodium(III) catalyst serves to facilitate the reaction. PMP=para-methoxyphenyl, TFA=trifluoroacetic acid.
- Tan, Yuqi,Yuan, Wei,Gong, Lei,Meggers, Eric
-
supporting information
p. 13045 - 13048
(2015/11/02)
-
- Copper-catalyzed synthesis of weinreb amides by oxidative amidation of alcohols
-
A simple and efficient protocol has been developed for the oxidative amidation of alcohols to Weinreb amides using tert-butyl hydroperoxide as an oxidant and an inexpensive and air stable copper catalyst. The present protocol is advantageous as it uses commercially affordable alcohols as starting materials. The developed protocol also tolerates various substituted alcohols as starting materials to provide good to excellent yields of the desired products.
- Yedage, Subhash L.,Bhanage, Bhalchandra M.
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p. 526 - 532
(2015/02/19)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
-
The present invention concerns a compound of following formula (I): where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: ■ a straight-chain or branched, saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms substituted by one or more groups chosen from among OH and NR5R6, ■ -(CH2CH2X1)(CH2CH2X2)a2(CH2CH2X3)a3(CH2CH2X4)a4(CH2CH2X5)a5R7, ■ an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or ■ a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 28; 29
(2014/11/13)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
-
The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 22
(2014/11/13)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
-
The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: - an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or - a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 25
(2014/11/13)
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- Peptidyl cyclopropenones: Reversible inhibitors, irreversible inhibitors, or substrates of cysteine proteases?
-
Peptidyl cyclopropenones were previously introduced as selective cysteine protease reversible inhibitors. In the present study we synthesized one such peptidyl cyclopropenone and investigated its interaction with papain, a prototype cysteine protease. A set of kinetics, biochemical, HPLC, MS, and 13C-NMR experiments revealed that the peptidyl cyclopropenone was an irreversible inhibitor of the enzyme, alkylating the catalytic cysteine. In parallel, this cyclopropenone also behaved as an alternative substrate of the enzyme, providing a product that was tentatively suggested to be either a spiroepoxy cyclopropanone or a gamma-lactone. Thus, a single family of compounds exhibits an unusual variety of activities, being reversible inhibitors, irreversible inhibitors and alternative substrates towards enzymes of the same family.
- Cohen, Meital,Bretler, Uriel,Albeck, Amnon
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p. 788 - 799
(2013/09/02)
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- Amide formation using in situ activation of carboxylic acids with [Et 2NSF2]BF4
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The formation of amides through the in situ activation of carboxylic acids with [Et2NSF2]BF4 is presented. A wide range of carboxylic acids and amines were used to produce the corresponding amides in up to 99 % yield. The reaction of hindered amines was also possible in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) under slightly modified conditions. An enantiopure carboxylic acid and amine were both shown to react without racemization. Copyright
- Mahe, Olivier,Desroches, Justine,Paquin, Jean-Francois
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p. 4325 - 4331
(2013/07/26)
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- Highly stereoselective cyclopropanation of α,β-unsaturated carbonyl compounds with methyl (diazoacetoxy)acetate catalyzed by a chiral ruthenium(II) complex
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Tantalizing triangles: The title reaction gives bicarbonyl cyclopropane products that can lead to versatile intermediates with high yields and stereoselectivities. This system was also applied to the enantioselective total synthesis of spiro cyclopropane oxindole, an HIV-1 nonnucleoside reverse transcriptase inhibitor. Copyright
- Chanthamath, Soda,Takaki, Suguru,Shibatomi, Kazutaka,Iwasa, Seiji
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supporting information
p. 5818 - 5821
(2013/07/11)
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- A Weinreb amide approach to the synthesis of trifluoromethylketones
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A novel route to access trifluoromethylketones (TFMKs) from Weinreb amides is reported. This represents the first documented case of the Ruppert-Prakash reagent (TMS-CF3) reacting in a constructive manner with an amide and enables synthesis of TMFKs without risk of over-trifluoromethylation.
- Rudzinski, Diandra M.,Kelly, Christopher B.,Leadbeater, Nicholas E.
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supporting information
p. 9610 - 9612
(2012/10/29)
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- 3-alkoxy-1,2-dioxolanes: Synthesis and evaluation as potential antimalarial agents
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A number of 3-alkoxy-1,2-dioxolanes exhibit promising levels of antimalarial activity against Plasmodium falciparum. A new route to the 1,2-dioxolane core is reported based on tandem peroxidation/cyclization of enones.
- Schiaffo, Charles E.,Rottman, Matthias,Wittlin, Sergio,Dussault, Patrick H.
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scheme or table
p. 316 - 319
(2011/06/19)
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- NOVEL DIHYDROPYRIMIDIN-2(1H)-ONE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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The present invention is directed to novel dihydropyrimidin-2(1H)-one compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.
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Page/Page column 140
(2011/04/24)
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- ANTIHISTAMINIC PIPERIDINE DERIVATIVES AND INTERMEDIATES FOR THE PREPARATION THEREOF
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This invention relates to novel piperidine derivatives of formula (I) and a process for the preparation thereof, wherein R1 is H or C1-C6alkyl wherein the C1-C6alkyl moiety is straight or branched; R2 is -COOH or -COOalkyl wherein the alkyl moiety has from 1 to 6 carbon atoms and is straight or branched; or stereoisomers or pharmaceutically acceptable acid addition salt thereof.
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Page/Page column 23
(2010/11/03)
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- Palladium-catalyzed asymmetric allylic alkylation of 2-acylimidazoles as ester enolate equivalents
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A broad range of highly enantioenriched 2-acylimidazoles are synthesized by palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA) of 2-imidazolo-substituted enol carbonates. The enantioenriched 2-acylimidazole products can easily be converted to the corresponding carboxylic acid, ester, amide, and ketone derivatives with complete retention of the enantiopurity. The synthetic utility of this new method is demonstrated in the short, efficient synthesis of cetiedil.
- Trost, Barry M.,Lehr, Konrad,Michaelis, David J.,Xu, Jiayi,Buckl, Andreas K.
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supporting information; experimental part
p. 8915 - 8917
(2010/08/22)
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- Chemistry around imidazopyrazine and ibuprofen: Discovery of novel fatty acid amide hydrolase (FAAH) inhibitors
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Based on the imidazo-[1,2-a]-pyrazin-3-(7H)-one scaffold, a dual action prodrug has been designed for combining antioxidant and anti-inflammatory activities, possibly unmasked upon oxidation. The construction of the target-molecule requires two building blocks, namely a 2-amino-1,4-pyrazine and a 2-ketoaldehyde. Attempts to synthesize the 2-ketoaldehyde (5a) derived from ibuprofen failed, but led to the corresponding 2-ketoaldoxime (7a) which could not be condensed with the pyrazine synthons. However, a model compound, i.e. phenylglyoxal aldoxime, reacted well under microwave activation to furnish novel imidazo[1,2-a]-pyrazine-3-(7H)-imine derivatives (18a,b). These heterobicycles behave as antioxidants by inhibiting the lipid peroxidation, and one compound (18b) is endowed with a significant anti-inflammatory effect in a cellular test. Unexpectedly, all the synthetic intermediates derived from ibuprofen are good inhibitors of FAAH, the most active compound (4a) featuring the 1,3-dithian-2-yl motif.
- De Wael, Frédéric,Muccioli, Giulio G.,Lambert, Didier M.,Sergent, Thérse,Schneider, Yves-Jacques,Rees, Jean-Franois,Marchand-Brynaert, Jacqueline
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experimental part
p. 3564 - 3574
(2010/09/14)
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- INHIBITORS OF AKT ACTIVITY
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The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.
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Page/Page column 73
(2010/08/09)
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- A powerful reagent for synthesis of weinreb amides directly from carboxylic acids
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A powerful reagent, P[NCH3(OCH3)]3 (3), for conversion of carboxylic acids directly to Weinreb amides was developed. In most cases the yields of the corresponding Weinreb amides were above 90% when P[NCH3(OCHsu
- Niu, Teng,Zhang, Weiming,Huang, Danfeng,Xu, Changming,Wang, Haifeng,Hu, Yulai
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scheme or table
p. 4474 - 4477
(2009/12/24)
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- SUBSTITUTED-ARYL-2-PHENYLETHYL-1H-IMIDAZOLE COMPOUNDS AS SUBTYPE SELECTIVE MODULATORS OF ALPHA 2B AND/OR ALPHA 2C ADRENERGIC RECEPTORS
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A compound having selective modulating activity at the alpha 2B and/or alpha 2C adrenergic receptor subtypes is represented by the general Formula 1: wherein n=1-4; X is C or N; R1—R6 can be the same or different and are independently selected from the group consisting of H, C1-6 alkyl, OCH3, OH, F, Cl, Br, CH2OH, CH2N(R7)2, C(O)R8, CH2CN, CF3; wherein R7 is H or C1-6 alkyl; and R8 is C1-6 alkyl or aryl. The compounds of Formula 1 can be incorporated in pharmaceutical compositions and used in methods of treatment of alpha 2 receptor mediated diseases and conditions.
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Page/Page column 9
(2009/07/18)
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- Synthesis and evaluation of novel pyrazolidinone analogs of PGE2 as EP2 and EP4 receptors agonists
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Replacement of the hydroxy cyclopentanone ring in PGE2 with chemically more stable heterocyclic rings and substitution of the unsaturated α-alkenyl chain with a metabolically more stable phenethyl chain led to the development of potent and selective analogs of PGE2. Compound 10f showed the highest potency and selectivity for EP4 the receptor.
- Zhao, Zhong,Araldi, Gian Luca,Xiao, Yufang,Reddy, Adulla P.,Liao, Yihua,Karra, Srinivasa,Brugger, Nadia,Fischer, David,Palmer, Elizabeth
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p. 6572 - 6575
(2008/09/16)
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- Total synthesis of dolastatin 10 through ruthenium-catalyzed asymmetric hydrogenations
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A total synthesis of dolastatin 10, a potent inhibitor of microtubule assembly, which displayed remarkable antineoplastic activity, is reported. Our synthetic approach was based upon ruthenium-promoted asymmetric hydrogenation of β-keto esters derived from (S)-Boc-proline and (S)-Boc-isoleucine for the construction of the two key units: (2R,3R)-Boc-dolaproine (Dap) and (3R)-Boc-dolaisoleucine (Dil).
- Mordant, Céline,Reymond, Sébastien,Tone, Hitoshi,Lavergne, Damien,Touati, Ridha,Ben Hassine, Bechir,Ratovelomanana-Vidal, Virginie,Genet, Jean-Pierre
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p. 6115 - 6123
(2008/02/04)
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- HETEROCYCLIC KETONES AS NPY Y5 ANTAGONISTS
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This invention relates to heterocyclic ketones of formula (I) wherein R is C1-C6 alkyl, C1-C6 alkoxy, F, Br, Cl, and I; Ar is phenyl, naphthyl or thiophene; Ar is phenyl or pyridyl; X is C, N or S; I is 0 through 9; m is 2 through 7; n is 0, 1 or 2; p is 0, 1 or 2; and pharmaceutically acceptable salts thereof, useful in treating NPY Y5 receptor mediated conditions, and to novel intermediates and improved processes relating thereto.
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Page/Page column 14
(2010/11/24)
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- Synthesis of N-methoxy-N-methyl-β-enaminoketoesters: New synthetic precursors for the regioselective synthesis of heterocyclic compounds
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Weinreb amides react with the lithium or sodium acetylide of ethyl propynoate in a hitherto unexplored acyl substitution-conjugate addition sequence to furnish (E)-N-methoxy-N-methyl-β-enaminoketoesters. This approach provides a diverse entry to densely functionalized heterocyclic compounds, including pyrazoles through regioselective cyclocondensations with hydrazines in a microwave-assisted reaction.
- Persson, Tobias,Nielsen, John
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p. 3219 - 3222
(2007/10/03)
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