- A modular, low footprint and scalable flow platform for the expedient α-aminohydroxylation of enolizable ketones
-
The unique reactivity profile of α-chloronitroso derivatives is expressed to its fullest potential through the development of an integrated, modular and scalable continuous flow process for the electrophilic α-aminohydroxylation of various enolizable ketones. Flow conditions contribute to mitigating the high reactivity and toxicity of α-chloronitroso derivatives and provide an efficient, versatile and safe protocol for the α-aminohydroxylation of ketones with a minimal footprint. Fundamental aspects of the α-aminohydroxylation process were computed by DFT and further supported the experimental observations, hence leading to the unprecedented α-chloronitroso-based α-aminohydroxylation of primary, secondary and tertiary substrates. Recycling of the carbon backbone of the α-chloronitroso derivatives provides a high atom economy for the preparation of value-added molecules. This work showcases α-chloronitroso derivatives as economic and efficient vehicles for transferring electrophilic synthons of hydroxylamine toward nucleophilic enolates. A representative range of precursors and analogs of pharmaceutical active ingredients, including WHO essentials and drugs in shortage (such as epinephrine and ketamine), are prepared within minutes according to a fully concatenated process. The process features sequential modules with distinct unit operations including chemical transformations and multiple in-line extractions. The process relies on an upstream chemical Generator that manages the preparation of α-chloronitroso derivatives and that feeds downstream a series of α-aminohydroxylation modules. The setup is amenable to the addition of libraries of compounds for feeding upstream the process of discovery in medicinal chemistry and is transposable to pilot scale. Several layers of in-line analytical procedures are featured to improve process control and safety.
- Kassin, Victor-Emmanuel H.,Morodo, Romain,Toupy, Thomas,Jacquemin, Isaline,Van Hecke, Kristof,Robiette, Rapha?l,Monbaliu, Jean-Christophe M.
-
supporting information
p. 2336 - 2351
(2021/04/07)
-
- Tetrasubstituted 1,3-Enynes by Gold-Catalyzed Direct C(sp2)-H Alkynylation of Acceptor-Substituted Enamines
-
A gold-catalyzed synthesis of tetrasubstituted 1,3-enynes from hypervalent iodine(III) reagents and activated alkenes is reported. This reaction involves an in situ formed alkynyl Au(III) species and a subsequent direct C(sp2)-H functionalization of alkenes, offering 26 enynes in 62-92% yield with excellent functional group tolerance.
- Han, Chunyu,Tian, Xianhai,Zhang, Huili,Rominger, Frank,Hashmi, A. Stephen K.
-
supporting information
p. 4764 - 4768
(2021/06/30)
-
- Dual Gold/Silver Catalysis: Indolizines from 2-Substituted Pyridine Derivatives via a Tandem C(sp3)–H Alkynylation/Iminoauration
-
A dual gold/silver-catalyzed cascade C(sp3)–H alkynylation/iminoauration of 2-substituted pyridines with hypervalent iodine(III) reagents for the synthesis of indolizines is described. This novel reaction involves the formation of an alkynyl Au(III) species, a dual gold/silver-catalyzed C(sp3)–H functionalization, and a subsequent iminoauration process. A number of indolizines bearing diverse functionalities were prepared in good to excellent yield. Furthermore, a gram-scale reaction was efficiently conducted.
- Han, Chunyu,Liu, Yaowen,Tian, Xianhai,Rominger, Frank,Hashmi, A. Stephen K.
-
supporting information
p. 9480 - 9484
(2021/12/17)
-
- Twofold Radical-Based Synthesis of N, C-Difunctionalized Bicyclo[1.1.1]pentanes
-
Bicyclo[1.1.1]pentylamines (BCPAs) are of growing importance to the pharmaceutical industry as sp3-rich bioisosteres of anilines and N-tert-butyl groups. Here we report a facile synthesis of 1,3-disubstituted BCPAs using a twofold radical functionalization strategy. Sulfonamidyl radicals, generated through fragmentation of α-iodoaziridines, undergo initial addition to [1.1.1]propellane to afford iodo-BCPAs; the newly formed C-I bond in these products is then functionalized via a silyl-mediated Giese reaction. This chemistry also translates smoothly to 1,3-disubstituted iodo-BCPs. A wide variety of radical acceptors and iodo-BCPAs are accommodated, providing straightforward access to an array of valuable aniline-like isosteres.
- Anderson, Edward A.,Mousseau, James. J.,Nugent, Jeremy,Owen, Benjamin,Pickford, Helena D.,Smith, Russell C.
-
supporting information
p. 9729 - 9736
(2021/07/19)
-
- Silicon-Free SuFEx Reactions of Sulfonimidoyl Fluorides: Scope, Enantioselectivity, and Mechanism
-
SuFEx reactions, in which an S?F moiety reacts with a silyl-protected phenol, have been developed as powerful click reactions. In the current paper we open up the potential of SuFEx reactions as enantioselective reactions, analyze the role of Si and outline the mechanism of this reaction. As a result, fast, high-yielding, “Si-free” and enantiospecific SuFEx reactions of sulfonimidoyl fluorides have been developed, and their mechanism shown, by both experimental and theoretical methods, to yield chiral products.
- Baggerman, Jacob,Jordaan, Daan,Liang, Dong-Dong,Streefkerk, Dieuwertje E.,Wagemakers, Jorden,Zuilhof, Han
-
supporting information
p. 7494 - 7500
(2020/03/23)
-
- Merging Natural Products: Muraymycin–Sansanmycin Hybrid Structures as Novel Scaffolds for Potential Antibacterial Agents
-
To overcome bacterial resistances, the need for novel antimicrobial agents is urgent. The class of so-called nucleoside antibiotics furnishes promising candidates for the development of new antibiotics, as these compounds block a clinically unexploited bacterial target: the integral membrane protein MraY, a key enzyme in cell wall (peptidoglycan) biosynthesis. Nucleoside antibiotics exhibit remarkable structural diversity besides their uridine-derived core motifs. Some sub-classes also show specific selectivities towards different Gram-positive and Gram-negative bacteria, which are poorly understood so far. Herein, the synthesis of a novel hybrid structure is reported, derived from the 5′-defunctionalized uridine core moiety of muraymycins and the peptide chain of sansanmycin B, as a new scaffold for the development of antimicrobial agents. The reported muraymycin–sansanmycin hybrid scaffold showed nanomolar activity against the bacterial target enzyme MraY, but displayed no significant antibacterial activity against S. aureus, E. coli, and P. aeruginosa.
- Niro, Giuliana,Weck, Stefanie C.,Ducho, Christian
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p. 16875 - 16887
(2020/11/30)
-
- Preparation and application of guaifenazulene aldole dicondensate (by machine translation)
-
The invention belongs to the field, and particularly relates to chemical preparation and application. When the problem group is subjected to chemical synthesis research on the skeleton by guaiguazulene and piperidine acid as raw materials, the derivative trans - 1, 2 - (1, 4 - diazulyl) ethene ene derivative of guaiabazulene is found. H1N1 Influenza virus testing, indicating that the compound is level, 25 mm in vitro antiviral activity superior to that of positive drug ribavirin. In vivo activity tests prove, the compound not only can inhibit the pneumonia symptoms, but also can reduce the titer, and the survival rate. , The survival rate, 5 mg/kg/day the lung virus titer . of virus-infected mice can be remarkably improved when stomach tube-like dosages are used for gastric lavage. In general, the activity of the compound is comparable, and the activity of the compound is comparable to that of oseltamivir. The utility model can be used for preparing antiviral drugs. The invention opens up a new way for deep research and development of new antiviral drugs, which is a new approach. (by machine translation)
- -
-
Paragraph 0021; 0022
(2019/08/02)
-
- KOtBu as a single electron donor? Revisiting the halogenation of alkanes with CBr4 and CCl4
-
The search for reactions where KOtBu and other tert-alkoxides might behave as single electron donors led us to explore their reactions with tetrahalomethanes, CX4, in the presence of adamantane. We recently reported the halogenation of adamantane under these conditions. These reactions appeared to mirror the analogous known reaction of NaOH with CBr4 under phase-transfer conditions, where initiation features single electron transfer from a hydroxide ion to CBr4. We now report evidence from experimental and computational studies that KOtBu and other alkoxide reagents do not go through an analogous electron transfer. Rather, the alkoxides form hypohalites upon reacting with CBr4 or CCl4, and homolytic decomposition of appropriate hypohalites initiates the halogenation of adamantane.
- Emery, Katie J.,Young, Allan,Arokianathar, J. Norman,Tuttle, Tell,Murphy, John A.
-
supporting information
(2018/05/22)
-
- SULFONAMIDE ANALOGUES OF GALIELLALACTONE
-
Disclosed are sulfonamide analogues of galiellactone of formula (I) as STAT3-inhibitors for use in the treatment of a STAT3 signaling related disorder, e.g. solid cancers, hematological cancers, benign tumors, hyperproliferative diseases, inflammations, autoimmune diseases, graft or transplant rejections, delayed physiological function of grafts or transplants, neurodegenerative diseases and viral infections. The sulfonamide comprises a cyclic substituent.
- -
-
Page/Page column 43
(2018/06/30)
-
- A head cefoxitin acid synthesis method
-
The invention discloses a synthetic method of cefoxitin acid. Cephalotin acid used as a raw material reacts with prepared tert-butyl hypochlorite in the presence of sodium methylate to obtain a methoxy substance; the methoxy substance is subjected to a hydrolysis reaction and salt formation is carried out in the presence of benzathine to obtain methoxy cefalotin benzathine; methoxy cefalotin benzathine reacts with CSI, and hydrolysis is carried out to obtain a cefoxitin acid crude product; and the cefoxitin acid crude product undergoes the step of recrystallization to finally prepare cefoxitin acid. The synthetic method is simple to operate and is low-cost. By the synthetic method, quality and total yield reach 95.8%. The produced cefoxitin acid is a white solid powder, and purity of the product reaches more than 99.0%. The product has good quality and is suitable for industrial production.
- -
-
Paragraph 0026-0028
(2017/07/06)
-
- Total Synthesis and Biological Assessment of Novel Albicidins Discovered by Mass Spectrometric Networking
-
Natural products represent an important source of potential novel antimicrobial drug leads. Low production by microorganisms in cell culture often delays the structural elucidation or even prevents a timely discovery. Starting from the anti-Gram-negative antibacterial compound albicidin produced by Xanthomonas albilineans, we describe a bioactivity-guided approach combined with non-targeted tandem mass spectrometry and spectral (molecular) networking for the discovery of novel antimicrobial compounds. We report eight new natural albicidin derivatives, four of which bear a β-methoxy cyanoalanine or β-methoxy asparagine as the central α-amino acid. We present the total synthesis of these albicidins, which facilitated the unambiguous determination of the (2 S,3 R)-stereoconfiguration which is complemented by the assessment of the stereochemistry on antibacterial activity.
- von Eckardstein, Leonard,Petras, Daniel,Dang, Tam,Cociancich, Stéphane,Sabri, Souhir,Gr?tz, Stefan,Kerwat, Dennis,Seidel, Maria,Pesic, Alexander,Dorrestein, Pieter C.,Royer, Monique,Weston, John B.,Süssmuth, Roderich D.
-
supporting information
p. 15316 - 15321
(2017/10/20)
-
- Copper-Catalyzed Synthesis of γ-Amino Acids Featuring Quaternary Stereocenters
-
The first general asymmetric synthesis of γ,γ-disubstituted γ-amino acids by copper-catalyzed ring opening of nonstrained lactones with amines is reported. This approach features ample scope, operational simplicity, and wide functional-group diversity. The catalytic process allows access to a series of highly functionalized enantioenriched γ-amino acids featuring quaternary stereocenters with excellent enantiomeric ratios of up to 98:2 and excellent yields of up to 98 %.
- Gómez, José Enrique,Guo, Wusheng,Gaspa, Silvia,Kleij, Arjan W.
-
supporting information
p. 15035 - 15038
(2017/11/20)
-
- Concise Total Synthesis of (?)-Affinisine Oxindole, (+)-Isoalstonisine, (+)-Alstofoline, (?)-Macrogentine, (+)-Na-Demethylalstonisine, (?)-Alstonoxine A, and (+)-Alstonisine
-
A highly enantio- and diastereoselective strategy to access any member of the sarpagine/macroline family of oxindole alkaloids via internal asymmetric induction was developed from readily available d-(+)-tryptophan. At the center of this approach was the diastereospecific generation of the spiro[pyrrolidine-3,3′-oxindole] moiety at an early stage via a tert-butyl hypochlorite-promoted oxidative rearrangement of a chiral tetrahydro-β-carboline derivative. This key branching point determined the spatial configuration at the C-7 spiro center to be entirely 7R or 7S. Other key stereospecific processes were the asymmetric Pictet–Spengler reaction and Dieckmann cyclization, which were scalable to the 600 and 150 gram levels, respectively. Execution of this approach resulted in first enantiospecific total synthesis of (+)-isoalstonisine and (?)-macrogentine from the chitosenine series (7R), as well as (+)-alstonisine, (+)-alstofoline, (?)-alstonoxine A and (+)-Na-demethylalstonisine from the alstonisine series (7S).
- Stephen, Michael Rajesh,Rahman, M. Toufiqur,Tiruveedhula, V. V. N. Phani Babu,Fonseca, German O.,Deschamps, Jeffrey R.,Cook, James M.
-
supporting information
p. 15805 - 15819
(2017/10/23)
-
- Asymmetric synthesis of new antimalarial aminoquinolines through Sharpless aminohydroxylation
-
Recently, the asymmetric synthesis and biological activity of (R)- and (S)-4-aminoquinolinemethanols 1 as mefloquine analogues were reported. Several compounds showed very promising antimalarial activity, in the nanomolar range, against Plasmodium falciparum 3D7 and W2. Enantiomers with an (S)-absolute configuration were more active than their (R)-counterparts by a factor ranging from 2 to 15-fold, according to the compound and the plasmodial strain considered. In continuation of our work, three novel series of enantiopure aminoquinolines 2a, 2b, and 3 were synthesized via an asymmetric aminohydroxylation reaction. These compounds were obtained in 2 or 4 steps from a common amidoalcohol key-intermediate 4. They displayed IC50 values close to the micromolar against the two P. falciparum strains 3D7 and W2. The study of the structure-activity relationships allows us to better understand the importance of the substitution and of the stereochemistry at C11 and C12 position of the quinoline and gives tracks for the design of new compounds more active against the plasmodial strains.
- Bentzinger, Guillaume,De Souza, Wesley,Mullié, Catherine,Agnamey, Patrice,Dassonville-Klimpt, Alexandra,Sonnet, Pascal
-
-
- PKC-EPSILON INHIBITORS
-
The present invention relates to new AGC kinase inhibitors, in particular to compounds of Formula I or II or a stereoisomer, tautomer, racemic, metabolite, pro- or pre-drug, salt, hydrate, or solvate thereof, wherein Ar, Cy, R1, R3, p and n have the meaning defined in the claims. In particular, the present invention relates to more specifically AGC kinases inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease.
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-
Page/Page column 73
(2016/02/28)
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- Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
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Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5-isoxazoles, furoxans, and furazans. Several of these compounds maintain low-micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.
- Florence, Gordon J.,Fraser, Andrew L.,Gould, Eoin R.,King, Elizabeth F.,Menzies, Stefanie K.,Morris, Joanne C.,Thomson, Marie I.,Tulloch, Lindsay B.,Zacharova, Marija K.,Smith, Terry K.
-
supporting information
p. 1503 - 1506
(2016/08/31)
-
- NOVEL COMPOUNDS
-
The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein L, X, Ra, Rb, R1, R2 and R3 are as defined in the specification, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
- -
-
Paragraph 0752-0753
(2015/09/22)
-
- Reactions of chlorination with tert-butyl hypochlorite (TBuOCl)
-
The chlorination reactions of nitrogenous organic compounds (2,2,2-trifluoroethylamine, benzylamine, glycine, and dimethylamine) by tert-butyl hypochlorite (tBuOCl) were studied at 25°C, ionic strength 0.5 M and under isolation conditions. The kinetic results obtained in the formation processes of the corresponding N-chloramines in acid medium (pH = 5-7) are summarized in this paper. Kinetic studies showed a first order with respect to tBuOCl concentration. The chlorination reactions involving benzylamine, glycine and dimethylamine were all first order with respect to nitrogenous compound concentration and approximately -1 order with respect to proton concentration. The reaction with 2,2,2-trifluoroethylamine was more complex, and the order of reaction with respect to the amine varied with pH.
- Pastoriza, Cristina,Antelo, Juan Manuel,Crugeiras, Juan
-
p. 952 - 959
(2015/08/25)
-
- PKC-epsilon inhibitors
-
The present invention relates to new AGC kinase inhibitors, in particular to compounds of Formula I or II or a stereoisomer, tautomer, racemic, metabolite, pro- or pre-drug, salt, hydrate, or solvate thereof, wherein Ar, Cy, R1, R3, p and n have the meaning defined in the claims. In particular, the present invention relates to more specifically AGC kinases inhibitors, compositions, in particular pharmaceuticals, comprising such inhibitors, and to uses of such inhibitors in the treatment and prophylaxis of disease.
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-
Page/Page column 77
(2014/08/06)
-
- Reactions of chlorination with tert-butyl hypochlorite (TBuOCl)
-
The chlorination reactions of nitrogenous organic compounds (2,2,2-trifluoroethylamine, benzylamine, glycine, and dimethylamine) by tert-butyl hypochlorite (tBuOCl) were studied at 25°C, ionic strength 0.5 M and under isolation conditions. The kinetic results obtained in the formation processes of the corresponding N-chloramines in acid medium (pH = 5-7) are summarized in this paper. Kinetic studies showed a first order with respect to tBuOCl concentration. The chlorination reactions involving benzylamine, glycine and dimethylamine were all first order with respect to nitrogenous compound concentration and approximately -1 order with respect to proton concentration. The reaction with 2,2,2-trifluoroethylamine was more complex, and the order of reaction with respect to the amine varied with pH.
- Pastoriza, Cristina,Antelo, Juan Manuel,Crugeiras, Juan
-
p. 952 - 959
(2015/02/19)
-
- Total synthesis of (-)-platensimycin by advancing oxocarbenium- and iminium-mediated catalytic methods
-
(-)-Platensimycin is a potent inhibitor of fatty acid synthase that holds promise in the treatment of metabolic disorders (e.g., diabetes and "fatty liver") and pathogenic infections (e.g., those caused by drug-resistant bacteria). Herein, we describe its total synthesis through a four-step preparation of the aromatic amine fragment and an improved stereocontrolled assembly of the ketolide fragment, (-)-platensic acid. Key synthetic advances include 1) a modified Lieben haloform reaction to directly convert an aryl methyl ketone into its methyl ester within 30 seconds, 2) an experimentally improved dialkylation protocol to form platensic acid, 3) a sterically controlled chemo- and diastereoselective organocatalytic conjugate reduction of a spiro-cyclized cyclohexadienone by using the trifluoroacetic acid salt of α-amino di-tert-butyl malonate, 4) a tetrabutylammonium fluoride promoted spiro-alkylative para dearomatization of a free phenol to assemble the cagelike ketolide core with the moderate leaving-group ability of an early tosylate intermediate, and 5) a bismuth(III)-catalyzed Friedel-Crafts cyclization of a free lactol, with LiClO4 as an additive to liberate a more active oxocarbenium perchlorate species and suppress the Lewis basicity of the sulfonyloxy group. The longest linear sequence is 21 steps with an overall yield of 3.8% from commercially available eugenol. Relay tactics: The stereocontrolled assembly of the potent antibiotic (-)-platensimycin in 21 steps and 3.8% yield from eugenol is described (see scheme; TBAF: tetrabutylammonium fluoride; Ts: toluene-4-sulfonyl). Highlights are 1) a rapid oxidative esterification of an acyl aromatic, 2) a reliable dialkylation protocol to form platensic acid, 3) a π-facial conjugate reduction of a dienone, 4) a TBAF-promoted alkylative dearomatization of a free phenol, and 5) a Friedel-Crafts closure of a free lactol.
- Eey, Stanley T.-C.,Lear, Martin J.
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p. 11556 - 11573
(2015/01/16)
-
- Oxidation of bromide by tert-butyl hypochlorite
-
The kinetics of the oxidation reaction of bromide by tert-butyl hypochlorite (tBuOCl) was studied at 25°C, ionic strength 0.5 M, and under isolation conditions. A stopped-flow spectrophotometer was employed for monitoring the reactions. Kinetic studies show that the reaction is first order with respect to [Br-] and [tBuOCl]. Linear dependences of the proton concentration, in perchloric acid medium, and the buffer solution concentration were found on the rate constant. The activation parameters were calculated using the Arrhenius and Eyring equations from the kinetic studies performed to analyze the influence of temperature on the rate constant. The results are consistent with a reaction mechanism of general acid catalysis. The catalytic constants were obtained for the oxidation of bromide by tert-butyl hypochlorite. The slope obtained for the Broensted relationship was 0.36.
- Pastoriza, Cristina,Antelo, Juan Manuel,Crugeiras, Juan
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p. 629 - 637
(2013/09/23)
-
- Total synthesis of alotaketal A
-
The total synthesis of the cAMP signaling pathway activator (-)-alotaketal A is reported. A convergent approach to the unusual alotane sesterterpenoid skeleton was employed, exploiting a remarkable LiDBB-mediated coupling of an (R)-carvone-derived δ-lactone with an allyl bromide side chain, followed by spiroacetalization.
- Xuan, Mengyang,Paterson, Ian,Dalby, Stephen M.
-
supporting information
p. 5492 - 5495,4
(2012/12/12)
-
- Total synthesis of alotaketal A
-
The total synthesis of the cAMP signaling pathway activator (-)-alotaketal A is reported. A convergent approach to the unusual alotane sesterterpenoid skeleton was employed, exploiting a remarkable LiDBB-mediated coupling of an (R)-carvone-derived δ-lactone with an allyl bromide side chain, followed by spiroacetalization.
- Xuan, Mengyang,Paterson, Ian,Dalby, Stephen M.
-
supporting information
p. 5492 - 5495
(2013/01/15)
-
- Total synthesis of bafilomycin A1
-
A convergent synthesis of bafilomycin A1, a potent inhibitor of V-type ATPases, is presented. The synthesis relies on the zinc triflate mediated diastereoselective addition of a complex enyne to a sensitive aldehyde as the key fragment coupling. A ruthenium-catalyzed trans-reduction of the resulting propargylic enyne efficiently installs the required C10-C13 trans,trans-diene subunit, implementing an alternative strategy to traditional palladium-catalyzed cross-coupling strategies. A highly selective oxidation of a secondary hydroxyl group in a triol sets the stage for the completion of the synthesis. Copyright
- Kleinbeck, Florian,Fettes, Gabriela J.,Fader, Lee D.,Carreira, Erick M.
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supporting information; experimental part
p. 3598 - 3610
(2012/05/04)
-
- Cytotoxic ring A-modified steroid analogues derived from Grundmann's ketone
-
A series of steroid and azasteroid analogues containing a six-membered ring A with various functionalities were synthesized. Furthermore, the syntheses of tetracyclic analogues bearing a five-membered A-ring and the syntheses of a number of bicyclic secosteroid analogues were carried out. All compounds were tested for their antibacterial, antifungal and cytotoxic activities. Among all tested compounds 7 and 9 showed outstanding cytotoxic activities but were devoid of antimicrobial activities. The cytotoxic activities of compounds 7, 9 and 10 were initially verified by the National Cancer Institute (NCI) in a one-dose 60 cell assay. In accordance with our results 7 and 9 satisfied pre-determined threshold inhibition criteria for progression to the 5-dose NCI screening, which revealed a selective activity profile for both candidates.
- Mayer, Christoph D.,Bracher, Franz
-
experimental part
p. 3227 - 3236
(2011/08/03)
-
- α-Azido bisphosphonates: Synthesis and nucleotide analogues
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The first examples of α-azido bisphosphonates [(RO) 2P(O)]2CXN3 (1, R = i-Pr, X = Me; 2, R = i-Pr, X = H; 3, R = H, X = Me; 4, R = H, X = H) and corresponding β,γ- CXN3 dGTP (5-6) and α,β-CXN3 dATP (7-8) analogues are described. The individual diastereomers of 7 (7a/b) were obtained by HPLC separation of the dADP synthetic precursor (14a/b).
- Chamberlain, Brian T.,Upton, Thomas G.,Kashemirov, Boris A.,McKenna, Charles E.
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experimental part
p. 5132 - 5136
(2011/08/09)
-
- Synthesis of 3-heteroaryloxindoles through t-BuOCl-mediated oxidation of 3-heteroarylindoles
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The oxidation of 3-heteroarylindoles to the corresponding oxindoles with t-butyl hypochlorite has been investigated. Under carefully adjusted conditions, preparative scale of desired products can be achieved. Two competing pathways seem to contribute to the reaction mechanism, affording 3-heteroaryloxindoles bearing hydrogen or chlorine at C3, depending on stereoelectronic factors. The present methodology appears also generally applicable for the preparation of simple 3-aryloxindoles. Georg Thieme Verlag Stuttgart - New York.
- Baroni, Marco,Lesma, Giordano,Puleio, Letizia,Sacchetti, Alessandro,Silvani, Alessandra,Zanchet, Marco
-
experimental part
p. 4075 - 4081
(2011/02/21)
-
- STABILIZED AND ACTIVATED BROMINE SOLUTIONS AS A BIOCIDE AND AS AN ANTIFOULING AGENT
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The invention provides a process of removing or preventing biofouling, particularly on surfaces of industrial and agricultural equipment in contact with aqueous liquids. The process employs an antifouling composition of stabilized active halogen having a low pH.
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Page/Page column 35
(2010/12/29)
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- Catalytic asymmetric allylic and homoallylic diamination of terminal olefins via formal C-H activation
-
This paper describes a catalytic asymmetric diamination process for terminal olefins at allylic and homoallylic carbons via formal C-H activation using di-tert-butyldiaziridinone as nitrogen source with a catalyst generated from Pd2(dba)3 and chiral phosphorus amidite ligand. A wide variety of readily available terminal olefins can be effectively diaminated in good yields with high regio-, diastereo-, and enantioselectivities. Copyright
- Du, Haifeng,Zhao, Baoguo,Shi, Yian
-
supporting information; experimental part
p. 8590 - 8591
(2009/02/02)
-
- New spirolactams and their synthesis
-
New spirolactams of formula (I) having a benzodienone moiety and a azetidinone moiety which are highly stable due to pi interactions. They are useful as UV absorbers and as synthetic intermediates.
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-
Page/Page column 11
(2008/06/13)
-
- Spirolactams and their synthesis
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New spirolactams having a benzodienone moiety and a azetidinone moiety which are highly stable due to pi interactions. They are useful as UV absorbers and as synthetic intermediates.
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-
-
- Efficient acyclic stereocontrol using the tethered aminohydroxylation reaction
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(Matrix Presented) The tethered aminohydroxylation (TA) of acyclic allylic carbamates has been achieved in a stereospecific and stereoselective manner. Unusually high levels of stereocontrol were observed in the oxidation of 1,1-disubstituted substrates.
- Donohoe, Timothy J.,Johnson, Peter D.,Pye, Richard J.,Keenan, Martine
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p. 2583 - 2585
(2007/10/03)
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- Biomimetic synthesis of fused polypyrans: Oxacyclization stereo- and regioselectivity is a function of the nucleophile
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(Matrix presented) The stereoselectivity of Lewis acid-induced endo-regioselective oxacyclizations of 1,4-diepoxides is dependent upon the nature of the terminating nucleophile. For instance, the tert-butyl carbonate-substituted diepoxide of 3,6-dimethylhepta-2,5-dien-1-ol provides a cis-fused bicyclic product, whereas the N,N-dimethylcarbamate derivative affords the trans-fused diastereomer. Stereospecific and regioselective conversion of the tertiary carbamate-terminated 1,4,7-triepoxide (I) to tricyclic all-trans-fused polypyran (II) is also demonstrated.
- Bravo, Fernando,McDonald, Frank E.,Neiwert, Wade A.,Do, Bao,Hardcastle, Kenneth I.
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p. 2123 - 2126
(2007/10/03)
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- Kinetics of chlorination of phenol and monosubstituted phenols by t-butyl hypochlorite in aqueous alkaline medium
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The kinetics of chlorination of the parent and sixteen monosubstituted phenols (2-chloro, 2-methyl, 2-carboxy, 2-nitro, 3-chloro, 3-methyl, 3-carboxy, 4-fluoro, 4-chloro, 4-bromo, 4-methyl, 4-ethyl, 4-methoxy, 4-carboxy, 4-acetyl and 4-nitro) by t-BuOCl have been studied in aqueous alkaline medium. The rates of reactions show first order kinetics each in |t-BuOCl| and |XC 6H4OH| and inverse first order in |OH-|. Variation in either ionic strength or addition of reaction product has no significant effect on the rates of reactions, while lowering of the dielectric constant of the medium increases the rate. The rates are measured at different temperatures and the activation parameters for all the phenols computed. A mechanism involving the electrophilic attack of phenoxide ions by HOCl in the rate determining step is suggested. The rates decrease in the order: 3-CH 3 > 2-CH3 > 4-OCH3 > 4-CH3 > 4-C2H5 > H > 3-Cl > 3-COO- > 4-F > 2-COO- > 4-Br > 2-Cl > 4-Cl > 4-COO- > 4-COCH3 > 2-NO2 > 4-NO2. Hammett equation of the type, log k = -3.44 - 2.35 ρ is found to be valid for substituent effects. The enthalpy and entropy of activation are correlated.
- Moodithaya,Gowda, B. Thimme
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p. 420 - 425
(2007/10/03)
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- Kinetics and mechanism of oxidation of aldehydes by t-butyl hypochlorite in aqueous acetic acid medium
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Kinetics of oxidation of formaldehyde, acetaldehyde, propionaldehyde and butyraldehyde by t-butyl hypochlorite have been investigated in aqueous acetic acid at 308 K. The reactions show first order kinetics in [t,BuOCl], fractional order in [aldehyde] and zero order in [H+]. Variation in ionic strength of the medium and addition of reduced products, t-butyl alcohol (0- 0.05 mol dm-3) have negligible effects on the rate, while lowering of dielectric constant of the medium by the addition of AcOH (20-60%, v/v) decreases the rate. Competitive mechanism involving substrate independent and dependent pathways has been suggested. The constancy of the rate coefficient for the substrate independent paths provides evidence for the proposed mechanism.
- Gowda, B. Thimme,Moodithaya
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p. 194 - 196
(2008/04/18)
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- 8alpha-ACYLAMINO ERGOLINES AND USE AS PHARMACEUTICAL AGENTS
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8α-acylamino ergolines are useful dopamine agonists.
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- Method for the selective alpha halogenation of alkylaromatic compounds
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Inorganic and organic hypohalites are used to obtain good selectivity to alpha halogenation of alkyl aromatic compounds. Alkali and alkaline earth hypohalites must be used in conjunction with a phase transfer medium. Useful organic hypohalites are the tertiary alkyl hypohalites, which are employed in the presence of free radical generating media such as light or compounds which produce free radicals thermally. At least one mole of hypohalite reactant must be used for every alpha hydrogen in the alkyl aromatic compound. A new bisphenol which contains biphenyl functionality has been made as well as an aromatic polyester derived therefrom.
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- Cyclodehydration and Chlorination of Simple Diols with Triphenylphosphine and tert-Butyl Hypochlorite
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The reagent triphenylphosphine-tert-butyl hypochlorite converts 1,4-diols into the corresponding tetrahydrofurans and 1,2-diols into a mixture of the regioisomeric chlorohydrins and the epoxides at -78 deg C followed by warming to ambient temperature (ca. 30 deg C).Symmetrical diols give largely chlorohydrins and dichlorides.
- Barry, Carey N.,Evans, Slayton A.
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p. 2825 - 2828
(2007/10/02)
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- Nitrobenzotrichloride or bromide process
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In the hypohalite halogenation in a two phase aqueous/organic solvent medium of a mono- or dichloro- or bromo-methylnitrobenzene to a corresponding trihalomethylnitrobenzene, the improvement wherein the reaction is conducted in the presence of a phase transfer catalyst or where the organic phase is a C4 to C8 alkanol.
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