- Nano Ag/AgCl wires-photocatalyzed hydrogen production and transfer hydrogenation of Knoevenagel-type products
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An investigation of the relationship between the morphology of Ag/AgCl nanostructured composites with their catalytic performance has been reported. The concentration ratio of silver nitrate and hydrochloric acid was controlled to produce Ag/AgCl nanowires (NWs) and nanospheres (NSs). The catalytic activity of the photoresponsive NWs was evaluated towards methylene blue (MB) dye degradation and hydrogen production and showed high performance compared to the NSs under visible light irradiation. It was estimated that the NWs produced hydrogen at a rate approximately 2.27 times faster than the NSs. Additionally, the catalytic properties of the as-synthesized nanomaterials were examined in the transfer hydrogenation of the carbon-carbon double bonds (CC) present in Knoevenagel-type products (trisubstituted alkenes) through exciting the surface plasmons of the NWs and NSs with a catalyst loading of 5 wt% under visible light irradiation. Again, it was revealed that the Ag/AgCl NWs showed increased activity to produce the reduced adducts in a higher yield, with a 95% isolated yield compared to that obtained in the case of the use of Ag/AgCl NSs, which afforded products in a 62% isolated yield. Further investigation was carried on the catalytic performance of the Ag/AgCl NWs in the one-pot synthesis of trimethoprim, a known antibiotic, which was afforded in an 86% yield through two consecutive steps in a tandem process. It was clearly shown from the results that the photocatalytic activity of the prepared Ag/AgCl nanoparticles depends on their morphology. This journal is
- Attia, Yasser A.,Mohamed, Yasser M. A.
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p. 1677 - 1686
(2022/02/05)
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- METHODS AND COMPOSITIONS FOR OPTOCHEMICAL CONTROL OF CRISPR-CAS9
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The disclosure includes non-naturally occurring or engineered DNA- or RNA-guided nuclease systems, comprising CRISPR enzymes associated with at least one destabilization domain (DD) and photocaged stabilization ligands with at least one photocage molecule, along with compositions, systems and complexes involving such systems, nucleic acid molecules and vectors encoding the same, delivery systems involving the same, uses thereof.
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Paragraph 0044
(2021/10/15)
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- A Singular System with Precise Dosing and Spatiotemporal Control of CRISPR-Cas9
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Several genome engineering applications of CRISPR-Cas9, an RNA-guided DNA endonuclease, require precision control of Cas9 activity over dosage, timing, and targeted site in an organism. While some control of Cas9 activity over dose and time have been achieved using small molecules, and spatial control using light, no singular system with control over all the three attributes exists. Furthermore, the reported small-molecule systems lack wide dynamic range, have background activity in the absence of the small-molecule controller, and are not biologically inert, while the optogenetic systems require prolonged exposure to high-intensity light. We previously reported a small-molecule-controlled Cas9 system with some dosage and temporal control. By photocaging this Cas9 activator to render it biologically inert and photoactivatable, and employing next-generation protein engineering approaches, we have built a system with a wide dynamic range, low background, and fast photoactivation using a low-intensity light while rendering the small-molecule activator biologically inert. We anticipate these precision controls will propel the development of practical applications of Cas9.
- Manna, Debasish,Maji, Basudeb,Gangopadhyay, Soumyashree A.,Cox, Kurt J.,Zhou, Qingxuan,Law, Benjamin K.,Mazitschek, Ralph,Choudhary, Amit
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p. 6285 - 6289
(2019/04/08)
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- Synthetic method of trimethoprim
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The invention discloses a synthetic method of trimethoprim. Trimethoprim is synthesized from 3,4,5-trimethoxybenzaldehyde and ethyl cyanoacetate. The method has the advantages of high conversion rate, short time, and industrial production facilitation.
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- Practical preparation of trimethoprim: A classical antibacterial agent
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An efficient, simple, and mild preparation of the classical antibacterial agent trimethoprim (1) was achieved in 85% overall yield from 3,4,5-trimethoxybenzaldehyde (2). First, the addition of propenenitrile (3) with dimethylamine almost quantitatively afforded 3-dimethylaminopropanenitrile (7). Then, by condensation of 7 with 2 as well as the continuous replacement of 3-dimethylamino group with aniline in situ, the key intermediate 3-anilino-2-(3,4,5-trimethoxybenzyl)propenenitrile (9) was obtained in an excellent yield of 91% with a one-pot procedure. Finally, the cyclization of 9 with guanidine nitrate furnished 1 in yields as good as 95% in the presence of the excessive sodium methoxide. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications1 to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Ji, Ya-Fei,Jiang, Jian-An,Liu, Hong-Wei,Liao, Dao-Hua,Wei, Xian-Yong
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p. 1517 - 1522
(2013/05/22)
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- Immobilization of malarial (Plasmodium falciparum) dihydrofolate reductase for the selection of tight-binding inhibitors from combinatorial library
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A simple procedure for selection of tight-binding inhibitors of mutant dihydrofolate reductases from Plasmodium falciparum (PfDHFRs) based on preferential binding to the enzyme immobilized on a Sepharose column has been described. PfDHFRs with a cysteine residue at the C-terminal have been prepared in order to immobilize to a thiopropyl-Sepharose gel via S-S linkage. The amount of immobilized DHFRs was estimated to be 4-5 mg/g of dried gel, and the activities of bound DHFRs were comparable to that of free enzymes. The prepared immobilized enzyme has been used for the selection of tight-binding inhibitors from combinatorial libraries, based on the affinities of each ligand with the enzyme. Free ligands were then identified and analyzed quantitatively by high-performance liquid chromatography-mass spectrometry, and the components with high binding affinity of the library could thus be realized. Results could be confirmed by quantitative analysis of the bound ligands released from the enzyme by guanidine hydrochloride treatment.
- Thongpanchang, Chawanee,Taweechai, Supannee,Kamchonwongpaisan, Sumalee,Yuthavong, Yongyuth,Thebtaranonth, Yodhathai
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p. 5006 - 5012
(2008/02/08)
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- Synthesis of functionalized diarylmethanes via a copper-catalyzed cross-coupling of arylmagnesium reagents with benzylic phosphates
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A combination of copper chloride, triethyl phosphite, and tetrabutylammonium iodide is a very efficient catalytic system for the synthesis of polyfunctionalized diarylmethanes, using the cross-coupling reaction of arylmagnesium halides with benzylic phosphates. The antibiotic Trimethoprim has been prepared using this Cu(I)-catalyzed cross-coupling in 52% overall yield (four steps).
- Kofink, Christiane C.,Knochel, Paul
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p. 4121 - 4124
(2007/10/03)
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- Development of 2,4-diaminopyrimidines as antimalarials based on inhibition of the S108N and C59R+S108N mutants of dihydrofolate reductase from pyrimethamine resistant Plasmodium falciparum
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The reduced binding of pyrimethamine to Serl08Asn (S108N) mutants of parasite dihydrofolate reductase (DHFR), which forms the basis of resistance of Plasmodium falciparum to pyrimethamine, is largely due to steric constraint imposed by the bulky side chain of N108 on Cl of the 5-p-Cl-phenyl group. This and other S108 mutants with bulky side chains all showed reduced binding to pyrimethamine and cycloguanil. Less effect on binding to some bulky mutants was observed for trimethoprim, with greater flexibility for the 5-substituent. S108N DHFR also binds poorly with other pyrimethamine derivatives with bulky groups in place of the p-Cl, and the binding was generally progressively poorer for the double (C59R+S108N) mutant. Removal of the p-Cl or replacement with m-Cl led to better binding with the mutant DHFRs. Pyrimethamine analogues with unbranched hydrophobic 6-substituents showed generally good binding with the mutant DHFRs. A number of compounds were identified with high affinities for both wild-type and mutant DHFRs, with very low to no affinity to human DHFR. Some of these compounds show good antimalarial activities against pyrimethamine-resistant P. falciparum containing the mutant DHFRs with low cytotoxicity to three mammalian cell lines.
- Tarnchompoo, Bongkoch,Sirichaiwat, Chawanee,Phupong, Worrapong,Intaraudom, Chakapong,Sirawaraporn, Worachart,Kamchonwongpaisan, Sumalee,Vanichtanankul, Jarunee,Thebtaranonth, Yodhathai,Yuthavong, Yongyuth
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p. 1244 - 1252
(2007/10/03)
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- An efficient benzyltriethylammonium chloride catalysed preparation of electrophilic alkenes: a practical synthesis of trimethoprim
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The Knoevenagel condensation of carbonyl compounds with active methylene compounds was readily carried out with benzyltriethylammonium chloride as a catalytic agent, under solvent-free conditions to produce olefinic products in high yeilds: the scope of this protocol is utilised for the synthesis of the antibacterial agent trimethoprim.
- Bose, D. Subhas,Narsaiah, A. Venkat
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- A New Route To Antibacterial Trimethoprim
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3-Methylthio-2-(3',4',5'-trimethoxybenzyl)acrylonitrile (6) derived from 3,4,5-trimethoxyphenylacetaldehyde (2) in a four step sequence was utilized as a new three carbon unit of trimethoprim (1).
- Harada, Kenichi,Choshi, Tominari,Sugino, Eiichi,Sato, Kohichi,Hibino, Satoshi
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p. 1119 - 1126
(2007/10/02)
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- Metelation of diazines VIII metalation of 4-chloropyrimidine derivatives new synthesis of trimethoprim
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A new synthesis of trimethoprim is described, metalation of a pyrimidine has been used in the key step. An exceptional regioselectivity in the metalation of pyrimidine derivatives has been highlighted.
- Ple,Turck,Martin,Barbey,Queguiner
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p. 1605 - 1608
(2007/10/02)
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- Syntheses of Antibacterial 2,4-Diamino-5-benzylpyrimidines. Ormetoprim and Trimethoprim
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A general and mild method for the synthesis of 2,4-diamino-5-benzylpyrimidines was achieved by the Friedel-Crafts reaction between 2-(methoxymethylene)-3-methoxypropanenitrile (10) and an activated aromatic substrate followed by treatment with guanidine.The method is illustrated by a synthesis of ormetoprim (2) in 75percent overall yield from 3,4-dimethoxytoluene (12).Efficient syntheses of trimethoprim (1) and 2 were also accomplished via prior base-catalyzed 1,3-prototropic isomerization of cinnamonitriles 19 and 20, respectively, followed by condensation with guanidine. 12 was prepared from 3-bromo-4-methoxytoluene by a Cu(I)-catalyzed displacement of bromine by methoxide and 4,5-dimethoxy-2-methylbenzaldehyde was obtained from 12 in 87percent yield by a pyridine-catalyzed Vilsmeier reaction using DMF-POCl3.
- Manchand, Percy S.,Rosen, Perry,Belica, Peter S.,Oliva, Gloria V.,Perrotta, Agostino V.,Wong, Harry S.
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p. 3531 - 3535
(2007/10/02)
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- Process for the preparation of 2,4-diamino-5-benzylpyrimidines
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The invention relates to a process for the preparaton of compounds of the formula I by reacting an alkali metal alcoholate with a compound of the formula II in the presence of an aliphatic ester such as methyl formate, and then condensing guanidine with the resulting compound of the formula III. The compound of the formula II can be prepared by reacting the corresponding benzaldehyde with acrylonitrile in the presence of diazabicyclo-2,2,2,-octane. STR1
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- 6-Azaoligocycloalkylmethyleneaminopenam compounds
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6-Amino-penam compounds, having an antimicrobial action, of the formula STR1 in which R1 is an azaoligocycloalkyl radical which is bonded via the ring nitrogen atom and contains at least one endo-bridge atom and a total of 7 to 12 ring atoms and can contain a double bond and/or, if desired, as a further ring hetero-atom, an oxygen atom, or a nitrogen atom which can link the radical X1, where X1 is hydrogen or lower alkyl, and/or, if desired, free, esterified or etherified hydroxyl which is bonded to a ring carbon atom, and in which R2 is free carboxyl or carboxyl esterified by a physiologically detachable group, and salts of such compounds, processes for their preparation, pharmaceutical preparations which contain these compounds, including mixtures of these compounds with other antimicrobial, especially antibacterial and/or antiviral, active ingredients and/or additional substances or substance mixtures which alleviate the symptoms in the case of infections, the use of the novel compounds of the formula I and their salts, and of the novel substance mixtures, for combating micro-organisms and the preparation of corresponding medicaments by non-chemical means.
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- 2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. II. C-alkylation of pyrimidines with Mannich bases and application to the synthesis of trimethoprim and analogues
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A new route to 5-(p-hydroxybenzyl)pyrimidines has been developed which utilizes phenolic Mannich bases plus pyrimidines containing at least two activating groups. The products can be alkylated on the phenolic oxygen or on the pyrimidine N-1 atom, depending on conditions. This method has been used to prepare trimethoprim, a broad-spectrum antibacterial agent, starting from 2,4-diaminopyrimidine and 2,6-dimethoxyphenol.
- Roth,Strelitz,Rauckmann
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p. 379 - 384
(2007/10/02)
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- 2,4-Diamino-5-benzylpyrimidines as Antibacterial Agents. 4. 6-Substituted Trimethoprim Derivatives from Phenolic Mannich Inetrmediates. Application to the Synthesis of Trimethoprim and 3,5-Dialkylbenzyl Analogues
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The preparation of a wide variety of 6-substituted trimethoprim analogues was readily accomplished by the reaction of 2,4-diamino-6-substituted-pyrimidines with 2,6-dimethoxy-4-phenol at 120-160 deg C.The less reactive 2,6-dialkyl-4-phenols reacted successfully with 2,4-diamino-6-(alkylthio)pyrimidines to give 5-(substituted benzyl)pyrimidines.The phenolic groups of the products were alkylated in high yield when a nonreactive 6-substituent was present in the pyrimidine ring. 6-(Alkylthio) groups were easily removed with Raney nickel.Trimethoprim was thus obtained in high yield from its 6-(methylthio) counterpart.The 6-substituted trimethoprim analogues all had low activity as inhibitors of Escherichia coli dihydrofolate reductase and as antibacterial agents.
- Roth, Barbara,Aig, Edward,Lane, Kenneth,Rauckman, Barbara S.
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p. 535 - 541
(2007/10/02)
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- Benzyl cyanoacetals
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Benzyl cyanoacetals of formula: STR1 wherein R1, R2 and R3 are the same or different and each is a halogen or a hydrogen atom, an alkoxy group, an alkyl group, or a dialkylamino group; R4 is an alkoxycarbonyl group, or an aldehyde group; And R5 is an alkyl group; the alkyl or alkoxy groups each having from 1 to 4 carbon atoms, and their use as intermediates in the preparation of antibacterial 2,4-diamino-5-benzylpyrimidines. They are prepared from a reaction between an orthoester and an α-substituted-β-benzylpropionitrile and then the resulting cyanoacetal is converted to the benzyl-pyrimidine by reaction with guanidine.
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- Process for the production of 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine
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A process for the production of 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine by condensing trimethoxy benzaldehyde with a substituted propionitrile compound and reacting the condensation product obtained with guanidine, wherein a β-akyl-(aryl-, benzyl-)-oxy-ethyleneoxy-propionitrile corresponding to the formula in which R represents an alkyl group, an optionally substituted phenyl group or a benzyl group, is condensed with trimethoxy benzaldehyde in the presence of Basic reagents to form a compound corresponding to the general formula STR1 in which R is as defined above, and the condensation product (II) obtained is reacted with guanidine in known manner to form 2,4-diamino-5-(3',4',5'-trimethoxybenzyl)-pyrimidine.
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- Process for preparing 2,4-diamino-5-(substituted benzyl)-pyrimidines
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2,4-Diaminopyrimidines bearing a substituted benzyl group in position-1 are prepared from the correspondingly substituted α-alkoxymethylcinnamonitrile by treatment of the latter with an alkali metal alkoxide in mono-methyl ether of ethylene glycol and subsequently reacting the resulting reaction mixture with guanidine.
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- Preparation of β-anilino-α-benzylacrylonitriles
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Compounds comprising selected N-substituted β-amino-α-benzyl-acrylonitriles and methods of preparing said compounds substantially free from the corresponding bensalacrylonitrile. The compounds are useful as intermediates in the preparation of antibacterial and antimalerial agents.
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- 3-Imino-1,2,4-benzotriazine-1-oxides
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New 3-Imino-1,2,4-benzotriazine-1-oxides of formula I SPC1 wherein R represents an alkyl, alkenyl or haloalkyl radical, a phenyl or aralkyl radical optionally substituted by alkyl, alkoxy, haloalkyl, halogen or hydroxy, X and Y each independently represent hydrogen, halogen, an alkyl or alkoxy radical, or one of the two symbols represents a phenoxy or phenylsulphonyl radical optionally substituted by halogen, alkyl, haloalkyl and/or alkoxy which are active against harmful microorganisms are disclosed.
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