- SYSTEMS AND METHODS FOR DETECTION OF TARGET ANALYTES USING SELECTIVELY CLEAVABLE BONDS
-
The invention described herein is directed to methods of isolation and detection of target analytes in a sample. The target analytes are coupled to analyte detection particles which comprise base particles having labels and affinity agents coupled thereto by linker arms. The linker arms form bonds with the labels and target analytes and are cleavable under different label and affinity cleavable conditions. Systems and methods for preparing and using the analyte detection particles are also disclosed.
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- METHOD FOR PRODUCING BIOTIN
-
To provide a production method for obtaining high-purity biotin at good yields.SOLUTION: A method for producing biotin includes a process in which a composition comprising biotin represented by the formula (I) is brought into contact with hydrosulfite salt, before the biotin is extracted.SELECTED DRAWING: None
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Paragraph 0067-0083
(2021/02/25)
-
- Solution Dynamics of Hybrid Anderson-Evans Polyoxometalates
-
Understanding the stability and speciation of metal-oxo clusters in solution is essential for many of their applications in different areas. In particular, hybrid organic-inorganic polyoxometalates (HPOMs) have been attracting increasing attention as they combine the complementary properties of organic ligands and metal-oxygen nanoclusters. Nevertheless, the speciation and solution behavior of HPOMs have been scarcely investigated. Hence, in this work, a series of HPOMs based on the archetypical Anderson-Evans structure, δ-[MnMo6O18{(OCH2)3C-R}2]3-, with different functional groups (R = -NH2, -CH3, -NHCOCH2Cl, -NCH(2-C5H4N) {pyridine; -Pyr}, and -NHCOC9H15N2OS {biotin; -Biot}) and countercations (tetrabutylammonium {TBA}, Li, Na, and K) were synthesized, and their solution behavior was studied in detail. In aqueous solutions, decomposition of HPOMs into the free organic ligand, [MoO4]2-, and free Mn3+ was observed over time and was shown to be highly dependent on the pH, temperature, and nature of the ligand functional group but largely independent of ionic strength or the nature of the countercation. Furthermore, hydrolysis of the amide and imine bonds often present in postfunctionalized HPOMs was also observed. Hence, HPOMs were shown to exhibit highly dynamic behavior in solution, which needs to be carefully considered when designing HPOMs, particularly for biological applications.
- Salazar Marcano, David E.,Lentink, Sarah,Moussawi, Mhamad A.,Parac-Vogt, Tatjana N.
-
supporting information
p. 10215 - 10226
(2021/05/31)
-
- Selective modification of sulfamidate-containing peptides
-
Hybrid peptides whose N-terminal residues are activated in the form of α-methylisoserine-derived cyclic sulfamidates exhibit rich reactivity as electrophiles, allowing site- and stereoselective modifications at different backbone and side chain positions.
- Busto, Jesús H.,Jiménez-Osés, Gonzalo,Mazo, Nuria,Navo, Claudio D.,Peregrina, Jesús M.
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supporting information
p. 6265 - 6275
(2020/09/07)
-
- A preparation method of d - biotin (by machine translation)
-
The invention belongs to the field of organic synthesis, in particular relates to a preparation method of d - biotin, the method comprises the following steps: the double-benzyl biotin with three boron halide and organic solution, in the absence of the organic solvent in the water environment, under the protection of inert gas, through the one-step reaction to remove the double-benzyl, get d - biotin. The present invention provides a simple and convenient, safe, high yield, high purity of methylsulphonyl preparation method of d - biotin, is suitable for industrial production. (by machine translation)
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Paragraph 0037; 0038; 0039; 0040; 0041; 0042; 0043-0060
(2019/05/04)
-
- A dibenzyl biotin by d - biotin method of preparation
-
The invention discloses a method for preparing d-biotin from dibenzyl biotin. The method comprises the following steps: 1, adding an inorganic acid and zinc powder to an aqueous solution of dibenzyl biotin; and 2, reacting at 40-70DEG C, and post-processing after the raction ends to obtain d-biotin. The d-biotin is prepared through removing benzyl groups by using the zinc powder/inorganic acid system under mild conditions, so the method has the advantages of simple operation and easy industrialization; and the purity of the obtained d-biotin is greater than 99.5%, and the mole yield of the obtained d-biotin is greater than 90%, so compared with the prior art, the method has substantial progress.
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Paragraph 0033-0038
(2019/02/26)
-
- Synthesis method of d-biotin
-
The invention discloses a synthesis method of d-biotin. The synthesis method comprises the following steps: taking cysteine hydrochloride, benzaldehyde and benzyl isocyanate as starting materials, andsubjecting the starting materials to condensation, cyclization, reduction, condensation, oxidation, reduction, cyclization, elimination, catalytic hydrogenation and debenzylation sequentially to obtain the d-biotin. The method has the advantages that the raw materials are cheap and easy to obtain, the safety is good, the reaction conditions are mild and easy to control, the production cost is lowered, green and environmental protection is achieved, the reaction yield is high, separation is easy, and the purity of the obtained d-biotin is high.
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Paragraph 0109-0118
(2019/04/04)
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- Method for Producing Intermediate of Biotin and Method for Producing Biotin
-
In the method, a trione compound represented by the following formula (1) is (i) reduced by NaAlH2(OCH2CH2OCH3)2 and subsequently further reduced by a metal borohydride salt, or (ii) reduced by calcium borohydride, thereby producing an amide alcohol compound represented by the following formula (3) (wherein, R1 and R2 may be the same or different and each represents a hydrogen atom or a protecting group of an ureylene group; R4 represents an alkyl group, an aralkyl group, or an aryl group; and each of R5, R6, and R7 represents a hydrogen atom, an alkyl group, an alkoxy group, or a halogen atom).
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-
-
- Selective Modification of Ribosomally Synthesized and Post-Translationally Modified Peptides (RiPPs) through Diels–Alder Cycloadditions on Dehydroalanine Residues
-
We report the late-stage chemical modification of ribosomally synthesized and post-translationally modified peptides (RIPPs) by Diels–Alder cycloadditions to naturally occurring dehydroalanines. The tail region of the thiopeptide thiostrepton could be modified selectively and efficiently under microwave heating and transition-metal-free conditions. The Diels–Alder adducts were isolated and the different site- and endo/exo isomers were identified by 1D/2D 1H NMR. Via efficient modification of the thiopeptide nosiheptide and the lanthipeptide nisin Z the generality of the method was established. Minimum inhibitory concentration (MIC) assays of the purified thiostrepton Diels–Alder products against thiostrepton-susceptible strains displayed high activities comparable to that of native thiostrepton. These Diels–Alder products were also subjected successfully to inverse-electron-demand Diels–Alder reactions with a variety of functionalized tetrazines, demonstrating the utility of this method for labeling of RiPPs.
- de Vries, Reinder H.,Viel, Jakob H.,Oudshoorn, Ruben,Kuipers, Oscar P.,Roelfes, Gerard
-
supporting information
p. 12698 - 12702
(2019/09/12)
-
- Method for catalytic synthesis of biotin by using high-recycling-activity palladium-carbon catalyst
-
The invention discloses a method for catalytic synthesis of biotin by using a high-recycling-activity palladium-carbon catalyst. The method comprises the following steps: palladium-carbon is taken asa catalyst to catalyze synthesis of biotin by hydrogenation of a biotin intermediate cis-2-oxo-1,3-dibenzyl-4-(4-carboxybutyl-1-ene)hexahydro-1H-thieno[3,4-d]imidazole, wherein activated carbon is taken as a carrier of the catalyst, the carrier is activated by hydrogen peroxide after being subjected to high-temperature treatment in an ammonia atmosphere, and then the pretreated activated carbon isobtained; the soluble palladium compound is dissolved in water, a nitrogen-containing compound is added, and reflux stirring is carried out to obtain a palladium precursor solution; and the pretreated activated carbon is pulped by using alcohol water, then a palladium precursor solution is added, an alkali is added for controlling the pH value of the system to be 6-12, and then reduction is carried out by a reducing agent to obtain the palladium-carbon catalyst. Compared with the prior art, the method disclosed by the invention has the advantages that activity of the catalyst is high, performance of the catalyst is stable, the number of recycling times in biotin synthesis can be greatly increased, and production cost can be reduced.
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-
Paragraph 0019; 0020-0057
(2019/04/10)
-
- Method for preparing thiolactone intermediate of D-biotin
-
The invention discloses a method for preparing a thiolactone intermediate of D-biotin. The method comprises the following steps of: (a) adding a lactone intermediate and potassium thioacetate at a mass ratio of (2:1)-(2.4:1) into a reaction vessel, conducting heating until the obtained reaction system is in a completely molten state, and then performing thermal insulation and stirring for 1-5 hours; (b) cooling the reaction system to 50-80 DEG C, and then adding 2-10 ml of water per 1 gram of the lactone intermediate into the reaction system; (c) cooling the reaction system to 0-10 DEG C withstirring, then conducting thermal insulation, and keeping stirring for 1-5 hours; and (d) performing filtration, and collecting the obtained solid to obtain the thiolactone intermediate of D-biotin. Through the method, no participation of solvents in the reaction is achieved, not only can no problems of environmental protection and recovery of the solvents be generated, but also the preparation cost can be low; the operation process is low, especially, the high-purity target product with HPLC purity of 99.5% or above can be obtained only through filtration and water washing, and the mass yieldreaches 95% or above.
- -
-
Paragraph 0021-0025; 0026-0030
(2018/05/16)
-
- A dibenzyl biological the element escapes the animal pen system improved method of d - biotin
-
The invention relates to an improved method for preparing d-biotin from bisbenzyl biotin by debenzylation, which has the advantages of high product quality, low cost and high environment friendliness. The method comprises the following steps: putting bisbenzyl biotin 5-[(3aS,4S,6aR)]-1,3-dibenzyl-2-oxohexahydro-1H-thieno[3,4-d]imidazolyl-4-yl]valeric acid in a reaction kettle; adding hydrobromic acid, stirring and heating to reflux, and reacting under reflux conditions until no raw material dots by TLC (thin layer chromatography) detection; adding an aromatic solvent for extraction, and separating an organic phase from a water phase; concentrating the water phase under reduced pressure to a dry state; adding pure water, stirring, standing to crystallize, and filtering to obtain a d-biotin crystal; concentrating the filtrate, standing to crystallize, filtering to obtain a diamido substance 5-[(2S,3S,4R)-3,4-diamidotetrahydrothienyl-2-yl]valeric acid hydrobromide, adding the diamido substance and an inorganic alkali solution into a reaction kettle, and adding phosgene to carry out cyclization reaction; after the cyclization reaction finishes, regulating the pH value to acidity with an inorganic acid solution, and standing to crystallize; and filtering to obtain the d-biotin 5-[(3aS,4S,6aR)]-2-oxohexahydro-1H-thieno[3,4-d]imidazolyl-4-yl]valeric acid. The method is used for producing d-biotin from bisbenzyl biotin.
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Paragraph 0063; 0064; 0068; 0069; 0073; 0074
(2017/08/25)
-
- A debenzylation synthesis of d - biotin improved method
-
The invention discloses an improved d-biotin debenzylation synthesizing method. As for existing methods in which biotin is prepared in liquid ammonia in a debenzylation mode through metallic sodium, debenzylation can not be complete. According to the technical scheme, the method includes the steps that firstly, debenzylation is carried out on double-benzyl biotin in liquid ammonia through metallic sodium to form single-benzyl biotin; secondly, the single-benzyl biotin is reacted with silicane protective agents, and amidogen and carboxyl of the single-benzyl biotin are protected to obtain group protectors of the single-benzyl biotin; thirdly, debenzylation is carried out on the group protectors of the single-benzyl biotin in the liquid ammonia through the metallic sodium again, acid neutralization and deprotection are carried out, and complete-debenzylation crude d-biotin is obtained; finally, the crude biotin is refined to obtain the fine d-biotin. According to the method, debenzylation is almost complete, the yield of the d-biotin is high, and the method is quite suitable for industrial production.
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-
Paragraph 0012-0013; 0032-0036; 0038- 0068
(2017/09/01)
-
- A benzyl biological the element escapes the animal pen method for preparing biotin
-
The invention belongs to the technical field of fine chemical engineering, and discloses a method for preparing biotin by debenzylating benzyl biotin. The method comprises the following steps: fully dispersing dibenzyl biotin synthesized through different processes in hydrobromic acid under the assistance of a dispersant, rapidly stirring, carrying out heating distillation, condensing and layering steamed benzyl bromide and hydrobromic acid, refluxing the upper layer hydrobromic acid to a reaction solution, separating out the lower layer benzyl bromide, rapidly cooling, carrying out vacuum distillation to recover hydrobromic acid, adding a quantitative of water or a mother liquor to the above obtained residual solid, carrying out heating dissolving, adjusting the acidity, adding active carbon for decoloring, cooling for precipitating biotin crystals (87% of a theoretic amount), carrying out drying and distillation purification of benzyl bromide to obtain qualified benzyl bromide, crystallizing open ring substances residual in the mother liquor, continuously indiscriminately using the mother liquor 20 times, controlling the pH value by a liquid alkali, and carrying out ring closure of triphosgene to obtain recovered biotin. The yield of biotin is averagely improved by 5% in the invention. The method has the advantages of safety, environmental protection, high yield, good quality, low cost, and suitableness for industrialized production.
- -
-
Paragraph 0030; 0032
(2017/01/12)
-
- Preparation of (+)-biotin: Process development and scale-up
-
A practical asymmetric total synthesis of (+)-biotin based upon the chiral bifunctional sulfamide 8-promoted enantioselective anhydride desymmetrization has been achieved via the key chiral intermediacy of (3aS, 6aR)-1,3-bis(4-methoxybenzyl)tetrahydro-4H-thieno[3,4-d]imidazole-2,4(1H)-dione (4). In addition, the installation of the 4-carboxybutyl side chain at C-4 position of 4 was efficiently introduced by an improved C4+C1 strategy.
- Xiong, Fei,Li, Jin,Li, Gen,Song, Bo,Zhou, Yu-Xiao,Chen, Fen-Er,Li, Dan
-
p. 544 - 551
(2016/04/10)
-
- A method for synthesizing d-biotin
-
The invention discloses a method for synthesizing d-biotin. The method comprises the following steps: carrying out cyclization on (2S, 3S, 4S)-5-(3,4-diamido-thiophane-2-yl) valeric acid and carbonic ester under the effect of an acid catalyst; carrying out post-treatment to obtain the d-biotin after the reaction is ended, wherein the structure of the carbonic ester is shown in the specification; R and R are independently selected from C1-C5 alkyls; the acid catalyst is one or combination of more of a protonic acid and a lewis acid. By adopting the synthetic method, the carbonic ester is adopted as a reagent to replace triphosgene or diphosgene to react, and generation of a virulent phosgene intermediate is avoided, so that the method is friendlier to the environment; meanwhile, the reaction efficiency is improved by selecting a specific catalyst, and the yield of the d-biotin is increased.
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-
Paragraph 0060-0064
(2017/06/29)
-
- D-biotin a simple method for preparing
-
The invention relates to a simple method for preparing D-biotin. The method comprises the following steps: carrying out a substitution reaction between L-cysteine ester hydrochloride and 6-halogenated hexanoate (II) in the presence of an acid-binding agent, and preparing (S)-2-amino-4-sulfo-di-sebacate; preparing the (S)-2-ester group normal-butyl-4-benzylaminotetrahydrothiophene-3-ketone sulfur oxide (V) by virtue of N-benzylation, sulfide oxidation to form sulphone and intra-molecular cyclization; performing amidation cyclization and deoxidation reduction to prepare 5-(6aR1-benzyl-2-oxo-5,6-dihydrothiopheneo[3,4-d]imidazole-4-yl)valerate (VII), performing catalytic hydrogenation and hydrolysis, thereby obtaining the D-biotin. The raw materials are readily available, the reaction conditions are easy to control, the operational process is short, and the method is safe, environment-friendly and low in product cost and is suitable for industrial production.
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-
-
- A process for the preparation of biotin D-
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The invention relates to a low-consumption simple and convenient preparation method of D-biotin. The method comprises the following steps: by taking adipate diester and nitromethane as initial raw materials, condensing under the action of a strong base to form sodium 7-nitro-6-hydroxyl-6-n-heptenoate ester (II), performing cyclic condensation reaction to the compound (II) with mercaptoacetate ester and acetic acid to obtain 2-carbalkoxy-n-butyl-3-nitro-4,5-dihydrothiophene-4-one (III), dehydrating the compound (III) and benzylamine and performing reduction amination reaction with sodium acetborohydride under the catalysis of (R)-proline to obtain 4S-2-carbalkoxy-n-butyl-3-nitro-benzylamino-4,5-dihydrothiophene (IV), performing catalytic hydrogenation and hydrolysis to the compound (IV) to prepare sodium 5-(2S,3S,4R-3,4-diaminotetrahydrothiphene-2-yl)-valerate (V) aqueous solution, and finally performing cyclic amidation with solid phosgene to prepare D-biotin. According to the low-consumption simple and convenient preparation method of D-biotin, the raw materials are low in cost and easy to obtain, the reaction conditions are easy to operate, the operation flow is short, the low-consumption simple and convenient preparation method is safe and environment-friendly, and the product is low in cost and suitable for industrial production.
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-
-
- IRIDIUM-BASED COMPLEXES FOR ECL
-
The present invention relates to novel iridium-based Ir(III) luminescent complexes, conjugates comprising these complexes as a label and their application, e.g. in the electrochemiluminescence based detection of an analyte.
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-
Page/Page column
(2015/05/26)
-
- NUCLEIC ACID AMPLIFICATION AND SEQUENCING BY SYNTHESIS WITH FLUOROGENIC NUCLEOTIDES
-
In general, the invention features methods and systems for sequencing of nucleic acids based on the measurement of the incorporation of fluorogenic nucleotides in microreactors. The invention provides numerous advantages over previous systems such as unambiguous determination of sequence, fast cycle time, long read lengths, low overall cost of reagents, low instrument cost, and high throughput. The invention also features methods and kits for nucleic acid amplification. The amplification and sequencing aspects of the invention may or may not be employed in conjunction with one another. The invention also features fluorogenic nucleotides that may be used in the sequencing methods of the invention.
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Page/Page column
(2013/03/26)
-
- Highly enantioselective methanolysis of meso-cyclic anhydride mediated by bifunctional thiourea cinchona alkaloid derivatives: Access to asymmetric total synthesis of (+)-biotin
-
An enantioselective asymmetric total synthesis of (+)-biotin (1) via the Hoffmann-Roche lactone-thiolactone strategy has been accomplished from commercially available cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2). Strategic transformations include a cinchona alkaloid-based bifunctional thiourea mediated methanolytic desymmetrization of prochiral cyclic anhydride 3 to produce the enantiomerically enriched precursor of Roche lactone 5 and an improved introduction of the 4-carboxybutyl side chain at C-4 position of Roche thiolactone 6 via Grignard reaction.
- Xiong, Fei,Xiong, Fang-Jun,Chen, Wen-Xue,Jia, Hui-Qing,Chen, Fen-Er
-
p. 1078 - 1082
(2013/10/21)
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- METHOD FOR PREPARING D-BIOTIN
-
An Improved Preparation Method for D-Biotin The invention discloses an improved preparation method for D-Biotin. If the composite method takes the diesteas the raw material, the finial biotin will be generated with impurities. The features of the invention refers to the improved preparation method for D-Biotin includes: firstly, (3aS,4S,6aR)-1,3-ωωω -butyl)-1H-thiaphene[3,4-d]-2,4(1H)-ketone is got after the methane tricarboxylic acid trialkyl ester and (3aR, 8aS, 8bS)-1,3-2-[3,4-d]thiophene [1,2-a]sulfuryl halide have the condensation reaction in the alkaline environment and then D-Biotin can be got after the reaction process of hydrolysis, decarbaxylation and closed loop. The invention succeeds in greatly improving the biotin quality from the original basis and simultaneously avoids the generation of impurities and the occurrence of side reaction.
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Page/Page column 6
(2012/04/10)
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- Improved Preparation Method for D-Biotin
-
The invention discloses the improved preparation method for D-Biotin. If the composite method takes the malonic acid diester as the raw material, the finial biotin will be generated with impurities. The features of the invention refers to the improved preparation method for D-Biotin includes: firstly, (3aS,4S,6aR)-1,3-dibenzyl-4-(ω,ω,ω-3 -alkoxycarbonyl bytyl)-4H-1H-thiophene[3,4-d]iminazole-2,4(1H)-ketone is got after the methane tricarboxylic acid trialkyl ester and (3aR,8aS,8bS)-1,3-dibenzyl-2-oxo-10H-iminazole[3,4-d]thiophene[1,2-a]sulfuryl halide have the condensation reaction in the alkaline environment and then D-Biotin can be got after the reaction process of hydrolysis, decarboxylation and closed loop. The invention succeeds in greatly improving the biotin quality from the original basis and simultaneously avoids the generation of impurities and the occurrence of side reaction.
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Page/Page column 4
(2012/03/27)
-
- Synthetic studies on (+)-biotin, part 151: A chiral squaramide-mediated enantioselective alcoholysis approach toward the total synthesis of (+)-biotin
-
An efficient stereocontrolled total synthesis of (+)-biotin (1) has been achieved via the intermediacy of Roche's lactone 5 starting from cis-1,3-dibenzyl-2-imidazole-4,5-dicarboxylic acid (2). The bifunctional cinchona alkaloid-derived squaramide-promoted enantioselective alcoholysis was utilizing as a tool for the construction of two contiguous stereocenters of C-3a and C-6a in biotin molecular with excellent enantioselectivity. In addition, the 4-carboxybutyl side chain was assembled by first using C4+C1 approach via a novel tricyclic thiophanium salt intermediate.
- Chen, Xu-Xiang,Xiong, Fei,Fu, Han,Liu, Zhi-Qian,Chen, Fen-Er
-
experimental part
p. 488 - 491
(2011/05/14)
-
- An improved asymmetric total synthesis of (+)-biotin via the enantioselective desymmetrization of a meso-cyclic anhydride mediated by cinchona alkaloid-based sulfonamide
-
The highly enantioselective total synthesis of (+)-biotin 1 via the Hoffmann-Roche lactone-thiolactone strategy has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid 2 with an overall yield of 35%. Two contiguous stereogenic centers at C-3a and C-6a were established through a rapid cinchona alkaloid-based sulfonamide-mediated enantioselective alcoholysis of meso-cyclic anhydride 3 to afford (4S,5R)-cinnamyl hemiester 4h, the direct precursor to (3aS,6aR)-lactone 5 with high enantioselectivity. A one-pot installation of the 4-carboxybutyl side chain was accomplished by a Fukuyama coupling reaction of (3aS,6aR)-thiolactone 6 with the organozinc reagent prepared from ethyl 5-bromopentanoate.
- Xiong, Fei,Chen, Xu-Xiang,Chen, Fen-Er
-
experimental part
p. 665 - 669
(2010/07/17)
-
- Mild Chemically Cleavable Linker System
-
A linker system is provided where a small molecule reactive group, e.g., an activity based probe which binds to certain enzymes at the active site, is linked through an aryl diazo linker to an affinity molecule such as biotin. The reactive group may comprise a number of functionalities known to react with a specific target to be studied. This enables the probe to be exposed to analytes, such as proteins and bind specifically to them to form a complex having an affinity molecule allowing immobilization of the bound analyte on an affinity column or other support, e.g. with streptavidin. Then, the linker is cleaved without causing removal of the affinity group or dissociation of the probe from the analyte. The linker is cleaved under mild reducing conditions, e.g., dithionite. The probe is synthesized along with the linker on a solid support.
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-
- Chemical Reporters of Protein Acylation
-
Methods and kits for detecting acylated proteins produced by cells that have been cultured or by cells within an organism are provided. Also provided are methods and kits for detecting acylated proteins produced by cells where affinity purification tags are that facilitate detection are used. Compounds useful for the detection of acylated proteins are also provided.
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-
- Biotin derivatives carrying two chelating DOTA units. Synthesis, in vitro evaluation of biotinidases resistance, avidin binding, and radiolabeling tests
-
The synthesis of four biotin derivatives carrying two DOTA moieties for each ligand (BisDOTA set) is reported, for increasing radiation/dose ratio and improving efficiency in the pretargeted avidin-biotin radioimmunotherapy. The biotin-containing scaffold of two BisDOTAwas similar to the mono-DOTA derivative previously described. Then the scaffold was elongated by trifunctionalized spacers of different length and conjugated with one of the COOH groups of two DOTA. Two others were prepared starting from a on-resin lysine residue. The lysine R-NH2 was bonded to biotin, and then spacers were appended to the ε-NH2 and conjugated with two DOTA molecules. One compound contained a p-aminobenzoic acid spacer, which ensured higher head-to-tail distance and increased rigidity of the chain. These last two compounds had a very high ability to bond avidin and were labeled with 90Y at high specific activity. All the compounds were resistant to the action of serum biotinidases. 2009 American Chemical Society.
- Pratesi, Alessandro,Bucelli, Francesca,Mori, Ilaria,Chinol, Marco,Verdoliva, Antonio,Paganelli, Giovanni,Rivieccio, Vincenzo,Gariboldi, Lucia,Ginanneschi, Mauro
-
experimental part
p. 432 - 440
(2010/06/11)
-
- A novel synthetic strategy for the stereospecific total synthesis of (±)-biotin
-
A concise and efficient TEA-mediated desymmetrization of meso-thioanhydride 6 with 5-ethoxy-5-oxopentylzinc bromine has been developed, which affords a convenient strategy for the stereospecific total synthesis of (±)-biotin 1.
- Xiong, Fei,Chen, Xu-Xiang,Liu, Zhi-Qian,Chen, Fen-Er
-
body text
p. 3670 - 3672
(2010/08/20)
-
- Structural characterization of the mycobacterium tuberculosis biotin biosynthesis enzymes 7,8-diaminopelargonic acid synthase and dethiobiotin synthetase
-
Mycobacterium tuberculosis (Mtb) depends on biotin synthesis for survival during infection. In the absence of biotin, disruption of the biotin biosynthesis pathway results in cell death rather than growth arrest, an unusual phenotype for an Mtb auxotroph. Humans lack the enzymes for biotin production, making the proteins of this essential Mtb pathway promising drug targets. To this end, we have determined the crystal structures of the second and third enzymes of the Mtb biotin biosynthetic pathway, 7,8-diaminopelargonic acid synthase (DAPAS) and dethiobiotin synthetase (DTBS), at respective resolutions of 2.2 and 1.85 A. Superimposition of the DAPAS structures bound either to the SAM analogue sinefungin or to 7-keto-8-aminopelargonic acid (KAPA) allowed us to map the putative binding site for the substrates and to propose a mechanism by which the enzyme accommodates their disparate structures. Comparison of the DTBS structures bound to the substrate 7,8-diaminopelargonic acid (DAPA) or to ADP and the product dethiobiotin (DTB) permitted derivation of an enzyme mechanism. There are significant differences between the Mtb enzymes and those of other organisms; the Bacillus subtilis DAPAS, presented here at a high resolution of 2.2 A, has active site variations and the Escherichia coli and Helicobacter pylori DTBS have alterations in their overall folds. We have begun to exploit the unique characteristics of the Mtb structures to design specific inhibitors against the biotin biosynthesis pathway in Mtb.
- Dey, Sanghamitra,Lane, James M.,Lee, Richard E.,Rubin, Eric J.,Sacchettini, James C.
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p. 6746 - 6760
(2011/04/26)
-
- PROCESS FOR THE MANUFACTURE OF (+)-BIOTIN
-
Disclosed are processes for preparing synthetic biotin intermediates and a process for preparing biotin using said intermediates. In particular, disclosed is a process for the stereoselective total synthesis of the natural product (+)-biotin of formula (I).
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Page/Page column 37-38
(2009/05/28)
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- Total synthesis of (+)-biotin via a quinine-mediated asymmetric alcoholysis of meso-cyclic anhydride strategy
-
A concise asymmetric total synthesis of (+)-biotin 1 has been accomplished in which the absolute stereochemistry of C3a, C6a of 1 was established by utilizing an efficient and practical quinine-mediated asymmetric alcoholysis of meso-cyclic anhydride 2 in a single step, the C4 stereochemistry was installed by a direct stereoselective ionic hydrogenation of the thiolactol 7.
- Huang, Jian,Xiong, Fei,Chen, Fen-Er
-
p. 1435 - 1442
(2008/12/20)
-
- Biochemical method for specific protein labeling
-
An improved method for protein labeling comprising the steps of providing a synthetic small molecule tag, providing a target protein to be tagged, providing at least two enzymes for catalyzing a conjugation reaction between the tag and the target protein, incubating the tag, the protein and the enzyme, and allowing the tag to conjugate to the target protein. The tag may embody at least one structural feature of an ubiquitin C-terminus, and the structural feature may comprise a recognition sequence that is recognizable by an ubiquitin activating enzyme.
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- Synthetic studies on (+)-biotin, Part 11:[1] Application of Cinchona alkaloid-mediated asymmetric alcoholysis of meso-cyclic anhydride in the total synthesis of (+)-biotin
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A practical and asymmetric process for the totalsyn thesis of (+)-biotin (1) has been accomplished starting from cis-1,3-dibenzyl-2-oxoimidazolidine-4,5- dicarboxylic acid (2). This approach features a highly enantioselective alcoholysis of mesocyclic anhydride 3 into (4S,5R)-cinnamylhemiest er 4 mediated by Cinchona alkaloids. Another attractive feature of this synthesis involves the use of recyclable palladium nanoparticles-catalyzed assembly of the 4-carboxybutyl chain at C-4 in (3aS,6aR)-thiolactone 7 employing an improved Fukuyamatype cross-coupling reaction.
- Dai, Hui-Fang,Chen, Wen-Xue,Zhao, Lei,Xiong, Fei,Sheng, Hao,Chen, Fen-Er
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experimental part
p. 1635 - 1641
(2009/07/18)
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- Diastereoselective amidoalkylation of (3S,7aR)-6-benzyl-7-hydroxy-3- phenyltetrahydro-5H-imidazo[1,5-c][1,3]thiazol-5-one: A short and highly efficient synthesis of (+)-biotin
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(Chemical Equation Presented) A short and highly efficient synthesis of (+)-biotin in 10 steps with 20% overall yield has been achieved from L-cysteine involving amidoalkylation of hydroxy imidazothiazolone 4 via an acyliminium ion intermediate to furnish C-7-substituted imidazothiazolones 5b as the key step.
- Chavan, Subhash P.,Chittiboyina, Amar G.,Ravindranathan,Kamat, Subhash K.,Kalkote, Uttam R.
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p. 1901 - 1903
(2007/10/03)
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- An unusual stereochemical outcome of radical cyclization: Synthesis of (+)-biotin
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An enantioselective synthesis of (+)-biotin 1 starting from naturally available cysteine is described. The key steps are the unusual stereochemical outcome of radical cyclization of compound 10 to prepare 5,5-fused system 11, and the introduction of C4-sidechain at C6 in 13 via a Grignard reaction.
- Chavan, Subhash P.,Chittiboyina, Amar G.,Ramakrishna, Guduru,Tejwani, Rajkumar B.,Ravindranathan,Kamat, Subhash K.,Rai, Beena,Sivadasan, Latha,Balakrishnan, Kamalam,Ramalingam,Deshpande
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p. 9273 - 9280
(2007/10/03)
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- Synthetic studies on d-biotin, part 8: An efficient chemoenzymatic approach to the asymmetric total synthesis of d-biotin via a polymer-supported PLE-mediated desymmetrization of meso-symmetic dicarboxylic esters
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A practical chemoenzymatic method for the asymmetric total synthesis of d-biotin (1) starting from the commercially available cis-1,3-dibenzyl-2- imidazolidone-4,5-dicarboxylic acid (2) has been developed. The key step of the synthesis is the highly enantioselective hydrolysis of meso-dicarboxylic esters by a polymer-supported pig liver esterase and introduction of a formyl group at the C-4 position in 4 via a Grignard reaction. The polymer-supported PLE can be recovered quantitatively from the reaction mixture by simple filtration and reused without significant loss of activity.
- Chen, Fen-Er,Chen, Xu-Xiang,Dai, Hui-Fang,Kuang, Yun-Yan,Xie, Bin,Zhao, Jian-Feng
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p. 549 - 554
(2007/10/03)
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- Nucleic acid labeling compounds
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Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.
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- Synthetic studies on d-biotin, part 9.1) An improved asymmetric synthetic route to d-biotin via Hoffmann-Roche lactone-thiolactone approach
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An efficient and highly stereoselective total synthesis of d-biotin has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (2) with an overall yield of 33%. Polymer-supported oxazaborolidine- catalyzed asymmetric reduction of meso-cyclic imide 4 constitutes the key synthetic step in introducing stereogenic centers into the d-biotin molecule.
- Chen, Fen-Er,Jia, Hui-Qing,Chen, Xu-Xiang,Dai, Hui-Fang,Xie, Bin,Kuang, Yun-Yan,Zhao, Jian-Feng
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p. 743 - 746
(2007/10/03)
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- A practical synthesis of (+)-biotin from L-cysteine
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α-Amino aldehyde 4, which is readily derived from L-cysteine through cyclization and elaboration of the carboxy group, was subjected to the Strecker reaction, which, via sodium bisulfite adduct 16, afforded α-amino nitrile 5 with high diastereose-lectivity (syn/anti = 11:1) and in high yield. Amide 6, derived from 5, was converted to thiolactone 8, a key intermediate in the synthesis of (+)-biotin (1), by a novel S,N-carbonyl migration and cyclization reaction. The Fukuyama coupling reaction of 8 with the zinc reagent 21, which has an ester group, in the presence of a heterogeneous Pd/ C catalyst allowed the efficient installation of the 4-carboxybutyl chain to provide 9. Compound 9 was hydrogenated and the protecting groups removed to furnish 1 in 10 steps and in 34 % overall yield from L-cysteine.
- Seki, Masahiko,Hatsuda, Masanori,Mori, Yoshikazu,Yoshida, Shin-Ichi,Yamada, Shin-Ichi,Shimizu, Toshiaki
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p. 6102 - 6110
(2007/10/03)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF BIOTIN
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The present invention relates to an improved process for the preparation of optically active (+) biotin of formula (I) in pure form.
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- Nutritional supplement
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A nutritional supplement is provided that is designed to provide nutritional benefits as well as to assist the body with detoxification. By providing a supplement that serves both of these functions, the present invention may enable persons to improve their overall wellness.
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- Nucleic acid labeling compounds
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Nucleic acid labeling compounds containing heterocyclic derivatives are disclosed. The heterocyclic derivative containing compounds are synthesized by condensing a heterocyclic derivative with a cyclic group (e.g. a ribofuranose derivative). The labeling compounds are suitable for enzymatic attachment to a nucleic acid, either terminally or internally, to provide a mechanism of nucleic acid detection.
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- Total synthesis of D-(+)-biotin
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The total synthesis of D-(+)-biotin has been described starting from D-(+)-glucosamine using acyliminium chemisty. A total synthesis of D-(+)-biotin is described starting from D-(+)-glucosamine using acyliminium chemistry.
- Chavan, Subhash P.,Ramakrishna, Guduru,Gonnade, Rajesh G.,Bhadbhade, Mohan M.
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p. 7307 - 7310
(2007/10/03)
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- INTERMEDIATE FOR BIOTIN AND PROCESS FOR PRODUCING THE SAME
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The present invention is to provide a process for preparing a synthetic intermediate of biotin which is industrially advantageous, and discloses a process for preparing a compound represented by the formula (I) : ???wherein R1 and R2 may be the same or different from each other, and each represents hydrogen atom, a benzyl group which may have a substituent(s) on the benzene ring, a benzhydryl group which may have a substituent(s) on the benzen ring, or a trityl group which may have a substituent(s) on the benzene ring, R3 represents cyano group, carboxyl group, an alkoxycarbonyl group, an alkylthiocarbonyl group, or a carbamoyl group which may have a substituent, or a salt thereof which comprises subjecting a compound represented by the formula (II-a) : ???wherein the symbols have the same meanings as defined above, or a salt thereof to ring transformation.
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- Phototriggered drug release from functionalized oligonucleotides by a molecular beacon strategy
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More than just a light switch: A phototriggered molecule-releasing system controlled through intramolecular triplet quenching by using a molecular beacon strategy with photoactive probe oligodeoxynucleotides (ODNs) has been developed (see picture).
- Okamato, Akimitsu,Tanabe, Kazuhito,Inasaki, Takaheshi,Saito, Isao
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p. 2502 - 2504
(2007/10/03)
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- Synthetic Studies on d-Biotin, Part 6:1 An Expeditious and Enantiocontrolled Approach to the Total Synthesis of d-Biotin via a Polymer-Supported Chiral Oxazaborolidine-Catalyzed Reduction of meso-Cyclic Imide Strategy
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An efficient and highly enantioselective synthesis of d-biotin from the known cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid (5) was accomplished in 48% overall yield. The key reactions in the sequence involve the catalytic enantioselective reduction of meso-cyclic imide 6 using polymer-supported chiral oxazoborolidine, derived from (S)-α,α -diphenylprolinol and polymer-bound sulfonyl chloride, and the installation of the C5 side chain at C4 in the thiolactone 9 via a Ni/C-catalyzed Fukuyama coupling reaction.
- Chen, Fen-Er,Yuan, Jian-Li,Dai, Hui-Fang,Kuang, Yun-Yan,Chu, Yong
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p. 2155 - 2160
(2007/10/03)
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- Hypophosphorous acid-iodine: An efficient and mild reagent for cleavage of N-C bond
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A mixture of hypophosphorous acid (H3PO2) and iodine in acetic acid can selectively cleave the N-alkyl bond in a variety of substituted heterocylic compounds in good to excellent yields without any damage to amide bond present in the substrates.
- Meng, Ge,He, Yan-Ping,Chen, Fen-Er
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p. 2593 - 2598
(2007/10/03)
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- Synthetic studies on d-biotin. Part 7: A practical asymmetric total synthesis of d-biotin via enantioselective reduction of meso-cyclic imide catalyzed by oxazborolidine
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A novel and convenient method for the stereoselective synthesis of d-biotin 1 starting from the commercially available cis-1,3-dibenzyl-2- imidazolidone-4,5-dicarboxylic acid 2 has been developed. The key features of this synthesis include the enantioselective reduction of a meso-cyclic imide, mediated by a chiral oxazborolidine catalyst, derived from (1S,2S)-(+)-threo-1- (4-nitrophenyl)-2-amino-1,3-propanediol and the direct introduction of a C 5 side chain to the (3aS,6aR)-thiolactone through a modified di-Grignard reaction. Enantioselectivities of 98% in the oxazborolidine- catalyzed asymmetric reduction process have been achieved.
- Chen, Fen-Er,Dai, Hui-Fang,Kuang, Yun-Yan,Jia, Hui-Qing
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p. 3667 - 3672
(2007/10/03)
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- 2-Thiazolidinone: A novel thiol protective surrogate of complete atom efficiency, a practical synthesis of (+)-biotin
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2-Thiazolidinone derivatives were shown to be novel protective surrogates of a thiol group in L-cysteine derivatives. After elaboration at the C-4 substituent, the thiol group was completely liberated by simple heating in DMF whose atom efficiency is 100%. A practical synthesis of (+)-biotin was accomplished by the use of the strategy employing 4-functionalized 2-thiazolidinone derivatives as the intermediates, allowing a synthesis of (+)-biotin in 10 steps and in 31% overall yield. Short steps, high yield, and ease of operation of the present approach would permit the hitherto most efficient access to (+)-biotin.
- Seki, Masahiko,Kimura, Mayumi,Hatsuda, Masanori,Yoshida, Shin-Ichi,Shimizu, Toshiaki
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p. 8905 - 8907
(2007/10/03)
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