- 1,2,2-Tribromocyclopropanecarboxylic acid and derivatives - Valuable intermediates for four carbon cyclopropane and cyclopropene synthons
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Methyl 1,1,2-tribromocyclopropanecarboxylate is readily available by dibromocyclopropanation of methyl α-bromoacrylate. Reaction with methyllithium at low temperature provides a simple route to methyl 2-bromocyclopropene carboxylate, while modification of the ester group followed by reaction with methyllithium leads to a series of related four-carbon cyclopropenes. The tribromo-ester is also readily converted into 1,1,2,2-tetrabromocyclopropane, a valuable three-carbon cyclopropene synthon.
- Al Dulayymi, Ahmad R.,Al Dulayymi, Juma'a R.,Baird, Mark S.,Gerrard, Michelle E.,Koza, Gani,Harkins, Samantha D.,Roberts, Evan
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- COMPOUNDS AND METHODS FOR TREATMENT OF BACTERIAL INFECTIONS
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This document discloses a novel class of compounds for inhibiting bacterial growth and treating bacterial infection. The compounds target a key step of the futalosine pathway and therefore are effective for the selective inhibition of certain bacterial species and genera with reduced side effect in comparison with conventional antibiotics.
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Paragraph 0079
(2020/12/07)
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- Chemoselective Synthesis of N-Terminal Cysteinyl Thioesters via β,γ-C,S Thiol-Michael Addition
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Dehydroalanine (ΔAla) is a highly electrophilic residue that can react efficiently with sulfur nucleophiles to furnish cysteinyl analogues. Herein, we report an efficient synthesis of N-terminal cysteinyl thioesters, suitable for S,N-acyl transfer, based on β,γ-C,S thiol-Michael addition. Both ionic and radical-based methodologies were found to be efficient for this process.
- Petracca, Rita,Bowen, Katherine A.,McSweeney, Lauren,O'Flaherty, Siobhan,Genna, Vito,Twamley, Brendan,Devocelle, Marc,Scanlan, Eoin M.
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supporting information
p. 3281 - 3285
(2019/05/10)
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- Using bar infrared spectra and coincidence indexes to study the diversity of solid cyanuric acid structures
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A general method was developed for studying the diversity of individuals in a population based on the diversity of infrared spectra of solid cyanuric acid analytes obtained from various reactions of trichlorocyanuric acid. This method first generates infrared bar spectra for the analytes and then measures the coincidence and continence among pairs of the spectral peaks via confrontation matrices. Class markers are established to characterize analyte classes. Possible correlations among the employed reaction conditions and the nature of the produced solids, which are based on their infrared bar spectra, are discussed. The method of coincidence may be useful for characterizing polymorphs, particularly those of active pharmaceutical ingredients (APIs). The method may also be extended to define the homogeneity of solid analytes. The ANALIN module of the ANALOR software suite running on a dBase platform is used to generate the bar infrared spectra and to handle all calculations.
- Nilo, Marcela C. B. G.,Sim?es, Thais G.,Neto, Claudio Costa
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p. 1499 - 1515
(2018/06/12)
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- How Reaction Conditions May Influence the Regioselectivity in the Synthesis of 2,3-Dihydro-1,4-benzoxathiine Derivatives
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The exploration of different reaction conditions aiming to obtain both 2,3-dihydro-1,4-benzoxathiine-2-yl derivatives and 2,3-dihydro-1,4-benzoxathiine-3-yl ones is reported. The treatment of 1,2-mercaptophenol with an organic base and a specific 2-bromo acrylate results in a solvent- and substrate-dependent exclusive solvation of O- and S-anions, thus managing the regioselectivity.
- Casiraghi, Andrea,Valoti, Ermanno,Suigo, Lorenzo,Artasensi, Angelica,Sorvillo, Erica,Straniero, Valentina
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p. 13217 - 13227
(2018/10/24)
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- Targeting Alzheimer's disease by investigating previously unexplored chemical space surrounding the cholinesterase inhibitor donepezil
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A series of twenty seven acetylcholinesterase inhibitors, as potential agents for the treatment of Alzheimer's disease, were designed and synthesised based upon previously unexplored chemical space surrounding the molecular skeleton of the drug donepezil, which is currently used for the management of mild to severe Alzheimer's disease. Two series of analogues were prepared, the first looking at the replacement of the piperidine ring in donepezil with different sized saturated N-containing ring systems and the second looking at the introduction of different linkers between the indanone and piperidine rings in donepezil. The most active analogue 5,6-dimethoxy-1-oxo-2,3-dihydro-1H-inden-2-yl 1-benzylpiperidine-4-carboxylate (67) afforded an in vitro IC50value of 0.03 ± 0.07 μM against acetylcholinesterase with no cytotoxicity observed (IC50of >100 μM, SH-SY5Y cell line). In comparison donepezil had an IC50of 0.05 ± 0.06 μM and an observed cytotoxicity IC50of 15.54 ± 1.12 μM. Molecular modelling showed a strong correlation between activity and in silico binding in the active site of acetylcholinesterase.
- van Greunen, Divan G.,Cordier, Werner,Nell, Margo,van der Westhuyzen, Chris,Steenkamp, Vanessa,Panayides, Jenny-Lee,Riley, Darren L.
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p. 671 - 690
(2017/02/10)
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- One-Pot Strategy for Thiazoline Synthesis from Alkenes and Thioamides
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A convenient synthesis of a privileged pharmaceutical motif, thiazoline is accomplished. This reaction utilizes simple and readily available alkene and thioamide substrates in an intermolecular fashion via a simple one-pot procedure. A wide range of functional groups is tolerated, and the thiazoline product has been further utilized for the synthesis of the corresponding β-aminothiol and thiazole from routine hydrolysis and oxidation protocols.
- Alom, Nur-E,Wu, Fan,Li, Wei
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supporting information
p. 930 - 933
(2017/02/26)
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- Synthesis method of O-methyl-D-serine
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The invention discloses a synthesis method of O-methyl-D-serine. The synthesis method includes the following steps that 1, acrylic acid methyl ester is added into a reaction bottle, after the temperature is raised, bromine is dropwise added, after an addition reaction is conducted, decompression and distillation are conducted to remove excessive bromine, methyl alcohol is added to residues, after the temperature is lowered, sodium methylate is added, after an alcoholysis reaction, decompression and distillation are conducted to remove methyl alcohol, ammonium hydroxide is added, after an ammonium hydroxide, concentrated crystallization is conducted, and O-methyl-DL-serine is obtained; 2, acetic acid is added into the reaction bottle, the O-methyl-DL-serine, D-tartaric acid and salicylaldehyde are added in sequence, after the temperature is raised for a reaction, cooling and crystallization are conducted, separation is conducted, and O-methyl-D-serine double salt is obtained; 3, the O-methyl-D-serine double salt is dissolved in a methyl alcohol aqueous solution, ammonium hydroxide is added to regulate PH to be 7-8, crystallization and separation are conducted, and the O-methyl-D-serine is obtained. The synthesis method is mild in reaction temperature, safe to operate, low in cost and high in chirality purity, and raw materials are easy to obtain.
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Paragraph 0041
(2017/01/02)
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- Synthesis and biological evaluation of a series of benzoxazole/ benzothiazole-containing 2,3-dihydrobenzo[b][1,4]dioxine derivatives as potential antidepressants
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A series of benzoxazole/benzothiazole-2,3-dihydrobenzo[b][1,4]dioxine derivatives (5a-5d and 8a-8j) was synthesized. Compounds were evaluated for binding affinities at the 5-HT1A and 5-HT2A receptors. Antidepressant activities of the compounds were screened using the forced swimming test (FST) and the tail suspension test (TST). The results indicated that the compounds exhibited high affinities for the 5-HT1A and 5-HT2A receptors and showed a marked antidepressant-like activity. Compound 8g exhibited high affinities for the 5-HT1A (Ki = 17 nM) and 5-HT2A (Ki = 0.71 nM) receptors; it also produced a decrease of the immobility time and exhibited potent antidepressant-like effects in the FST and TST in mice.
- Wang, Songlin,Chen, Yin,Zhao, Song,Xu, Xiangqing,Liu, Xin,Liu, Bi-Feng,Zhang, Guisen
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p. 1766 - 1770
(2014/04/17)
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- A PROCESS FOR PREPARING TRIAZOLE COMPOUNDS
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The present invention relates to process for preparing triazole compounds used in the treatment of epilepsy. The process comprises of reacting compound of 2, 6 difluoroazide (II) with 2, 3 dihalo compound (III) to form compound of formula I, which on further treatment with an aminating agent gives Rufinamide (IV). 2, 6 difluoroazide (II) is reacted with 2, 3 dihalo compound (III) in the presence of a solvent. The reaction can be carried out in a single pot without isolation of intermediates.
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Page/Page column 17
(2014/05/24)
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- NEW PROCESS
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There is provided a process for the preparation of Lacosamide in a particular polymorphic form, which process involves the isolation of a salt of formula I : according to the methods defined in the application.
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Page/Page column 38
(2014/05/24)
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- Chemoenzymatic synthesis of piperoxan, prosympal, dibozane, and doxazosin
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The synthesis of both enantiomers of 1,4-benzodioxan-2-carboxylic acid 1, a key synthetic intermediate for the therapeutic agents piperoxan, prosympal, dibozane, and doxazosin was achieved with good yields and high enantioselectivities via the Arthrobacter sp. lipase catalyzed kinetic resolution of ester (±)-17a. The influence of the co-solvents and the immobilization of the lipase upon kinetic resolution demonstrated that immobilized whole cells, in the presence of n-butanol as a co-solvent, resulted in the optimal resolution of the substrate (ee ～99%, E = 535) at 258 mmol (50 g/L) substrate concentration.
- Rouf, Abdul,Gupta, Pankaj,Aga, Mushtaq A.,Kumar, Brijesh,Chaubey, Asha,Parshad, Rajinder,Taneja, Subhash C.
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p. 1615 - 1623
(2013/02/22)
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- Anionic [4+3] heteroannulation of 2-azidoacrylates: A modular synthesis of 2-benzazepin-1-ones
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2-Azidoacrylates undergo [4+3] annulation with phthalides under anionic conditions at low temperatures to furnish 5-hydroxy-2-benzazepinones, the formation of which represents a new concept for the construction of azepines as well as a new reactivity of 2-azidoacrylates.
- Dinda, Bidyut Kumar,Jana, Amit Kumar,Mal, Dipakranjan
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supporting information; experimental part
p. 3999 - 4001
(2012/06/01)
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- Robust eco-friendly protocol for the preparation of γ-hydroxy- α,β-acetylenic esters by sequential one-pot elimination-addition of 2-bromoacrylates to aldehydes promoted by LTMP in 2-MeTHF
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An efficient and widely applicable preparation of γ-hydroxy-α, β-acetylenic esters is described by means of a one-pot dehydrobromination of a 2-bromoacrylate ester with LTMP followed by the electrophilic addition of the transient propiolate to different aldehydes in the eco-friendly solvent 2-MeTHF. The Royal Society of Chemistry 2012.
- Pace, Vittorio,Castoldi, Laura,Alcantara, Andres R.,Holzer, Wolfgang
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supporting information; experimental part
p. 1859 - 1863
(2012/08/14)
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- Efficient access to isoxazoles from alkenes
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The direct regioselective synthesis of 3,5-disubstituted isoxazoles was achieved in one reaction vessel through a sequence of reactions involving the net bromination of an electron-deficient alkene, in situ generation of a nitrile oxide, 1,3-dipolar cycloaddition, and loss of HBr from an intermediate 5,5-disubstituted bromoisoxazoline. This one-pot process enables the synthesis of 3,5-disubstituted isoxazoles directly from electron-deficient alkenes thereby negating the isolation of the 1,1-disubstituted bromoalkene alkyne surrogate. Georg Thieme Verlag Stuttgart.
- Xu, Jianping,Hamme II, Ashton T.
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p. 919 - 923
(2008/12/22)
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- Synthetic cofactor analogs of S-adenosylmethionine as ligatable probes of biological methylation and methods for their use
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The present invention discloses compounds and methods used to specifically target substrates of methylation by S-adenosyl-L-methionine (SAM)-dependent methyltransferases. The substrates can be peptides, single stranded nucleic acids or double stranded nucleic acids, including RNA, DNA and PNA or phospholipids. The compounds disclosed are SAM analogs that are ligated to a methylation site by the methyltransferase. Also disclosed, are reacting groups that are ligatable to the cofactor analogs and can also be used as detectable labels. The reacting group can be used to cleave the substrate providing a methylation footprint. The invention can be used clinically to determine methylation state of a gene or gene promoter such as those involved in imprinting and transcription. In some preferred embodiments, the invention includes a kit, which can include one or more suitable SAM analogs and may include one or more detectable labels. In other preferred embodiments, the invention includes a pharmaceutical composition.
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- An economical and convenient synthesis of vinyl sulfones
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A general process for the efficient synthesis of vinyl sulfones has been developed using commercially available sulfinic acid sodium salts and dibromides. A variety of phenyl and methyl vinyl sulfones have been formed in good yields, in the absence of any catalyst. Georg Thieme Verlag Stuttgart.
- Guan, Zheng-Hui,Zuo, Wei,Zhao, Lian-Biao,Ren, Zhi-Hui,Liang, Yong-Min
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p. 1465 - 1470
(2008/02/05)
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- Efficient synthesis of highly functionalized cyclic aminimides
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(Chemical Equation Presented) Simple condensation reactions of various α,β-epoxy or α,β-aziridinyl methyl esters with 1,1-dialkyl hydrazines provided cyclic aminimides (1,1-dialkyl-3-oxopyrazolidines) with a heteroatom substituent at the 4-position in good yields. The reaction proceeds smoothly, without any coreagent, providing the product as an easily isolable precipitate. The reaction is expected to be a good candidate for combinatorial synthesis of a highly functionalized five-membered ring scaffold. The scope and limitations of this reaction were investigated by varying the substituents R1-R5.
- Moon, Bongjin,Han, Sangbae,Kim, Dohyung
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p. 3359 - 3361
(2007/10/03)
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- (Diacetoxyiodo)benzene-Lithium Bromide as a Convenient Electrophilic Br+ Source
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A mild and versatile procedure for the bromination of olefins and activated arenes by in situ generation of 'Br+' using (diacetoxyiodo)benzene and lithium bromide is presented. The reactions were carried out in open vessels at room temperature and were typically complete in 30 minutes. The brominated products were isolated by column chromatography, which also allowed for the isolation of the iodobenzene by-product for recycle.
- Braddock, D. Christopher,Cansell, Gemma,Hermitage, Stephen A.
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p. 461 - 464
(2007/10/03)
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- Conformational Stability, Barriers to Internal Rotation, Vibrational Assignment, and RHF/STO-3G* Calculations of 2-Bromopropenoyl Fluoride
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The far-infrared spectrum of gaseous 2-bromopropenoyl fluoride, CH2CBrCFO, has been recorded at a resolution of 0.10 cm-1 in the region 350-35 cm-1.The fundamental asymmetric torsional frequencies of the more stable s-trans (two double bonds oriented trans to one another) and the high-energy s-cis conformations have been observed at 61.90 and 44.27 cm-1, respectively, each with several excited states appearing at lower frequencies.From these data, the asymmetric torsional potential function governing internal rotation about the C-C bond has been determined.The potential coefficients are V1 = -17 +/- 12, V2 = 1506 +/- 48, V3 = 321 +/- 19, V4 = -43 +/- 14, and V5 = -48 +/- 7 cm-1.The s-trans-s-cis and s-cis-s-trans barriers have been determined to be 1684 +/- 35 and 1428 +/- 21 cm-1, respectively, with an energy difference between the conformations of 256 +/- 79 cm-1 (732 +/- 226 cal/mol).From studies of the Raman spectrum at variable temperatures, the conformational enthalpy difference has been determined to be 247 +/- 60 cm-1 (706 +/- 172 cal/mol) and 340 +/- 22 cm-1 (972 +/- 63 cal/mol) for the gas and liquid, respectively.A complete assignment of the vibrational fundamentals observed from the infrared spectra (3500-50 cm-1) of the gas and solid and the Raman spectra (3200-10 cm-1) of all three physical states is proposed.All of these data are compared to the corresponding quantities obtained from ab initio Hartree-Fock gradient calculations employing the STO-3G* basis set.The results are discussed and compared with the corresponding quantities obtained for some similar molecules.
- Durig, J. R.,Wang, Ai-Ying,Little, T. S.,Brletic, P. A.
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p. 3569 - 3578
(2007/10/02)
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- REACTIONS OF HALOGEN FLUORIDES XII. REACTION OF BROMINE TRIFLUORIDE WITH BROMINE-CONTAINING ESTERS. A NEW METHOD FOR THE SYNTHESIS OF FLUOROALKYL 2-FLUOROACRYLATES
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Being weak Lewis bases, esters reduce the reactivity of bromine trifluoride in the substitutive fluorination of organic bromine derivatives.For this reason the rate of the reaction of bromine trifluoride with bromine-containing esters depends not only on the electronic characteristics of the substituents at the reaction center but also on the basicity of the ester.As a rule, the selectivity of the reaction increases with increase in the basicity of the ester.The reaction of bromine trifluoride or chlorine monofluoride with fluoroalkyl 2,3-dibromopropionates can be used successfully for the synthesis of monomers (fluoroalkyl 2-fluoroacrylates).
- Kartashov, A. V.,Chuvatkin, N. N.,Boguslavskaya, L. S.
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p. 2243 - 2248
(2007/10/02)
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- Rearrangement of a Bicyclic System to a Bicyclic System. Nonclassical Ions
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The syntheses and the establishment of the absolute configurations of chiral (S)-(+)-2-bromodibenzobicyclooctadiene-2-carboxylic acid (1) and (1S,2S,5S)-(-)-exo-2-methoxydibenzobicyclooctadiene-1-carboxylic acid (2) and their derivatives are described.The rearrangement of 1 to 2 is discussed in terms of a nonclassical ion intermediate in light of the observed stereochemistry.
- Rachon, Janusz,Goedken, V.,Walborsky, H. M.
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p. 1006 - 1012
(2007/10/02)
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- DIENOPHILIE DES OLEFINES CAPTODATIVES - VI SYNTHESES ET CYCLOADDITIONS DE DIELS-ALDER DES α-ALKYLTHIO-ACRYLATES D'ALKYLE AVEC LE CYCLOPENTADIENE: INFLUENCE DES FACTEURS STERIQUES SUR LA REACTIVITE ET SUR LA STEREOSELECTIVITE
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The Diels-Alder reactions of cyclopentadiene with a series of four α-alkylthio-alkyl acrylates were investigated.Although slightly slower than the reactions of unsubstituted alkyl acrylates, the spontaneous cycloadditions of these captodative olefins occur at room temperature affording adducts in excellent yield.The steric effect of the ester function is found to be more important in determining the dienophilic reactivity than the endo/exo ratios of the adducts and increase in the size of the alkylthio group reduces the endo selectivity of that group from 66-69percent (for methylthio) to 25-22percent (for tertiobutylthio group).The aluminium trichloride complexed methoxycarbonyl group leads to a very high endo-stereoselectivity (97percent) of that group.
- Boucher, Jean-Luc,Stella, Lucien
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p. 3595 - 3606
(2007/10/02)
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- An Improved Synthesis of 3-(1-Imidazolyl)-2-alkenoic Acid Derivatives and Related Compounds
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The preparative method of 3-(1-imidazolyl)-2-alkenoic acid derivatives and the related compounds was improved by the use of strong bases such as sodium hydride in DMF.By this improved method, the preparation of 2-substituted 3-(1-imidazolyl)-2-alkenoic acid derivatives was accomplished in good yields.
- Kashima, Choji,Yoshiwara, Nobutoshi,Tajima, Tadakuni,Omote, Yoshimori
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p. 1595 - 1596
(2007/10/02)
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- Kinetics and Mechanism of Bromine Addition to Derivatives of Unsaturated Aliphatic Carboxylic Acids in Aqueous Solution
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This paper deals with the kinetics of bromine addition to unsaturated compounds in presence of added bromide ions at 22, 30, 38, 46, and 54 deg C.The substrates used were acrylamide (AAm), methyl acrylate (MA), ethyl acrylate (EA), butyl acrylate (BA), t-butyl acrylate (tBA), methacrylamide (MAAm), methyl methacrylate (MMA), ethyl methacrylate (EMA), methyl crotonate (MC), and ethyl crotonate (EC).The kinetics was followed potentiometrically.The activation parameters (ΔH*, ΔS*, and ΔG*) were calculated and compared.Estimation of product ratio of bromohydrin to dibromide showed the absence of any correlation of the product formation with reactivity of the substrates.The observed parameters are discussed in relation to the proposed reaction mechanisms.
- Mohamed Farook, Syed Ahamed,Viswanathan, Seshaiyer,Ganesan, Ramachandran
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p. 1394 - 1400
(2007/10/02)
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- The Compounds Related to 3-(1-Imidazolyl)-2-alken-1-ones. Preparation and Reactions
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Compounds related to 3-(1-imidazolyl)-2-alken-1-ones, 3-(1-imidazolyl)-2-alkenoic acid derivatives and 2-alken-1-ones having heterocycles on the C-3 carbon were prepared.The reaction of nucleophiles with these compounds was also discussed.
- Kashima, Choji,Tajima, Tadakuni,Omote, Yoshimori
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p. 171 - 176
(2007/10/02)
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- Carbon-13 NMR Spectra of Bromine-containing Esters
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13CHBrCOOR fragments of bromine-containing mono- and dicarboxylates show 13C NMR signals in the range 38-45 ppm, at 12-15 ppm to high field of their chloro analogues.The introduction of one bromine atom into the α-CH2 group causes a 6-13 ppm shift of the carbon signal, depending on the type of ester.The replacement of H with Br in 13C2H2(COOR)2 has only a negligible influence on the 13CH2 signal position.The 13CBr2COOR fragment signals appear in the range 40-54 ppm. 13C NMR data, including the chemical shift values, signal multiplicities and spin-spin couplings, make possible the identification of isomers present in isomer mixtures of bromine-containing esters.The 13COOR chemical shifts of diastereomers of α,β-dibromoesters differ noticeably from each other, and the 13C NMR spectra can thus be used to supply preliminary information about the stereochemistry of bromine addition to α,β-unsaturated acids.
- Velichko, F. K.,Dostovalova, V. I.,Vinogradova, L. V.,Freidlina, R Kh.
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p. 442 - 446
(2007/10/02)
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- INHIBITORY OCTAPEPTIDES ANGIOTENSIN II
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Octapeptide derivatives characterized by an oxygen or sulfur-containing moiety in the C-terminal position are potent inhibitors of the pharmacological effects of Angiotensin and possess the additional advantage of a favorable antagonist/agonist ratio.
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