- Catalyst-Free Electrophilic Ring Expansion of N-Unprotected Aziridines with α-Oxoketenes to Efficient Access 2-Alkylidene-1,3-Oxazolidines
-
2-(2-Oxoalkylidene)-1,3-oxazolidine derivatives were synthesized in good to excellent yields regiospecifically through the catalyst-free electrophilic ring expansion of N-unprotected aziridines and the ketene C=O double bond of α-oxoketenes, in situ generated from the microwave-assisted Wolff rearrangement of 2-diazo-1,3-diketones. The ring expansion predominantly underwent an SN1 process and the hydrogen bond decides the (E)-configuration of products. (Figure presented.).
- Chen, Xingpeng,Huang, Zhengshuo,Xu, Jiaxi
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p. 3098 - 3108
(2021/05/10)
-
- Application of an Electrochemical Microflow Reactor for Cyanosilylation: Machine Learning-Assisted Exploration of Suitable Reaction Conditions for Semi-Large-Scale Synthesis
-
Cyanosilylation of carbonyl compounds provides protected cyanohydrins, which can be converted into many kinds of compounds such as amino alcohols, amides, esters, and carboxylic acids. In particular, the use of trimethylsilyl cyanide as the sole carbon source can avoid the need for more toxic inorganic cyanides. In this paper, we describe an electrochemically initiated cyanosilylation of carbonyl compounds and its application to a microflow reactor. Furthermore, to identify suitable reaction conditions, which reflect considerations beyond simply a high yield, we demonstrate machine learning-assisted optimization. Machine learning can be used to adjust the current and flow rate at the same time and identify the conditions needed to achieve the best productivity.
- Sato, Eisuke,Fujii, Mayu,Tanaka, Hiroki,Mitsudo, Koichi,Kondo, Masaru,Takizawa, Shinobu,Sasai, Hiroaki,Washio, Takeshi,Ishikawa, Kazunori,Suga, Seiji
-
p. 16035 - 16044
(2021/09/02)
-
- The hydrogenation of mandelonitrile over a Pd/C catalyst: Towards a mechanistic understanding
-
A carbon supported Pd catalyst is used in the liquid phase hydrogenation of the aromatic cyanohydrin mandelonitrile (C6H5CH(OH)CH2CN) to afford the primary amine phenethylamine (C6H5CH2CH2NH2). Employing a batch reactor, the desired primary amine is produced in 87% selectivity at reaction completion. Detection of the by-product 2-amino-1-phenylethanol (C6H5CH(OH)CH2NH2) accounts for the remaining 13% and closes the mass balance. The reaction mechanism is investigated, with a role for both hydrogenation and hydrogenolysis processes established.
- McAllister, Mairi I.,Boulho, Cédric,McMillan, Liam,Gilpin, Lauren F.,Brennan, Colin,Lennon, David
-
p. 26116 - 26125
(2019/09/09)
-
- Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein
-
Chiral 1,2-amino alcohols are widely represented in biologically active compounds from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcohols, the direct aminohydroxylation of alkenes to unprotected, enantioenriched amino alcohols remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable cytochrome c that directly transforms alkenes to amino alcohols with high enantioselectivity (up to 2500 TTN and 90 % ee) under anaerobic conditions with O-pivaloylhydroxylamine as an aminating reagent. The reaction is proposed to proceed via a reactive iron-nitrogen species generated in the enzyme active site, enabling tuning of the catalyst's activity and selectivity by protein engineering.
- Cho, Inha,Prier, Christopher K.,Jia, Zhi-Jun,Zhang, Ruijie K.,G?rbe, Tamás,Arnold, Frances H.
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p. 3138 - 3142
(2019/02/01)
-
- Nitration-Peroxidation of Alkenes: A Selective Approach to β-Peroxyl Nitroalkanes
-
Nitration-peroxidation of alkenes for the synthesis of β-peroxyl nitroalkanes has been developed by using tert-butyl nitrite and tert-butyl hydroperoxide. The method presents a new and selective difunctionalization of alkenes to introduce a nitro group and a peroxyl group across the double bonds of alkenes under mild conditions. A radical reaction pathway is proposed by experimental and theoretical studies.
- Chen, Yuanjin,Ma, Yangyang,Li, Liangkui,Jiang, Hao,Li, Zhiping
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p. 1480 - 1483
(2019/02/26)
-
- Selective oxidation of thioanisole with hydrogen peroxide using copper complexes encapsulated in zeolite: Formation of a thermally stable and reactive copper hydroperoxo species
-
[Cu(terpy)]2+ complexes encapsulated into Na-Y zeolite ([Cu(terpy)]2+@Y) were prepared, and their catalytic activities for the oxidation of sulfides using hydrogen peroxide were investigated. Several spectroscopic results, as well as elemental analysis, demonstrated the formation of [Cu(terpy)]2+ complexes in supercages of Y-zeolite. [Cu(terpy)]2+@Y exhibited high selectivity for the oxidation of thioanisole into methylphenylsulfoxide when H2O2 was used. The kinetic study of this oxidation at the catalyst [Cu(terpy)]2+@Y suggests that the reaction of [Cu(terpy)]2+ species with H2O2 is the rate-determining step. The oxidation of thioanisole, benzene, and 2-phenylethylamine using [[Cu(terpy)]2+@Y]?, which was prepared from the reaction between [Cu(terpy)]2+@Y and H2O2, quantitatively proceeded to methylphenylsulfoxide, phenol, and 2-amino-1-phenylethanol, respectively. The reaction of [Cu(terpy)]2+@Y and H2O2 was found to yield thermally stable but active CuII-OOH species in [Cu(terpy)]2+@Y.
- Yamaguchi, Syuhei,Suzuki, Akinori,Togawa, Makoto,Nishibori, Maiko,Yahiro, Hidenori
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p. 2645 - 2650
(2018/04/14)
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- In silico prioritization, synthesis and in vitro evaluation of tembamide analogs for anti-HIV activity
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Background: High attrition rate in late drug discovery and development stages leads to financial loss to industries and Governments. Despite the global prevalence of HIV infection and lack of promising treatment for AIDS patients, there are only a few drugs approved for the management of infected patients. There is an urgent need to discover newer anti-HIV drugs with novel mechanism of action and with efforts to reduce attrition rate in early drug discovery stages. Objective: Prioritization of reported potential anti-HIV-1 leads according to their quantitative estimation of druglikeness (QED), carcinogenicity, mutagenicity, absorption, metabolism and toxic properties. Synthesis of analogs of the best lead and evaluation of their anti-HIV-1 activity is shown. Methods: In silico anti-HIV lead prioritization was performed on a set of known anti-HIV natural products in order to obtain a lead with better druglikeness and ADMET properties. Prioritized lead tembamide and its four analogs were synthesized and their anti-HIV-1 activity was evaluated. Results: Tembamide was found to be a lead with better QED, absorption and metabolism properties and with no carcinogenicity, mutagenicity and toxic potential. (+)-Tembamide is previously reported to show potent anti-HIV-1 activity against laboratory adapted strains HIV-1IIIB (X4, subtype B) and HIV-1Ada5 (R5, subtype B) in H9 cell line. It was observed during this study that synthesized tembamide and its four analogs were weakly active against primary isolates HIV-1UG070 (X4, subtype D) and HIV-1VB59 (R5, subtype C) in TZM-bl cell line. Conclusion: The results showed that there is scope for the improvement of activity of tembamide analogs to discover a potent anti-HIV compound.
- Gupta, Shiv,Kumar, Sanjay,Jariwala, Nisha,Bhadane, Deepali,Bhutani, Kamlesh Kumar,Kulkarni, Smita,Singh, Inder Pal
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p. 1455 - 1464
(2017/12/28)
-
- Remote C(sp3)-H Oxygenation of Protonated Aliphatic Amines with Potassium Persulfate
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This letter describes the development of a method for selective remote C(sp3)-H oxygenation of protonated aliphatic amines using aqueous potassium persulfate. Protonation serves to deactivate the proximal C(sp3)-H bonds of the amine substrates and also renders the amines soluble in the aqueous medium. These reactions proceed under relatively mild conditions (within 2 h at 80 °C with amine as limiting reagent) and do not require a transition metal catalyst. This method is applicable to a variety of types of C(sp3)-H bonds, including 3°, 2°, and benzylic C-H sites in primary, secondary, and tertiary amine substrates.
- Lee, Melissa,Sanford, Melanie S.
-
supporting information
p. 572 - 575
(2017/02/10)
-
- Direct catalytic synthesis of unprotected 2-amino-1-phenylethanols from alkenes by using iron(II) phthalocyanine
-
Aryl-substituted amino alcohols are privileged scaffolds in medicinal chemistry and natural products. Herein, we report that an exceptionally simple and inexpensive FeII complex efficiently catalyzes the direct transformation of simple alkenes into unprotected amino alcohols in good yield and perfect regioselectivity. This new catalytic method was applied in the expedient synthesis of bioactive molecules and could be extended to aminoetherification.
- Legnani, Luca,Morandi, Bill
-
supporting information
p. 2248 - 2251
(2016/02/18)
-
- Lewis acid mediated intramolecular C-O bond formation of alkanol-epoxide leading to substituted morpholine and 1,4-oxazepane derivatives: Total synthesis of (±)-Viloxazine
-
Substituted morpholines have been efficiently synthesised in good yields from nitrogen tethered alkanol-epoxide mediated by boron trifluoride etherate. The methodology has been used for the total synthesis of (±)-viloxazine.
- Ghosh, Priya,Deka, Manash J.,Saikia, Anil K.
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p. 690 - 698
(2016/01/15)
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- Aminohydroxylation of olefins with iminopyridinium ylides by dual Ir photocatalysis and Sc(OTf)3catalysis
-
We have developed a new strategy for catalytic aminohydroxylation of olefins with an N-protected iminopyridinium ylide as the amine source. Iminopyridinium ylides N-protected with TFAc (trifluoroacetyl), Boc (tert-butoxycarbonyl), Troc (2,2,2-trichloroethoxycarbonyl), and Alloc (allyloxycarbonyl) groups serve as N-centered radical precursors when combined with fac-[Ir(ppy)3] photocatalysis and Sc(OTf)3catalysis. The dual Ir photoredox/Sc(OTf)3catalysis proves to be effective for aminohydroxylation of olefins under mild reaction conditions to provide 2-aminoalcohol derivatives bearing a primary amino group.
- Miyazawa, Kazuki,Koike, Takashi,Akita, Munetaka
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p. 7813 - 7820
(2016/11/16)
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- Efficient chemoselective hydrogenation of organic azides catalyzed by palladium nanoparticles with alkyne-derived homogeneous supports
-
Catalytic chemoselective hydrogenation of organic azides using palladium nanoparticles stabilized by alkyne derivatives was studied. A broad range of aromatic and aliphatic azides were smoothly reduced to the corresponding amines in excellent yields with a quite small amount of the catalyst. Hydrogenation of 3-phenylpropylazide gave 3-phenylpropylamine almost quantitatively with a substrate-to-palladium molar ratio (S/Pd) of 12,900 under 8?atm of H2. The reaction under 1?atm of H2also proceeded smoothly with an S/Pd of 1000. Several reduction-sensitive functional groups, such as carbonyl, halide, benzylic OH, and aliphatic nitro were well tolerated under the reaction conditions.
- Arai, Noriyoshi,Onodera, Nozomi,Ohkuma, Takeshi
-
supporting information
p. 4183 - 4186
(2016/08/24)
-
- Kinetic resolution of racemic amino alcohols through intermolecular acetalization catalyzed by a chiral Bronsted acid
-
The kinetic resolution of racemic secondary alcohols is a fundamental method for obtaining enantiomerically enriched alcohols. Compared to esterification, which is a well-established method for this purpose, kinetic resolution through enantioselective intermolecular acetalization has not been reported to date despite the fact that the formation of acetals is widely adopted to protect hydroxy groups. By taking advantage of the thermodynamics of acetalization by the addition of alcohols to enol ethers, a highly efficient kinetic resolution of racemic amino alcohols was achieved for the first time and in a practical manner using a chiral phosphoric acid catalyst.
- Yamanaka, Takuto,Kondoh, Azusa,Terada, Masahiro
-
supporting information
p. 1048 - 1051
(2015/02/19)
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- 1-Aryl-2-((6-aryl)pyrimidin-4-yl)amino)ethanols as competitive inhibitors of fatty acid amide hydrolase
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A series of 1-aryl-2-(((6-aryl)pyrimidin-4-yl)amino)ethanols have been found to be competitive inhibitors of fatty acid amide hydrolase (FAAH). One member of this class, JNJ-40413269, was found to have excellent pharmacokinetic properties, demonstrated robust central target engagement, and was efficacious in a rat model of neuropathic pain.
- Keith, John M.,Hawryluk, Natalie,Apodaca, Richard L.,Chambers, Allison,Pierce, Joan M.,Seierstad, Mark,Palmer, James A.,Webb, Michael,Karbarz, Mark J.,Scott, Brian P.,Wilson, Sandy J.,Luo, Lin,Wennerholm, Michelle L.,Chang, Leon,Rizzolio, Michele,Chaplan, Sandra R.,Breitenbucher, J. Guy
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p. 1280 - 1284
(2014/03/21)
-
- Purification and characterization of a novel carbonyl reductase involved in oxidoreduction of aromatic β-amino ketones/alcohols
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Aromatic β-amino ketones/alcohols such as adrenalone play an important role in some stereoselective synthesis of pharmaceuticals. Unfortunately, the transformation of aromatic β-amino ketones to their chiral alcohols has been carried out chemically as no corresponding biocatalyst has been available. Here, a novel carbonyl reductase responsible for the reduction of adrenalone to (R)-(-)-epinephrine was identified and characterized from Kocuria rhizophila. This enzyme was purified to homogeneity by ammonium sulfate precipitation followed by ion-exchange column chromatography, hydrophobic chromatography and gel chromatography. The purified enzyme yielded pure (R)-enantiomer product with high activity and utilized NADH as the cofactor. The enzyme had special significance by showing selectivity for many aromatic β-amino ketones/alcohols such as 2-amino-acetophenone, 2-amino-4′- hydroxyacetophenone, isoproterenol and ephedrine. The maximum reaction rate (Vmax) and apparent Michaelis-Menten constant (Km) for adrenalone and NADH were 14.62 μmol/(min mg) protein and 0.189 mM, 11.66 μmol/(min mg) protein and 0.204 mM respectively. These properties ensure the enzyme a promising future for industrial application as a replacement of chemical synthesis of aromatic β-amino chiral alcohols.
- He, Shengbin,Wang, Zhenshou,Zou, Yang,Chen, Shaofang,Xu, Xiaoping
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p. 1107 - 1112
(2014/06/10)
-
- Efficient preparation of biologically important 1,2-amino alcohols
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An efficient three-step methodology developed for the preparation of 1,2-amino alcohols. In the first step a rapid coupling between bromoketones and potassium phthalimide in ionic liquid produced-phthalimido ketones in quantitative yields, which is followed by a facile reduction using NaCNBH 3 in acetic acid to give corresponding phthalimido alcohols and finally effecting hydrazinolysis in water at 60C to yield biologically important 1,2-amino alcohols.
- Gupta, Pankaj,Rouf, Abdul,Shah, Bhahwal A.,Mukherjee, Debaraj,Taneja, Subhash C.
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p. 505 - 519
(2013/01/15)
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- One-pot combination of enzyme and Pd nanoparticle catalysis for the synthesis of enantiomerically pure 1,2-amino alcohols
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One-pot combinations of sequential catalytic reactions can offer practical and ecological advantages over classical multi-step synthesis schemes. In this context, the integration of enzymatic and chemo-catalytic transformations holds particular potential for efficient and selective reaction sequences that would not be possible using either method alone. Here, we report the one-pot combination of alcohol dehydrogenase-catalysed asymmetric reduction of 2-azido ketones and Pd nanoparticle-catalysed hydrogenation of the resulting azido alcohols, which gives access to both enantiomers of aromatic 1,2-amino alcohols in high yields and excellent optical purity (ee >99%). Furthermore, we demonstrate the incorporation of an upstream azidolysis and a downstream acylation step into the one-pot system, thus establishing a highly integrated synthesis of the antiviral natural product (S)-tembamide in 73% yield (ee >99%) over 4 steps. Avoiding the purification and isolation of intermediates in this synthetic sequence leads to an unprecedentedly low ecological footprint, as quantified by the E-factor and solvent demand.
- Schrittwieser, Joerg H.,Coccia, Francesca,Kara, Selin,Grischek, Barbara,Kroutil, Wolfgang,D'Alessandro, Nicola,Hollmann, Frank
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p. 3318 - 3331
(2013/12/04)
-
- Regio-selective synthesis of 1,2-aminoalcohols from epoxides and chlorohydrins
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A simple and efficient procedure for the regio-selective synthesis of 1,2-aminoalcohols from terminal epoxides and chlorohydrins by using NaHMDS as the source of amine is reported. The wider scope and utility of this method is demonstrated.
- Murugan, Andiappan,Kadambar, Vasantha Krishna,Bachu, Sreekanth,Rajashekher Reddy,Torlikonda, Venkatarao,Manjunatha, Sulur G.,Ramasubramanian, Sridharan,Nambiar, Sudhir,Howell, Gareth P.,Withnall, Jane
-
supporting information
p. 5739 - 5741
(2012/11/06)
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- Novel amide- and sulfonamide-based aromatic ethanolamines: Effects of various substituents on the inhibition of acid and neutral ceramidases
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In the present study we describe the design and synthesis of a series of amide- and sulfonamide-based compounds as inhibitor of recombinant acid and neutral ceramidases. Inhibition of ceramidases has been shown to induce apoptosis and to increase the efficacy of conventional chemotherapy in several cancer models. B-13, lead in vitro inhibitor of acid ceramidase has been recently shown to be virtually inactive towards lysosomal acid ceramidase in living cells at lower concentrations and for a shorter time of treatment, suggesting the development of more potent inhibitors. In this study, a detailed SAR investigation has been performed to understand the effect of different substituents on the phenyl ring of amide- and sulfonamide-based compounds that partially resemble the structure of well-known inhibitors such as B-13, D-e-MAPP as well as NOE. Our results suggest that the electronic effects of the substituents on phenyl ring in B-13 and D-e-MAPP analogues have negligible effects either in enhancing the inhibition potencies or for selectivity towards aCDase over nCDase. However, the hydrophobicity and the steric effects of longer alkyl chains (n-Pr, n-Bu or t-Bu groups) at the phenyl ring were found to be important for an enhanced selectivity towards aCDase over nCDase.
- Bhabak, Krishna P.,Arenz, Christoph
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p. 6162 - 6170
(2012/11/06)
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- A novel reaction of α-carbonyl oxime and amido alcohol: Synthesis, characterization, crystal structure, and thermal studies of an amido alcohol, a new oximino alcohol ligand, and its metal complexes
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In this study, a novel reaction was observed between isonitrosoacetophenone and 1-phenylethanol amine. Acetophenone was used as a starting material to synthesize isonitrosoacetophenone by reaction of acetophenone with n-butyl nitrite in the presence of sodium ethoxide and to synthesize 1-phenylethanol amine by reduction of isonitrosoacetophenone with LiAlH4 in diethyl ether. When the isonitrosoacetophenone reacted with 1-phenylethanol amine, (3E)-3-aza-5-(hydroxyimino)-1,4-diphenylpent-3-en-1-ol monohydrate, a new oximino alcohol ligand and amido alcohol were obtained as associated product interestingly. Four complexes were prepared by treatment of oximino alcohol with metal salts such as CuII, NiII, ZnII, and CoII. Amido alcohol was characterized by single-crystal X-ray diffraction, and all complexes were characterized by using spectroscopic techniques and thermogravimetric analysis (TGA). Copyright Taylor &Francis Group, LLC.
- Kaya, Yunus,Irez, Gazi,Mutlu, Hasene,Buyukgungor, Orhan
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experimental part
p. 754 - 762
(2011/10/05)
-
- Reduction of alkyl and aryl azides with sodium thiophosphate in aqueous solutions
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A simple aqueous method for the conversion of alkyl and aryl azides into the corresponding amines using trisodium thiophosphate is presented. Thiophosphate is converted into phosphate during these formal reduction processes.
- Norcliffe, Jennifer L.,Conway, Louis P.,Hodgson, David R.W.
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supporting information; experimental part
p. 2730 - 2732
(2011/06/19)
-
- Synthesis of N-substituted Clausenamide analogues
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A practical synthesis of N-substituted Clausenamide analogues, including (-) and (+) CM1, Piracetam analogue 1 and Nefiracetam analogue 2, have been developed.
- Li, Xingzhou,Zhu, Chuangjiang,Li, Changhui,Wu, Kemei,Huang, Daofei,Huang, Liang
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experimental part
p. 5531 - 5538
(2010/12/25)
-
- Synthesis and cytotoxicity of 1-phenylethanolamine carboxamide derivatives: Effects on the cell cycle
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Seven novel analogues of 1-phenylethanolamine carboxamide derivatives, 3a-3g, related to carboxamides isolated from Isodon excisus were synthesized and evaluated for their cytotoxic and apoptosis-induction properties against murine B16 and leukemia L1210 cell lines. Compounds containing no substitution at the 4′-position (3a-3d) or containing a 4′-amino (3e-3g) group were investigated. Generally, the amino-containing compounds were slightly more active than their unsubstituted congeners. Also, the indole-containing compounds 3c and 3f gave the strongest cytotoxic activity (IC50 = 25-87 μM) against the growth of L1210 and B16 cancer cells. Compound 3f was subjected to flow cytometry studies and it was found to induce L1210 cells grown in culture to undergo apoptosis.
- Babu, Balaji,Forrest, Lori,Weisbruch, Paul,Chavda, Sameer,Pati, Hari,Lee, Moses
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experimental part
p. 1141 - 1152
(2011/10/03)
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- Asymmetric oxidations of electron-poor alkenes promoted by the β-amino alcohol/TBHP system
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The asymmetric oxyfunctionalization of alkenes is a fundamental process in synthetic organic chemistry. In this contribution, we review our findings on the enantioselective organocatalyzed oxidation of electron-poor alkenes. Readily or commercially available β-amino alcohols displayed catalytic activity in the asymmetric epoxidation of α,β-enones and β-peroxidation of nitroalkenes with tert-butyl hydroperoxide (TBHP) as the oxidant. The corresponding epoxides and peroxides were isolated in good to high yield and enantioselectivity. Georg Thieme Verlag Stuttgart.
- Russo, Alessio,Lattanzi, Alessandra
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scheme or table
p. 1551 - 1556
(2009/12/06)
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- Design and synthesis of a functionally selective D3 agonist and its in vivo delivery via the intranasal route
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This paper reports the synthesis and biological activity of a novel series of aryl-morpholine dopamine receptor agonists. Several compounds show high levels of functional selectivity for the D3 over the D2 dopamine receptor. Compound 26 has >1000-fold functional selectivity and has been successfully progressed in vivo using an intranasal delivery route.
- Blagg, Julian,Allerton, Charlotte M.N.,Batchelor, David V.J.,Baxter, Andrew D.,Burring, Denise J.,Carr, Christopher L.,Cook, Andrew S.,Nichols, Carly L.,Phipps, Joanne,Sanderson, Vivienne G.,Verrier, Hugh,Wong, Stephen
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p. 6691 - 6696
(2008/03/14)
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- Synthesis of aromatic 1,2-amino alcohols utilizing a bienzymatic dynamic kinetic asymmetric transformation
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The applicability of the recent published bienzymatic protocol for the synthesis of (R)-2-amino-1-phenylethanol was tested using L-threonine aldolase from Pseudomonas putida and L-tyrosine decarboxylase from either Enterococcus faecalis (Efa) or two genes from Enterococcus faecium (Efil, Efi2). In all 21 benzaldehyde derivatives were applied for an initial TLC screening. On a small scale, octopamine and noradrenaline were obtained as (S)-enantiomers using Efil. Three protocols were upscaled yielding enantioenriched (S)-octopamine (yield 99%, ee 81%), (R)-2-amino-1-phenylethanol (yield 61%, ee 62%) and (S)-noradrenaline (yield 76%, ee 79%).
- Steinreiber, Johannes,Schuermann, Martin,Van Assema, Friso,Wolberg, Michael,Fesko, Kateryna,Reisinger, Christoph,Mink, Daniel,Griengl, Herfried
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p. 1379 - 1386
(2008/04/03)
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- Novel 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin-like growth factor I (IGF-1R) kinase
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A novel class of 1H-(benzimidazol-2-yl)-1H-pyridin-2-one inhibitors of insulin-like growth factor I (IGF-1R) kinase is described. This report discusses the SAR of 4-(2-hydroxy-2-phenylethylamino)-substituted pyridones with improved IGF-1R potency.
- Wittman, Mark D.,Balasubramanian, Balu,Stoffan, Karen,Velaparthi, Upender,Liu, Pieying,Krishnanathan, Subramaniam,Carboni, Joan,Li, Aixin,Greer, Ann,Attar, Ricardo,Gottardis, Marco,Chang, Chiehying,Jacobson, Bruce,Sun, Yax,Hansel, Steven,Zoeckler, Mary,Vyas, Dolatrai M.
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p. 974 - 977
(2007/10/03)
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- Asymmetric hydrogenation of α-primary and secondary amino ketones: Efficient asymmetric syntheses of (-)-arbutamine and (-)-denopamine
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Two ss-receptor agonists (-)-denopamine and (-)-arbutamine were prepared in good yields and enantioselectivities by asymmetric hydrogenation of unprotected amino ketones for the first time by using Rh catalysts bearing electron-donating phosphine ligands. A series of α-primary and secondary amino ketones were synthesized and hydrogenated to produce various 1,2-amino alcohols in good yields and with good enantioselectivies. This Rh electron-donating phosphine-catalyzed asymmetric hyderogenation repI resents one of the most promising and convenient approaches towards the asymmetric synthesis of chiral amino alcohols.
- Shang, Gao,Liu, Duan,Allen, Scott E.,Yang, Qin,Zhang, Xumu
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p. 7780 - 7784
(2008/04/03)
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- Effective procedure for selective ammonolysis of monosubstituted oxiranes: application to E7389 synthesis
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A highly effective procedure is reported to synthesize 1,2-aminoalcohols by regio- and chemo-selective ammonolysis of mono-substituted epoxides. Additive- and concentration-effects were studied, revealing that (1) methanesulfonic acid is most effective among the additives tested and (2) formation of bis-adducts is practically eliminated at [C] ≤ 40 mM. The optimum condition thus identified was successfully applied to the final step of the synthesis of potent anti-tumor compound E7389.
- Kaburagi, Yosuke,Kishi, Yoshito
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p. 8967 - 8971
(2008/03/18)
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- A General Route to the Synthesis of N-Protected 1-Substituted and 1,2-Disubstituted Taurines
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N-Benzyloxycarbonyl protected α-substituted and αβ- disubstituted taurines were synthesized from olefins and epoxides via N-benzyloxycarbonylamino alcohol thioacetates as key intermediates. They are important sulfur analogues of naturally occurring amino acids and building blocks for the synthesis of α-substituted and α,β- disubstituted β-sulfonopeptides.
- Xu, Jiaxi,Xu, Shu
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p. 276 - 282
(2007/10/03)
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- Pharmaceutically active pyrrolidine derivatives
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The present invention is related to pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of premature labor, premature birth and dysmenorrhea. In particular, the present invention is related to pyrrolidine derivatives displaying a substantial modulatory, notably an antagonist activity of the oxytocin receptor. More preferably, said compounds are useful in the treatment and/or prevention of disease states mediated by oxytocin, including premature labor, premature birth and dysmenorrhea. The present invention is furthermore related to novel pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of CR6R7, NOR6, NNR6R7; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO22—, —SO2NH—, —CH2—,B is either a group —(C═O)—NR8R9 or represents a heterocyclic residue having the formula (a) wherein Q is NR10, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.
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- SUBSTITUTED QUINAZOLINE DERIVATIVES AND THEIR USE AS INHIBITORS
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The use of a compound of formula (I) 1 or a salt, ester or amide thereof; where X is O, or S, S(O) or S(O)2, or NR6 where R6 is hydrogen or C1-6 alkyl,; R5 is an optionally substituted 5-membered heteroaromatic ring, R1, R2 ,R3, R4 are independently selected from various specified moieties, in the preparation of a medicament for use in the inhibition of aurora 2 kinase. Certain compounds are novel and these, together with pharmaceutical compositions containing them are also described and claimed
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- Pharmaceutically active pyrrolidine derivatives as bax inhibitors
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The present invention is related to new substituted pyrrolidine derivatives of formula (I). Said compounds are preferably for use as pharmaceutically active compounds. Specifically, pyrrolidine derivatives of formula (I) are useful in the treatment and/or prevention of neurodegenerative disorders, diseases associated with polygultamine tracts, epilepsy, ischemia, infertility, cardiovascular disorders renal hypoxia, hepatitis and AIDS. Said pyrrolidine derivatives display a modulatory and most notably a down-regulating-up to an inhibitory-activity with respect to the cellular death agonist Bax and/or the activation pathways leading to Bax and allows therefore to block the release of cytochrome (c). The present invention is furthermore related to novel pharmaceutically activity substituted pyrrolidine derivatives as well as to methods of their preparation, wherein X is selected from the group consisting of O, S, CRR, NOR, NNRR; A is selected from the group consisting of —(C═O)—, —(C═O)—O—, —C(═NH)—, —(C═O)—NH—, —(C═S)—NH, —SO2-, —SO2NH—; —CH2-; B is either a group —(C═O)—NRR or represents a heterocyclic residue having the formula (II) wherein Q is NR, O or S; n is an integer selected of 0, 1 or 2; Y, Z and E form together with the 2 carbons to which they are attached a 5-6 membered aryl or heteroaryl ring.
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- β-amino alcohol properfumes
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Amino-alcohol derivatives of fragrant, volatile aldehydes and ketones were synthesized in a one-pot procedure by sequential cyanohydrin formation with trimethylsilyl cyanide and reduction with lithium aluminium hydride, or by ammonolysis of epoxide precursors. The amino alcohols are nonvolatile, stable properfumes releasing fragrant carbonyls by oxidation with sodium periodate or sodium bismuthate. Examples include amino alcohol properfumes of citronellal, Lilial, lauryl aldehyde, menthone, benzaldehyde, and anisaldehyde.
- Yang, Yongzheng,Wahler, Denis,Reymond, Jean-Louis
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p. 2928 - 2936
(2007/10/03)
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- An efficient chemoselective production of amines from azides using AlCl3/NaBH4
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A practical reagent system AlCl3/NaBH4 is used for the preparation of amines from azides under mild reaction condition, in excellent yields.
- Raja Ram,Purushothama Chary,Salahuddin,Iyengar
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p. 935 - 937
(2007/10/03)
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- Convenient methods for the hydrolysis of oxazolidinones to vicinal aminoalcohols
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We have developed two convenient methods for hydrolysis of 2-oxazolidinones to the corresponding vicinal aminoalcohols. N-Substituted oxazolidinones can be readily hydrolyzed using Dowex 1×8-100 resin. N-Unsubstituted oxazolidinones cannot be hydrolyzed using Dowex resins but are effectively hydrolyzed using polymer supported ethylenediamine.
- Katz, Steven J,Bergmeier, Stephen C
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p. 557 - 559
(2007/10/03)
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- Processes for producing optically active 2-amino-1-phenylethanol derivatives
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An (R)-2-amino-1-phenylethanol derivative shown by the general formula (IIa) wherein R1 and R5 represent a hydrogen atom, etc.; R2, R3 and R4 independently represent a halogen atom, etc., or a salt thereof, can readily be produced (1) by permitting a Microorganism belonging to the genus Rhodosporidium, the genus Comamonas or the like to act on a mixture of corresponding (R)-form and (S)-form to asymmetrically utilize, or (2) by permitting a microorganism belonging to the genus Lodderomyces, the genus Pilimelia or the like to act on a corresponding aminoketone derivative to asymmetrically reduce. An (R,R)-1-phenyl-2-[(2-phenyl-1-alkylethyl) amino]ethanol derivative having a high optical purity can easily be obtained from the compound of the formula (IIa) or a salt thereof. Said derivative is useful as an intermediate for producing an anti-obesity agent and so on.
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- A novel, chemoselective and efficient production of amines from azides using ZrCl4/NaBH4
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A practical and cheaper reagent system ZrCl4/NaBH4 is used for the production of amines from azides is described.
- Purushothama Chary,Raja Ram,Salahuddin,Iyengar
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p. 3559 - 3563
(2007/10/03)
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- A novel and efficient production of amines from azides using LiCl/NaBH4
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A practical and efficient reagent system LiCl/NaBH4 is used for the production of amines from azides is described.
- Raja Ram,Purushothama Chary,Iyengar
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p. 4495 - 4500
(2007/10/03)
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- A new stable modified borohydride reagent. Efficient reduction of different functional groups with sulfurated barium borohydride [Ba(BH2S3)2] in dry THF
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Barium and strontium sulfurated borohydrides, Ba(BH2S3)2,Sr(BH2S3) 2 the two newly introduced modified borohydride agents, are prepared from NaBH2S3 by metathesis reaction with BaCl2 and SrCl2 in good yields. Ba(BH2S3)2 is more stable and more reactive than Sr(BH2S3)2. The reducing ability of Ba(BH2S3)2 for the reduction of aldehydes, ketones, α,β-unsaturated carbonyl compounds, azides, nitro compounds, and cleavage of epoxides in dry THF is described.
- Firouzabadi, Habib,Ghadami, Mahboobeh
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- Montmorillonite-K10 catalyzed addition of trimethylsilylcyanide (TMSCN) to aldehydes
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Addition of trimethylsilyl cyanide (TMSCN) to aldehydes was catalyzed by Montmorillonite-K10, with subsequent reduction to β-aminoalcohol.
- Somanathan,Rivero,Gama, Angeles,Ochoa,Aguirre
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p. 2043 - 2048
(2007/10/03)
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- Modified borohydride agents, bis(triphenylphosphine) (tetra-hydroborato)zinc complex [Zn(BH4)2(PPh3)2] and (triphenylphosphine) (tetrahydroborato)zinc complex [Zn(BH4)2(PPh3)]. New ligand metal borohydrides as stable, efficient, and versatile reducing agents
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Bis(triphenylphosphine)(tetrahydroborato)zinc and (triphenylphosphine)(tetrahydroborato) zinc complexes have been used for the efficient reductions of varieties of organic compounds in THF or under solvent free conditions. Selective reduction of aldehydes, ketones, α,β-unsaturated carbonyl compounds, and acyl chlorides to their corresponding alcohols and aryl, alkyl, aroyl, and sulfonyl azides to their corresponding amines and amides are described. Bis(triphenylphosphine)(tetrahydroboratro)zinc complex shows promising shelf stability and is much more stable than its mono triphenylphosphine analogue. The reducing ability of the two complexes is more or less the same.
- Firouzabadi, Habib,Adibi, Mina,Ghadami, Mahboobeh
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p. 191 - 220
(2007/10/03)
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- Modified borohydride agents; Efficient reduction of azides with (1,4- diazabicyclo[2.2.2]octane) (tetrahydroborato)zinc complex [Zn(BH4)2(dabco)] and methyltriphenylphosphonium tetrahydroborate [MePh3P+BH-4]
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(1,4-Diazabicyclo[2.2.2]octane)(tetrahydroborato)zinc complex and methyltriphenylphosphonium tetrahydroborate are stable modified borohydrides which are used for the efficient reduction of aryl, alkyl, and aroyl azides with excellent yields in THF or CH2Cl2 at room temperature or under reflux conditions.
- Firouzabadi,Adibi,Zeynizadeh
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p. 1257 - 1273
(2007/10/03)
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- Regio- and diastereoselective formation of 1,2-azidohydroperoxides by photooxygenation of alkenes in the presence of azide anions
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1,2-Azidohydroperoxides are accessible from alkenes when irradiated in the presence of azide anions, oxygen and an appropriate sensitizer. The results of substrate/sensitizer variations indicate a reaction initiated by electron transfer to give the sensitizer radical anion and azidyl radicals. The latter efficiently add to alkenes producing carbon radicals which are trapped by molecular oxygen.
- Griesbeck, Axel G.,Hundertmark, Thomas,Steinwascher, Joerg
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p. 8367 - 8370
(2007/10/03)
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- Synthesis of 2-Aryl-2,3-dihydro-oxazolopyrrolopyridin-5-one and 2-Aryl-2,3-dihydro-oxazolopyrrolopyridin-5-one
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A variety of 2-aryl-2,3-dihydro-oxazolopyrrolopyridin-5-one and 2-aryl-2,3-dihydro-oxazolopyrrolopyridin-5-one were prepared. The absolute configuration of the chiral centers were studied thoroughly from which the structural and stereoformulea of these compounds were deduced by using nmr and microanalysis technique.
- Makki, Mohamad S. I.,Samarkandy, Abdul-Rahim A.,Kabuli, Rida A.,Hewlins, M. J. E.
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- β-Amino alcohols from amino acids: Chelation control via Schiff bases
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Sequential addition of iBu2AlH and RLi or RMgX to Schiff base esters derived from amino acids provides a simple route to β-amino alcohols. The reaction procedes without racemization, and with high threo selectivity. Several representative sphingosines are synthesized.
- Polt,Peterson
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p. 4985 - 4986
(2007/10/02)
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- Synthetic Versatility of N(Silylmethyl)imines: Water-Induced Generation of N-Protonated Azomethine Ylides of Nonstabilized Type and Fluoride-Induced Generation of 2-Azallyl Anions
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N-(Silylmethyl)imines generate N-protonated azomethine ylides of nonstabilized type when treated with water in HMPA, which undergo stereospecific and regioselective cycloadditions with electron-poor olefins affording N-unsubstituted pyrrolidines.On the other hand, fluoride-induced desilylation of the imines leads to 2-azallyl anions which are found to be synthetic equivalents of aminomethyl anion in the Michael additions with electron-poor olefins and nucleophilic additions with carbonyl compounds.
- Tsuge, Otohiko,Kanemasa, Shuji,Hatada, Akira,Matsuda, Koyo
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p. 2537 - 2546
(2007/10/02)
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- Total Synthesis of (+/-) Resedine and (+/-)Resedinine Alkaloids from Reseda luteola
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Total synthesis of racemic alkaloids: resedine and resedinine is described.
- Mieczkowski, Jozef B.
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p. 109 - 113
(2007/10/02)
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- Nucleophilic Aminomethylation of Aldehydes with α-Amino Alkylsilanes
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Fluoride-induced desilylation of (α-phthalimido-, α-morpholino-, and α-acetamidobenzyl)silanes and a (phthalimidomethyl)silane generates the corresponding α-amino carbanions which add to a variety of aldehydes.The conversion of phthalimido group of the adducts into amino moiety leads to β-amino alcohols.This simple reaction sequence offers a new and general method of nucleophilic aminomethylation.
- Tsuge, Otohiko,Tanaka, Junji,Kanemasa, Shuji
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p. 1991 - 1999
(2007/10/02)
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- Determination des pKa et reaction d'ouverture acide de quelques alkyl-2 et aryl-2 aziridines
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Some 2-para substituted aryl aziridines (with pY = CH3O-, CH3-, H-, and Cl-) have been prepared.Their ring opening reaction in acidic medium has been studied and compared with those of two aliphatic aziridines : 2 methyl- and 2,2 dimethyl-aziridine.In aqueous solvent, the addition of HCl, HBr, and HI to the aromatic aziridines leads exclusively to the secondary halogen product, due to the nucleophilic attack on the benzylic carbon.The hydrolysis reaction competes with the addition reaction and is very important for the para methoxy 2-phenyl aziridine.In ethyl alcohol (anhydrous solvent), the hydrohalogenation reaction leads exclusively to halogeno amine with a secondary halogen.The solvolysis reaction, leading to amino-ether, is far less important than in water (excepted for the para methoxy 2-phenyl aziridine).In both solvents, the importance of the solvolysis depends on the HX concentration, as well as the nucleophilic strength of the halogen.The pKa values of these aziridines have been measured, as well as those of 2-phenyl 1-amino 2-ethanol.A linear plot is obtained for the pKa versus ?+p of Brown ; the slopes are respectively -2.8 and 0.Therefore the aromatic aziridines seem to have a behavior similar to that of anilines.
- Lamaty, Gerard,Sanchez, Jean-Yves,Sivade, Andre,Wylde, James
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p. 1261 - 1266
(2007/10/02)
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