cas 2436-29-5, 3-(1,3-DIOXO-1,3-DIHYDRO-ISOINDOL-2-YL)-PROPIONALDEHYDE

Articles about 2436-29-5Total 56 be found

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Bott
p. 1304
(1969)
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Exploring endoperoxides as a new entry for the synthesis of branched azasugars
A new class of nitrogen-containing endoperoxides were synthesised by a photochemical [4 + 2]-cycloaddition between a diene and singlet oxygen. The endoperoxides were dihydroxylated and protected to provide a series of endoperoxide building blocks for organic synthesis, with potential use as precursors for the synthesis of branched azasugars. Preliminary exploration of the chemistry of these building blocks provided access to a variety of derivatives including tetrahydrofurans, epoxides and protected amino-tetraols.
Domeyer, Svenja,Bjerregaard, Mark,Johansson, Henrik,Pedersen, Daniel Sejer
p. 644 - 647
(2017)
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Divergent Stereocontrolled Synthesis of the Enantiopure Tetracyclic Cores of Asparagamine A and Stemofoline via an Intramolecular 2-Propylidine-1,3-(bis)silane Bicyclization
A concise and highly diastereoselective synthesis of the polyfused tetracyclic cores of the Stemona alkaloids asparagamine A and stemofoline that relies on a 2-propylidine-1,3-(bis)silane bicyclization onto a enantiodefined pyrrolidine 2,5-di(cation) equivalent derived from l-malic acid is reported. A crucial feature of this divergent synthetic approach involves the solvolysis of a transient and highly labile tertiary-propargylic hydroxylactam trifluoroacetate in the strongly ionizing medium 5 M LiClO4/Et2O. The acyliminium ion generated in this manner undergoes stereospecific interception by the aforementioned (bis)silane nucleophile.
Anderson, Bryon K.,Livinghouse, Tom
p. 9847 - 9855
(2015)
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Moe,Warner
p. 1251
(1949)
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Robust synthesis and crystal-structure analysis of 7-cyano-7-deazaguanine (PreQ0 base) and 7-(aminomethyl)-7-deazaguanine (PreQ1 base)
We describe robust and efficient synthetic methods for the synthesis of the preQ0 and preQ1 bases, which are the biosynthetic precursors of the hypermodified RNA nucleoside queuosine. The X-ray crystal-structure analysis of preQ1 is also described.
Klepper, Florian,Polborn, Kurt,Carell, Thomas
p. 2610 - 2616
(2005)
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Radical Carbonyl Umpolung Arylation via Dual Nickel Catalysis
The formation of carbon-carbon bonds lies at the heart of synthetic organic chemistry and is widely applied to construct complex drugs, polymers, and materials. Despite its importance, catalytic carbonyl arylation remains comparatively underdeveloped, due
Huang, Huan-Ming,Bellotti, Peter,Erchinger, Johannes E.,Paulisch, Tiffany O.,Glorius, Frank
supporting information
p. 1899 - 1909
(2022/02/01)

Cross-Selective Aza-Pinacol Coupling via Atom Transfer Catalysis
A cross-selective aza-pinacol coupling of aldehydes and imines has been developed to afford valuable β-amino alcohols. This strategy enables chemoselective conversion of aliphatic aldehydes to ketyl radicals, in the presence of more easily reduced imines and other functional groups. Upon carbonyl-specific activation by AcI, a photoinitiated Mn catalyst selectively reduces the resulting α-oxy iodide by an atom transfer mechanism. The ensuing ketyl radical selectively couples to imines, precluding homodimerization by a classical reductive approach. In this first example of reductive, ketyl coupling by atom transfer catalysis, Zn serves as a terminal reductant to facilitate Mn catalyst turnover. This new strategy also enables ketyl radical couplings to alkenes, alkynes, aldehydes, propellanes, and chiral imines.
Nagib, David A.,Rafferty, Sean M.,Rutherford, Joy E.,Wang, Lu,Zhang, Lumin
supporting information
p. 5622 - 5628
(2021/05/07)

Organocatalytic diastereo- And enantioselective oxa-hetero-Diels-Alder reactions of enones with aryl trifluoromethyl ketones for the synthesis of trifluoromethyl-substituted tetrahydropyrans
Tetrahydropyran derivatives are found in bioactives, and introduction of the trifluoromethyl group into molecules often improves biofunctions. Here we report diastereo- and enantioselective oxa-hetero-Diels-Alder reactions catalyzed by amine-based catalyst systems that afford trifluoromethyl-substituted tetrahydropyranones. Catalyst systems and conditions suitable for the reactions to provide the desired diastereomer products with high enantioselectivities were identified, and various trifluoromethyl-substituted tetrahydropyranones were synthesized with high diastereo- and enantioselectivities. Mechanistic investigation suggested that the reactions involve a [4 + 2] cycloaddition pathway, in which the enamine of the enone acts as the diene and the ketone carbonyl group of the aryl trifluoromethyl ketone acts as the dienophile. In this study, tetrahydropyran derivatives with the desired stereochemistry that are difficult to synthesize by previously reported methods were concisely obtained, and the range of tetrahydropyran derivatives that can be synthesized was expanded. This journal is
Pasha, Maira,Tanaka, Fujie
supporting information
p. 9242 - 9250
(2021/11/16)

Synthesis process of spermidine and intermediate thereof
The invention provides a synthesis process of spermidine (I) which takes 3 -t-butyloxycarbonyl V (N -) and -1-t-butyloxycarbonyl 4 - IV butanediamine (N -) as a raw material to obtain the spermidine trihydrochloride (-4 - II III) by reductive amination reaction, and provides a novel method for chemical synthesis of spermidine by liberation of the protecting group from the intermediate I (3 -) to obtain the spermidine (III) II.
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Paragraph 0027-0029

(2021/10/27)

Binuclear Pd(I)-Pd(I) Catalysis Assisted by Iodide Ligands for Selective Hydroformylation of Alkenes and Alkynes
Since its discovery in 1938, hydroformylation has been thoroughly investigated and broadly applied in industry (>107 metric ton yearly). However, the ability to precisely control its regioselectivity with well-established Rh- or Co-catalysts has thus far proven elusive, thereby limiting access to many synthetically valuable aldehydes. Pd-catalysts represent an appealing alternative, yet their use remains sparse due to undesired side-processes. Here, we report a highly selective and exceptionally active catalyst system that is driven by a novel activation strategy and features a unique Pd(I)-Pd(I) mechanism, involving an iodide-assisted binuclear step to release the product. This method enables β-selective hydroformylation of a large range of alkenes and alkynes, including sensitive starting materials. Its utility is demonstrated in the synthesis of antiobesity drug Rimonabant and anti-HIV agent PNU-32945. In a broader context, the new mechanistic understanding enables the development of other carbonylation reactions of high importance to chemical industry.
Zhang, Yang,Torker, Sebastian,Sigrist, Michel,Bregovi?, Nikola,Dydio, Pawe?
p. 18251 - 18265
(2020/11/02)

Experimental and computational evidence on gold-catalyzed regioselective hydration of phthalimido-protected propargylamines: An entry to β-amino ketones
The results of our investigations on the Au-catalyzed regioselective hydration reaction of both alkyl- A nd aryl-substituted N-propargyl phthalimides directed to the selective formation of the corresponding β-phthalimido ketones are described. Experimental data, in particular the observed regioselectivity, have been qualitatively supported by quantum-chemical calculations carried out on model systems in the framework of Density Functional Theory (DFT) followed by quantum theory of atoms in molecules (QTAIMS). Our results suggest that the electronic features of the initial adduct between the propargyl triple bond and the Au(i) catalyst, in particular the character of the gold-triple bond interaction, are essential for the observed regioselectivity. Other effects, such as the presence of the solvent and the formation of a H-bond between the water molecule and the phthalimido moiety, although apparently irrelevant for the regioselectivity, have proven to be kinetically and catalytically rather important. This journal is
Arcadi, Antonio,Aschi, Massimiliano,Marsicano, Vincenzo,Michelet, Véronique
p. 9438 - 9447
(2020/12/15)

Organocatalyzed Aerobic Oxidation of Aldehydes to Acids
The first example organocatalyzed aerobic oxidation of aldehydes to carboxylic acids in both organic solvent and water under mild conditions is developed. As low as 5 mol % N-hydroxyphthalimide was used as the organocatalyst, and molecular O2 was used as the sole oxidant. No transition metals or hazardous oxidants or cocatalysts were involved. A wide range of carboxylic acids bearing diverse functional groups were obtained from aldehydes, even from alcohols, in high yields.
Dai, Peng-Fei,Qu, Jian-Ping,Kang, Yan-Biao
supporting information
p. 1393 - 1396
(2019/02/26)

Supported Cobalt Nanoparticles for Hydroformylation Reactions
Hydroformylation of olefins has been studied in the presence of specific heterogeneous cobalt nanoparticles. The catalytic materials were prepared by pyrolysis of preformed cobalt complexes deposited onto different inorganic supports. Atomic absorption spectroscopy (AAS) measurements indicated a correlation of catalyst activity and cobalt leaching as well as a strong influence of the heterogeneous support on the productivity. These new, low-cost, easy-to-handle catalysts can substitute more toxic, unstable and volatile cobalt carbonyl complexes for hydroformylations on a laboratory scale.
Hertrich, Maximilian Franz,Scharnagl, Florian Korbinian,Pews-Davtyan, Anahit,Kreyenschulte, Carsten Robert,Lund, Henrik,Bartling, Stephan,Jackstell, Ralf,Beller, Matthias
supporting information
p. 5534 - 5538
(2019/03/26)

A Protocol to Transform Sulfones into Nitrones and Aldehydes
A simple method to transform sulfones into nitrones and therefore into the corresponding carbonyl derivatives has been developed. Some examples demonstrate that it is a new reliable and versatile reaction in the toolbox of sulfones that has great synthetic potential. NMR and computational studies were used to elucidate the mechanism.
Rodrigo, Eduardo,Alonso, Inés,Cid, M. Belén
supporting information

(2018/09/27)

A Protocol to Transform Sulfones into Nitrones and Aldehydes
A simple method to transform sulfones into nitrones and therefore into the corresponding carbonyl derivatives has been developed. Some examples demonstrate that it is a new reliable and versatile reaction in the toolbox of sulfones that has great synthetic potential. NMR and computational studies were used to elucidate the mechanism.
Rodrigo, Eduardo,Alonso, Inés,Cid, M. Belén
supporting information
p. 5789 - 5793
(2018/09/29)

Multicomponent Catalytic Asymmetric Synthesis of trans-Aziridines
A multicomponent trans-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl aldehydes than for aliphatic aldehydes. The key to the success with aryl aldehydes was allowing the catalyst, aldehyde, and amine to react for 20 min before addition of the diazo compound. A variety of 11 different electron-poor and electron-rich aryl aldehydes were screened to give trans-aziridines in 73-90% yield with 82-99% ee and trans/cis selectivities of 19:1 to >99:1. The optimal protocol for the trans-aziridination of aliphatic aldehydes did not require prereaction of the catalyst, aldehyde, and amine, and instead, the diazo compound could be added directly. The scope of the reaction is limited to unbranched aliphatic aldehydes and was tolerant of a number of functional groups including ethers, esters, epoxides, carbamates, and phthalimides. A total of 10 aliphatic aldehydes were examined and found to give trans-aziridines in 60-88% yield with 60-98% ee and trans/cis selectivities of 6:1 to >99:1. Alkenyl aldehydes did not react, but an alkynyl aldehyde gave a 71% yield and 95% ee of an aziridine that was found to be the cis- and not the trans-diastereomer. The aryl and aliphatic aldehydes both gave the trans-aziridines with the same absolute configuration with the same catalyst; however, in those cases where cis-aziridines were formed, the configuration was opposite for those formed from aryl versus aliphatic aldehydes.
Zhou, Yubai,Gupta, Anil K.,Mukherjee, Munmun,Zheng, Li,Wulff, William D.
p. 13121 - 13140
(2017/12/26)

Synthesis of β-Lactams by Palladium(0)-Catalyzed C(sp3)?H Carbamoylation
A general and user-friendly synthesis of β-lactams is reported that makes use of Pd0-catalyzed carbamoylation of C(sp3)?H bonds, and operates under stoichiometric carbon monoxide in a two-chamber reactor. This reaction is compatible with a range of primary, secondary and activated tertiary C?H bonds, in contrast to previous methods based on C(sp3)?H activation. In addition, the feasibility of an enantioselective version using a chiral phosphonite ligand is demonstrated. Finally, this method can be employed to synthesize valuable enantiopure free β-lactams and β-amino acids.
Dailler, David,Rocaboy, Ronan,Baudoin, Olivier
supporting information
p. 7218 - 7222
(2017/06/13)

Stereoselective Synthesis of Z Fluoroalkenes through Copper-Catalyzed Hydrodefluorination of gem-Difluoroalkenes with Water
A copper catalytic system was established for the stereoselective hydrodefluorination of gem-difluoroalkenes through C?F activation to synthesize various Z fluoroalkenes. H2O is used as the hydrogen source for the fluorine acceptor moiety. This mild catalytic system shows good-functional group compatibility, accepting a range of carbonyls as precursors to the gem-difluoroalkenes, including aliphatic, aromatic, and α,β-unsaturated aldehydes and even ketones. It serves as a powerful synthetic method for the late-stage modification of complex compounds.
Hu, Jiefeng,Han, Xiaowei,Yuan, Yu,Shi, Zhuangzhi
supporting information
p. 13342 - 13346
(2017/10/17)

Preparation method of pyrimidine derivatives
The invention provides a preparation method of pyrimidine derivatives, particularly a method for synthesizing compounds of which the structural formula is disclosed as Formula H. The compounds are (4-trifluoromethylpyrimidyl)-5-methylamine hydrochlorides. The new compounds can be used for development and screening of new drugs for treating diabetes, alopecia and various chronic diseases. The synthesis method is simple to operate, and has the advantages of high efficiency and low raw material cost. The synthesis route is simple and convenient in technique, and is suitable for scale-up production in factories.
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Paragraph 0050; 0051

(2017/06/02)

Tert-Butyl Nitrite: Organic Redox Cocatalyst for Aerobic Aldehyde-Selective Wacker-Tsuji Oxidation
An aldehyde-selective aerobic Wacker-Tsuji oxidation is developed. Using tert-butyl nitrite as a simple organic redox cocatalyst instead of copper or silver salts, a variety of aldehydes were achieved as major products in up to 30/1 regioselectivity as well as good to high yields at room temperature.
Ning, Xiao-Shan,Wang, Mei-Mei,Yao, Chuan-Zhi,Chen, Xian-Min,Kang, Yan-Biao
p. 2700 - 2703
(2016/06/15)

From in vitro to in cellulo: Structure-activity relationship of (2-nitrophenyl)methanol derivatives as inhibitors of PqsD in Pseudomonas aeruginosa
Recent studies have shown that compounds based on a (2-nitrophenyl)methanol scaffold are promising inhibitors of PqsD, a key enzyme of signal molecule biosynthesis in the cell-to-cell communication of Pseudomonas aeruginosa. The most promising molecule displayed anti-biofilm activity and a tight-binding mode of action. Herein, we report on the convenient synthesis and biochemical evaluation of a comprehensive series of (2-nitrophenyl)methanol derivatives. The in vitro potency of these inhibitors against recombinant PqsD as well as the effect of selected compounds on the production of the signal molecules HHQ and PQS in P. aeruginosa were examined. The gathered data allowed the establishment of a structure-activity relationship, which was used to design fluorescent inhibitors, and finally, led to the discovery of (2-nitrophenyl)methanol derivatives with improved in cellulo efficacy providing new perspectives towards the application of PqsD inhibitors as anti-infectives. This journal is the Partner Organisations 2014.
Storz, Michael P.,Allegretta, Giuseppe,Kirsch, Benjamin,Empting, Martin,Hartmann, Rolf W.
supporting information
p. 6094 - 6104
(2014/08/05)

Functional-group-tolerant, nickel-catalyzed cross-coupling reaction for enantioselective construction of tertiary methyl-bearing stereocenters
The first Negishi nickel-catalyzed stereospecific cross-coupling reaction of secondary benzylic esters is reported. A series of traceless directing groups is evaluated for ability to promote cross-coupling with dimethylzinc. Esters with a chelating thioether derived from commercially available 2-(methylthio)acetic acid are most effective. The products are formed in high yield and with excellent stereospecificity. A variety of functional groups are tolerated in the reaction including alkenes, alkynes, esters, amines, imides, and O-, S-, and N-heterocycles. The utility of this transformation is highlighted in the enantioselective synthesis of a retinoic acid receptor agonist and a fatty acid amide hydrolase inhibitor.
Wisniewska, Hanna M.,Swift, Elizabeth C.,Jarvo, Elizabeth R.
supporting information
p. 9083 - 9090
(2013/07/26)

Catalytic enantioselective formal Hetero-Diels-Alder reactions of enones with isatins to give spirooxindole tetrahydropyranones
Organocatalytic formal hetero-Diels-Alder reactions of enones with isatins, which gave highly enantiomerically enriched functionalized spirooxindole tetrahydropyranones via an enamine-based mechanism, were developed. The catalyst systems were identified by a screen of combinations of amines, acids, and additives. With the identified catalyst systems, various spirooxindole tetrahydropyranones were synthesized in high yields with high diastereo- and enantioselectivities (see scheme). Copyright
Cui, Hai-Lei,Tanaka, Fujie
supporting information
p. 6213 - 6216
(2013/07/04)

Rhodium catalyzed hydroformylation with formaldehyde and an external H 2-source
The efficiency of the syngas-free rhodium catalyzed hydroformylation of olefins with formaldehyde can be significantly improved by the addition of hydrogen gas or formic acid.
Uhlemann, Marcus,Doerfelt, Stephan,B?rner, Armin
p. 2209 - 2211
(2013/05/09)

Aldehyde-selective wacker-type oxidation of unbiased alkenes enabled by a nitrite co-catalyst
Breaking the rules: Reversal of the high Markovnikov selectivity of Wacker-type oxidations was accomplished using a nitrite co-catalyst. Unbiased aliphatic alkenes can be oxidized with high yield and aldehyde selectivity, and several functional groups are tolerated. 18O-labeling experiments indicate that the aldehydic O atom is derived from the nitrite salt. Copyright
Wickens, Zachary K.,Morandi, Bill,Grubbs, Robert H.
supporting information
p. 11257 - 11260
(2013/11/06)

MODULATORS OF HISTONE METHYLTRANSFERASE, AND METHODS OF USE THEREOF
Disclosed are compounds, pharmaceutical compositions containing the compounds, and the uses of the compounds and compositions as modulators of histone methyltransferases, and for treating diseases influenced by modulation of histone methyltransferase activity.
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(2012/06/30)

An excellent dual recycling strategy for the hypervalent iodine/nitroxyl radical mediated selective oxidation of alcohols to aldehydes and ketones
Using a recyclable hypervalent iodine reagent 1, the authors have constructed versatile and green methods for the hypervalent iodine and nitroxyl radical-mediated selective oxidation of alcohols to aldehydes and ketones. The recyclable reagent 1 having a unique tetraphenyladamantane structure exhibited almost the same reactivity as the ordinary reagent, phenyliodine diacetate (PIDA), in the hypervalent iodine(iii)/2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-mediated oxidation. For recycling, the reagent 1 could be nearly quantitatively recovered as the reduced tetraiodide 2 by filtration after reaction completion, utilizing the insolubility of the formed 2 in a polar solvent, specifically, methanol. Based on the confirmed reactivity and excellent recycling operation of the reagent 1, the methodology has been further extended to a greener dual recycling strategy. By combining the recyclable iodine reagent 1 and silica-supported TEPMO catalyst, a variety of alcohols were effectively oxidized to the desired aldehydes, and the two types of used reagent and catalyst, the iodine 1 and immobilized TEMPO 5, could be separately recovered by an easy workup, and both repeatedly used without any loss of their original activities for at least four cycles.
Dohi, Toshifumi,Fukushima, Kei-Ichiro,Kamitanaka, Tohru,Morimoto, Koji,Takenaga, Naoko,Kita, Yasuyuki
experimental part
p. 1493 - 1501
(2012/06/18)

New tetraphosphorus ligands for highly linear selective hydroformylation of allyl and vinyl derivatives
New tetraphosphorus ligands have been developed and applied in the rhodium-catalyzed regioselective hydroformylation of a variety of functionalized allyl and vinyl derivatives. Remarkably high linear selectivity was obtained by these tetraphosphorus ligands. The ligand that bears strong electron-withdrawing 2,4-difluorophenyl groups is the most effective one in affording linear aldehydes. The Rh/tetraphosphorus ligand catalyst is highly effective to produce linear aldehydes from functionalized allyl derivatives with heteroatoms or aromatic groups directly adjacent to the allyl group. For vinyl derivatives, the ligand is highly linear selective for acrylic derivatives, styrene, vinyl pyridine, and vinyl phthalimide. Linear to branch ratios of 26:1 and 10:1 were obtained for the hydroformylation of styrene and allyl cyanide, respectively. New tetraphosphorus ligands have been developed and applied in the rhodium-catalyzed regioselective hydroformylation of a variety of allyl and vinyl olefins (see scheme). Remarkably high linear selectivities were obtained by these ligands. Linear-to-branch ratios of 26:1 and 10:1 were obtained for the hydroformylation of styrene and allyl cyanide, respectively. Copyright
Cai, Chaoxian,Yu, Shichao,Cao, Bonan,Zhang, Xumu
experimental part
p. 9992 - 9998
(2012/09/07)

Process for Preparing Chiral Compounds
The present invention is directed to a 2-deoxyribose-5-phosphate aldolase (DERA) chemoenzymatic process for making chiral compounds.
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(2011/06/10)

Selective synthesis of gem -chlorofluorinated nitrogen-containing derivatives after superelectrophilic activation in superacid HF/SbF5
The first direct selective synthesis of novel gem-chlorofluorinated nitrogen-containing building blocks in superacid is reported. The dramatic role of the chlorine atom on the reaction is shown by in situ NMR experiments and allows the involvement of a novel original superelectrophilic activation process in superacid HF/SbF5 to be postulated.(Figure Presented)
Liu, Fei,Martin-Mingot, Agnes,Jouannetaud, Marie-Paule,Bachmann, Christian,Frapper, Gilles,Zunino, Fabien,Thibaudeau, Sebastien
supporting information; experimental part
p. 1460 - 1463
(2011/04/26)

Catalyst-controlled Wacker-type oxidation of protected allylic amines
On the contrary: Utilizing the [Pd-(quinox)]-TBHP catalyst system, protected allylic amines were oxidized with high selectivity for the methyl ketone product. This is contrary to the results obtained by the substrate-controlled Tsuji-Wacker oxidation, which highlights the catalyst-controlled system presented here (see scheme). A variety of N-pro-tecting groups undergo selective oxidation with high ketone selectivity. TBHP = tert-butylhydroperoxide.
Michel, Brian W.,McCombs, Jessica R.,Winkler, Andrea,Sigman, Matthew S.
supporting information; experimental part
p. 7312 - 7315
(2010/11/05)

Synthesis of novel rhodium phosphite catalysts for efficient and selective isomerization-hydroformylation reactions
New modular H8-BINOL-based phosphite ligands have been synthesized. High activity and regioselectivity has been achieved in the rhodium-catalyzed isomerization-hydroformylation of internal olefins. The active catalysts have been characterized by in situ NMR studies.
Piras, Irene,Jennerjahn, Reiko,Jackstell, Ralf,Baumann, Wolfgang,Spannenberg, Anke,Franke, Robert,Wiese, Klaus-Diether,Beller, Matthias
experimental part
p. 479 - 486
(2010/04/05)

A facile synthetic approach to 7-deazaguanine nucleosides via a boc protection strategy
An efficient route to the preparation of 5-substituted 2-amino-7-((2R,4R, 5R)-tetrahydro-4-hydroxy-5-(hydroxymethyl)furan-2-yl)-3H-pyrrolo[2,3- d]pyrimidin-4(7H)-one compounds has been developed by the condensation of ω-substituted aldehydes with 2,6-diaminopyrimidin-4(3H)-one, followed by Boc protection to afford the corresponding N2,N2,N 7-tris-Boc-O4-t-Bu-5-substituted 2-amino-3H-pyrrolo[2,3-d]pyrimidin- 4(7H)-one, which is amenable to direct condensation with 1-chloro-2-deoxy-3,5- di-O-p-toluoyl-r-D-erythro-pentofuranose. This route affords an efficient synthesis to 2-amino-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one, 2-amino-5-alkyl-3H- pyrrolo[2,3-d]pyrimidin-4(7H)-one, and guanine nucleosides.
Wang, Ruo-Wen,Gold, Barry
supporting information; experimental part
p. 2465 - 2468
(2009/10/18)

Lyzed isomerization and hydroformylation of olefins
The palladium-catalyzed hydroformylation of 1-octene has been studied in the presence of different phosphines and acid cocatalysts. The best results are achieved in the presence of in situ-generated palladium complexes with bidentate phosphines. It is demonstrated that the acid concentration is a crucial factor for obtaining high linear selectivity. A novel optimized catalyst based on an arylheteroarylphosphine has been applied for hydroformylation of different aliphatic and aromatic olefins. Good activity and excellent selectivity towards the linear aldehydes is achieved.
Jennerjahn, Reiko,Piras, Irene,Jackstell, Ralf,Franke, L Robert,Wiese, Klaus-Diether,Beller, Thias
experimental part
p. 6383 - 6388
(2010/01/16)

QUINAZOLINE DERIVATIVES AS A SIGNAL TRANSDUCTION INHIBITOR AND METHOD FOR THE PREPARATION THEREOF
The present invention relates to a novel quinazoline derivative and a pharmaceutically acceptable salt thereof as a signal transduction inhibitor, a method for the preparation thereof, and a pharmaceutical composition and a therapeutic composition comprising same as an active ingredient. The inventive quinazoline derivative as a signal transduction inhibitor can selectively and effectively inhibit diseases caused by the overactivity of a tyrosine kinase.
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(2010/11/27)

Asymmetric synthesis of highly substituted azapolycyclic compounds via 2-alkenyl sulfoximines: Potential scaffolds for peptide mimetics
The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to α- or β-amino aldehydes, followed by a Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted heterocycles. In addition to this methodological work, initial results on the biological activity of selected examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles in this context is discussed.
Reggelin, Michael,Junker, Bernd,Heinrich, Timo,Slavik, Stefan,Buehle, Philipp
p. 4023 - 4034
(2007/10/03)

Indole and benzimidazole derivatives
The present invention relates to new indole and benzimidazole compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds. The compounds of the invention have the following general formula:
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(2008/06/13)

THIAZOLIMINE COMPOUND AND OXAZOLIMINE COMPOUND
A compound represented by the formula (1): (wherein X represents sulfur or oxygen; R1 and R2 each represents a group represented by the formula -Y3-Z, etc.; Y3 represents a single bond or (un)substituted alkylene; Y1 and Y2 each represents (un)substituted alkylene; Z represents hydrogen, an (un)saturated monocyclic heterocyclic group, etc.; M represents carboxy, etc.; Q represents o-phenylene, etc.; and A represents an (un)saturated monocyclic hydrocarbon group, etc.), a prodrug thereof, or a pharmaceutically acceptable salt of either. They are compounds having chymase inhibitory activity and useful as a therapeutic agent for hypertension, cardiac failure, etc.
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(2010/11/08)

Substituted thiophene compounds as modulators of protein tyrosine phosphatases (PTPases)
The present invention provides novel compounds of formula 1a, novel compositions, methods of their use, and methods of their manufacture, where such compounds are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPase's) such as PTP1B, CD45, SHP-1, SHP-2, PTPα, LAR and HePTP or the like. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, immune dysfunctions including autoimmunity diseases with dysfunctions of the coagulation system, allergic diseases including asthma, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases.
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(2008/06/13)

Development of Irreversible Diphenyl Phosphonate Inhibitors for Urokinase Plasminogen Activator
In this letter we report the synthesis and biochemical evaluation of selective, irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator (uPA). A diphenyl phosphonate group was introduced on the substratelike peptide Z-D-Ser-Ala-Arg, and modification of the guanidine side chain was investigated. A guanylated benzyl group appeared the most promising side chain modification. A kapp value in the 103 M -1 s-1 range for uPA was obtained, together with a selectivity index higher than 240 toward other trypsin-like proteases such as tPA, thrombin, plasmin, and FXa.
Joossens,Van Der Veken,Lambeir,Augustyns,Haemers
p. 2411 - 2413
(2007/10/03)

Stereoselective synthesis of novel dipeptide β-turn mimetics targeting melanocortin peptide receptors
(Matrix presented) The novel dipeptide β-turn mimetic, 4,8-disubstituted azabicyclo[4.3.0]nonane amino acid ester (15), has been synthesized to serve as a peptide mimetic of the dipeptide Phe-Arg, which contains two important pharmacophore elements in melanotropin peptides. Introduction of side-chain functionality at C-8 was achieved by using β-functionalized pyroglutamate (8) as a synthetic precursor. The side chain at C-4 was introduced by bromination of dehydroamino acid intermediate (10) followed by Suzuki cross-coupling.
Zhang, Junyi,Xiong, Chiyi,Ying, Jinfa,Wang, Wei,Hruby, Victor J.
p. 3115 - 3118
(2007/10/03)

Free radical-mediated vinyl amination: A mild, general pyrrolidinyl enamine synthesis
The complete scope of free radical-mediated vinyl amination is described, using 5-exo-trig cyclizations of vinyl radicals to the nitrogen of azomethines. The focus is primarily on N,N-dialkyl enamines since their nucleophilicity renders them the most challenging enamines to synthesize using redox conditions. These studies establish several encouraging precedents for the broader application of this strategy.
Nugent, Benjamin M.,Williams, Amie L.,Prabhakaran,Johnston, Jeffrey N.
p. 8877 - 8888
(2007/10/03)

Fused and bridged bi- and tri-cyclic lactams via sequential metallo-azomethine ylide cycloaddition-lactamisation
Aldimines of α-amino esters derived from aldehydes bearing an α-, β- or γ-protected amino group undergo AgOAc/R3N catalysed cycloaddition to electronegative olefins (dipolarophile). Subsequent unmasking of the amino group and lactamisation, spontaneous in most cases, generates 5-7 membered fused and bridged bi- and tri-cyclic lactams. The regioselectivity of the lactamisation is controlled by appropriate choice of the dipolarophile.
Blaney, Paul,Grigg, Ronald,Rankovic, Zoran,Thornton-Pett, Mark,Xu, Juan
p. 1719 - 1737
(2007/10/03)

Racemic thioesters for production of polyketides
Facile methods for preparing diketide and triketide thioesters are disclosed. The resulting thioesters may be used as intermediates in the synthesis of desired polyketides, and may contain functional groups which ultimately reside in side chains on the resulting polyketide and thus can be used further to manipulate the polyketide so as form derivatives. The polyketides produced may also be tailored by glycosylation, hydroxylation and the like. New polyketides and their derivatives and tailored forms are thereby produced.
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(2008/06/13)

MODULATORS OF PROTEIN TYROSINE PHOSPHATASES (PTPASES)
The present invention provides novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPase's) such as PTP1B, CD45, SHP-1, SHP-2, PTPα, LAR and HePTP or the like. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, immune dysfunctions including autoimmunity diseases with dysfunctions of the coagulation system, allergic diseases including asthma, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases.
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(2008/06/13)

Synthesis of amino acid derivatives of 6-aminoquinoline antimalarial agents
Six new 6-aminoquinoline derivatives with amino acid in basic side chain were synthesized in order to modify their biological activities.
Jiranusornkul, Supat,Sirithunyalug, Busaban,Nemoto, Hideo,Takahata, Hiroki
p. 487 - 496
(2007/10/03)

Parallel synthesis and biological activity of a new class of high affinity and selective δ-opioid ligand
A considerable number of research papers describing the synthesis and testing of the delta opioid receptor (DOR) ligands, SNC-80 and TAN-67, and analogues of these two compounds, have been published in recent years. However, there have been few reports of the discovery of completely new structural classes of selective DOR ligand. By optimising a hit compound identified by high throughput screening, a new series of tetrahydroisoquinoline sulphonamide-based delta opioid ligands was discovered. The main challenge in this series was to simultaneously improve both affinity and physicochemical properties, notably aqueous solubility. The most active ligand had an affinity (IC50) of 6 nM for the cloned human DOR, representing a 15-fold improvement relative to the original hit 1 (IC50 98 nM). Compounds from this new series show good selectivity for the DOR over μ and κ opioid receptors. However the most active and selective compounds had poor aqueous solubility. Improved aqueous solubility was obtained by replacing the phthalimide group in 1 by basic groups, allowing the synthesis of salt forms. A series of compounds with improved affinity and solubility relative to 1 was identified and these compounds showed activity in an in vivo model of antinociception, the formalin paw test. In the case of compound 19, this analgesic activity was shown to be mediated primarily via a DOR mechanism. The most active compound in vivo, 46, showed superior potency in this test compared to the reference DOR ligand, TAN-67 and similar potency to morphine (68% and 58% inhibition in Phases 1 and 2, respectively, at a dose of 10 mmol/kg i.v.).
Barn,Caulfield,Cottney,McGurk,Morphy,Rankovic,Roberts
p. 2609 - 2624
(2007/10/03)

Synthesis of pyrrolo[2,3-d]pyrimidines via cyclocondensation of β-alkoxy- and β-amino-α-bromoaldehydes
A series of β-alkoxy- and β-amino-α-bromoaldehydes was synthesized. The cyclocondensation of these intermediates with 2,4-diamino-6-hydroxypyrimidine yielded a series of pyrrolo[2,3-d]pyrimidines containing heteroatoms in the side chain. Choice of protecting group proved critical to the success of the bromination and cyclocondensation reactions. A number of oxygen and nitrogen protecting groups were examined and the results are described herein. (C) 2000 Elsevier Science Ltd.
Barnett,Grubb
p. 9741 - 9745
(2007/10/03)

Synthesis, CoMFA analysis, and receptor docking of 3,5-diacyl-2,4- dialkylpyridine derivatives as selective A3 adenosine receptor antagonists
3,5-Diacyl-2,4-dialkyl-6-phenylpyridine derivatives have been found to be selective antagonists at both human and rat A3 adenosine receptors (Li et al. J. Med. Chem. 1998, 41, 3186-3201). In the present study, ring- constrained, fluoro, hydroxy, and other derivatives in this series have been synthesized and tested for affinity at adenosine receptors in radioligand binding assays. K(i) values at recombinant human and rat A3 adenosine receptors were determined using [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)- 5'-N-methylcarbamoyladenosine). Selectivity for A3 adenosine receptors was determined vs radioligand binding at rat brain A1 and A(2A) receptors, and structure-activity relationships at various positions of the pyridine ring (the 3- and 5-acyl substituents and the 2- and 4-alkyl substituents) were probed. At the 5-position inclusion of a β-fluoroethyl (7) or a γ- fluoropropyl ester (26) was favorable for human A3 receptor affinity, resulting in K(i) values of 4.2 and 9.7 nM, respectively, while the pentafluoropropyl analogue was clearly less potent at human A3 receptors. At the 2-, 3-, and 4-positions, fluoro or hydroxy substitution failed to enhance potency and selectivity at human A3 receptors. Several analogues were nearly equipotent at rat and human A3 receptors. To further define the pharmacophore conformationally, a lactam, a lactone, and thiolactones were tested in adenosine receptor binding. The most potent analogue in this group was compound 34, in which a thiolactone was formed between 3- and 4-positions and which had a K(i) value of 248 nM at human A3 receptors. Using affinity data and a general pharmacophore model for A3 adenosine receptor antagonists recently proposed, we applied comparative molecular field analysis (CoMFA) to obtain a three dimensional quantitative structure-activity relationship for pyridine derivatives, having good predictability (r2(pred) = 0.873) for compounds in the test set. A rhodopsin-based model of the human As receptor was built, and the pyridine reference ligand 2,3,4,5-tetraethyl-6-phenyl- pyridine-3-thiocarboxylate-5-carboxylate (MRS 1476) was docked in the putative ligand binding site. Interactions between receptor transmembrane domains and the steric and the electrostatic contour plots obtained from the CoMFA analysis were analyzed.
Li, An-Hu,Moro, Stefano,Forsyth, Nancy,Melman, Neli,Ji, Xiao-Duo,Jacobson, Kenneth A.
p. 706 - 721
(2007/10/03)

Integrin receptor antagonists
This invention relates to novel heterocycle compounds including but not limited to 3-?3-?3-(imidazolin-2-yl amino)propyloxy!isoxazol-5-ylcarbonylamino!-2-(benzyloxycarbonylamino)-propionic acid, which are useful as antagonists of the αv β3 and related integrin receptors, to pharmaceutical compositions containing such compounds, processes for preparing such compounds, and to methods of using these compounds, alone or in combination with other therapeutic agents, for the inhibition of cell adhesion and the treatment of angiogenic disorders, inflammation, bone degradation, tumors, metastases, thrombosis, and other cell aggregation-related conditions.
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(2008/06/13)

Highly enantioselective hydroformylation of olefins catalyzed by rhodium(I) complexes of new chiral phosphine-phosphite ligands
A new chiral phosphine-phosphite ligand, (R)-2-(diphenylphosphino)- 1,1'-binaphthalen-2'-yl (S)-1,1'-binaphthalene-2,2'-diyl phosphite [(R,S)- BINAPHOS, (R,S)-2a], was synthesized. Its Rh(I) complex was prepared, and its structure has been characterized by 1H and 31P NMR spectroscopy. Using Rh(I) complexes of (R,S)-2a and its enantiomer, highly enantioselective hydroformylation of styrene has been performed (94% ee, iso/normal = 88/12). The catalyst system was also effective for a variety of other olefins. Some other phosphine-phosphite ligands bearing 1,1'-binaphthyl and biphenyl backbones, such as (S)-3,3'-dichloro-6-(diphenylphosphino)-2,2',4,4'- tetramethylbiphenyl-6'-yl (R)-1,1'-binaphthalene-2,2'-diyl phosphite [(S,R)- BIPHEMPHOS. (S,R)-5a], (R,R)-2a, (R,S)-2b, (R)-2c, and (R)-5b, were tested for asymmetric hydroformylation. The results indicate that the sense of enantioface selection for the prochiral olefins is mainly determined by the absolute configuration of the phosphine site, for example, the (R)-2- (diphenylphosphino)-1,1'-binaphthalen-2'-yl group in (R,S)-2a. The relative configurations of the two biaryl groups in the phosphine-phosphites play crucial roles in the degree of the enantioselectivities, that is, the (R,S)- isomer generally gives products in high ee's and the (R*,R*)-isomer does in low ee's. Treatment of Rh(acac)[(R,S)-2a] with a 1:1 mixture of carbon monoxide and hydrogen gave a hydridorhodium complex. RhH-(CO)2[(R,S)-2a], as a single species. Trigonal bipyramidal structure is suggested for this complex, in which the hydride and the phosphite moiety are located at the apical positions and the phosphine and the two carbonyls occupy the equatorial positions. The interchange of the phosphine and the phosphite sites with each other through rapid pseudorotations has not been observed in RhH(CO)2[(R,S)-2a]. The structural deviations of the monohydride complexes from an ideal trigonal bipyramid seem to be larger in (R*,R*)-isomers than in the corresponding (R*,S*)-isomers. The existence of only one active species involved in the Rh(1)-(R,S)-2a-catalyzed hydroformylation has been manifested by the plot of ln([R]/[S]) of the hydroformylation product vs the reciprocals of the reaction temperatures. The higher thermodynamic stability of Rh(acac)[(R,S)-2a] than its diastereomer Rh(acac)[(R,R)-2a] is demonstrated in relation to the restricted configuration of (R)-2c to (R,S)- 2c in its complex formation with Rh(1).
Nozaki, Kyoko,Sakai, Nozomu,Nanno, Tetsuo,Higashijima, Takanori,Mano, Satoshi,Horiuchi, Toshihide,Takaya, Hidemasa
p. 4413 - 4423
(2007/10/03)

Synthesis of L-ornithines stereospecifically deuterated at C-3
(2S, 3S)-[2,3-2H2]-Ornithine and (2S, 3R)-[3-2H1]-ornithine were prepared with high stereoselectivity via asymmetric reduction catalysed by {bicyclo[2.2.1]hepta-2,5-diene}{(R)-1,2-bis(diphenylphosphino)propa ne}rhodium (I) trifluoromethanesulphonate [(R)-Rh-Prophos].
Baldwin,Merritt,Schofield
p. 3919 - 3920
(2007/10/02)