- Structures of products of the reactions of halotriorganosilanes with triethyl phosphite and with sodium dialkyl phosphites
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1. The reaction of bromotriethylsilane with triethyl phosphite at high temperatures (155-180°) goes with formation mainly of silyl-substituted tervalent phosphorus derivatives, which readily combine with sulfur and undergo Arbuzov reaction with ethyl bromide. 2. In the reactions of trialkylhalosilanes with sodium diethyl phosphite the products are not quinquevalent phosphorus compounds containing the Si-P bond as was supposed earlier, but the isomeric tervalent phosphorus compounds containing the Si-O-P link. 3. The thione-thiol isomerization of Si-P was effected in presence of ethyl bromide.
- Bugerenko,Chernyshev,Popov
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- Efficient synthesis of the four diastereomers of phosphothreonine from lactaldehyde
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The four stereoisomers of phosphothreonine are obtained in high diastereomeric purity based on the stereoselective addition of trimethylsilyldiethylphosphite (TMSDEP) to scalemic N-trimethylsilyl-lacticimine and addition of TMSDEP to lactaldehyde followed by Mitsunobu inversion of the corresponding α-hydroxy-β-silyloxy phosphonate.
- Bongini, Alessandro,Camerini, Roberto,Panunzio, Mauro
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- A new selenium-transferring reagent - Triphenylphosphine selenide
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Triphenylphosphine selenide and its polymer-supported counterpart are found to be efficient selenium-transferring reagents for the conversion of H-phosphonate diesters and phosphite triesters into the corresponding phosphoroselenoate derivatives.
- Bollmark,Stawinski
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- 2-Pyridylphosphonates: A new type of modification for nucleotide analogues
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Suitably protected dithymidine H-phosphonates afforded the corresponding dinucleoside 2-pyridylphosphonates upon treatment with N-methoxypyridinium tosylate in acetonitrile in the presence of 1,8-diazabicylo[5.4.0]undec-7-ene (DBU). The reaction was rapid (ca. 5 min), practically quantitative and proceeded stereospecifically, most likely with retention of configuration at the phosphorus centre.
- Johansson, Tommy,Kers, Annika,Stawinski, Jacek
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- New Synthesis of Diethyl Trimethylsilyl Phosphite
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Diethyl phosphonate rapidly reacted with hexamethyldisilazane at 20°C in the presence of 52 mol % of zinc(II) chloride to give 76% of diethyl trimethylsilyl phosphite.
- Morgalyuk,Strelkova,Buyanovskaya,Brel
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- Synthesis of Rovafovir Etalafenamide (Part III): Evolution of the Synthetic Process to the Phosphonamidate Fragment
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Phosphonamidate 1 is a key fragment in the assembly of rovafovir etalafenamide, a novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for the treatment of HIV infection. An early manufacturing route, relying on simulated moving bed (SMB) chromatography for the separation of phosphorus diastereomers, was executed on scale to produce multiple batches of 1. However, developing alternative synthetic conditions became desirable in consideration of the high production cost, long lead time, and high process mass intensity (PMI) associated with SMB. Several strategies to improve these factors are described herein, including epimerization and recycling of the undesired (R)-phosphorus diastereomer, design of stereoselective approaches to establish the desired (S)-configuration at phosphorus, and identification of conditions or derivatives to allow for selective crystallization. Ultimately, a second-generation route to 1 was developed and demonstrated on scale. The new route achieves the separation of phosphorus diastereomers by means of selective crystallization, does not require SMB, and offers lower PMI, cost, and lead time.
- Ambrosi, Andrea,Bringley, Dustin A.,Calimsiz, Selcuk,Curl, Jonah,Garber, Jeffrey A. O.,Huynh, Huy,Kwong, Bernard,Lapina, Olga,Leung, Edmund,Lin, Lennie,Martins, Andrew,McGinitie, Teague,Mohan, Sankar,Phull, Jaspal,Roberts, Ben,Rosario, Mary,Sarma, Keshab,Shen, Jinyu,Shi, Bing,Standley, Eric A.,Wang, Li,Wang, Xueqing,Yu, Guojun
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supporting information
p. 1247 - 1262
(2021/05/29)
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- Chlorosilane-Catalyzed Coupling of Hydrogen Phosphine Oxides with Acyl Chlorides Generating Acylphosphine Oxides
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We report a new method for the synthesis of acylphosphine oxides by the direct coupling of hydrogen phosphine oxides and acyl chlorides mediated by chlorosilanes. This new protocol is greener and safer, because it precludes the generation of volatile haloalkanes and the use of oxidants employed in the conventional methods. Moreover, moisture-unstable acylphosphine oxides that are difficult to prepare via the conventional methods can be generated using this new method.
- Zhang, Jian-Qiu,Han, Li-Biao
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supporting information
p. 4633 - 4637
(2020/06/23)
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- New synthesis of trimethylsilyl esters of phosphorus(III) acids
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Abstract: A novel synthetically important reaction has been developed for the quick, convenient, and high-yield preparation of trimethylsilyl esters of phosphorus(III) acids, synthetically valuable Michaelis–Arbuzov reaction precursors. Commercially and synthetically available initial compounds used are derivatives of propan-2-ol phosphorylated in the second position capable of long-term storage and available silylating reagents: hexamethyldisilazane, bis(trimethylsilyl)acetamide, and diethyl(trimethylsilyl)amine. Also, a stepwise reaction scheme of the starting compounds with silylating reagents has been proposed. Graphic abstract: [Figure not available: see fulltext.].
- Morgalyuk, Vasily,Strelkova, Tatyana,Brel, Valery
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p. 1993 - 1997
(2019/11/13)
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- Steric Enforcement of cis-Epoxide Formation in the Radical C-O-Coupling Reaction by Which (S)-2-Hydroxypropylphosphonate Epoxidase (HppE) Produces Fosfomycin
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(S)-2-Hydroxypropylphosphonate [(S)-2-HPP, 1] epoxidase (HppE) reduces H2O2 at its nonheme-iron cofactor to install the oxirane "warhead" of the antibiotic fosfomycin. The net replacement of the C1 pro-R hydrogen of 1 by its C2 oxygen, with inversion of configuration at C1, yields the cis-epoxide of the drug [(1R,2S)-epoxypropylphosphonic acid (cis-Fos, 2)]. Here we show that HppE achieves ~95% selectivity for C1 inversion and cis-epoxide formation via steric guidance of a radical-coupling mechanism. Published structures of the HppE·FeII·1 and HppE·ZnII·2 complexes reveal distinct pockets for C3 of the substrate and product and identify four hydrophobic residues - Leu120, Leu144, Phe182, and Leu193 - close to C3 in one of the complexes. Replacement of Leu193 in the substrate C3 pocket with the bulkier Phe enhances stereoselectivity (cis:trans ~99:1), whereas the Leu120Phe substitution in the product C3 pocket diminishes it (~82:18). Retention of C1 configuration and trans-epoxide formation become predominant with the bulk-reducing Phe182Ala substitution in the substrate C3 pocket (~13:87), trifluorination of C3 (~23:77), or both (~1:99). The effect of C3 trifluorination is counteracted by the more constrained substrate C3 pockets in the Leu193Phe (~56:44) and Leu144Phe/Leu193Phe (~90:10) variants. The ability of HppE to epoxidize substrate analogues bearing halogens at C3, C1, or both is inconsistent with a published hypothesis of polar cyclization via a C1 carbocation. Rather, specific enzyme-substrate contacts drive inversion of the C1 radical - as proposed in a recent computational study - to direct formation of the more potently antibacterial cis-epoxide by radicaloid C-O coupling.
- Zhou, Shengbin,Pan, Juan,Davis, Katherine M.,Schaperdoth, Irene,Wang, Bo,Boal, Amie K.,Krebs, Carsten,Bollinger, J. Martin
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supporting information
p. 20397 - 20406
(2019/12/27)
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- On the sulfurization of h-phosphonate diesters and phosphite triesters using elemental sulfur
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Sulfurization of tetracoordinate and tricoordinate P(III) derivatives, namely, H-phosphonate diesters, H-phosphonothioate diesters, and phosphite triesters with elemental sulfur under various experimental conditions, was investigated.
- Wallin, Richard,Kalek, Marcin,Bartoszewicz, Agnieszka,Thelin, Mats,Stawinski, Jacek
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scheme or table
p. 908 - 916
(2009/12/07)
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- Application of silicon-phosphorus based reagents in synthesis of aminophosphonates. Part 2: Reactions of N-(Triphenylmethyl)-aldimines with the silylated phosphorus acid esters
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Reactions of silylated phosphorus acid esters with N-triphenylmethylaldimines (N-tritylaldimines) were investigated. N-Tritylmethaneimine reacts at room temperature with a mixture of P(OMe)3 and Me3SiBr forming the corresponding aminophosphonate derivatives in high yield. Other N-tritylimines are resistant toward the silylated reagents at room temperature, but undergo a similar phosphorylation reaction at elevated temperatures to form the expected aminophosphonic acids.
- Boduszek,Soroka
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p. 1105 - 1111
(2007/10/03)
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- A general strategy for the practical synthesis of nojirimycin C-glycosides and analogues. Extension to the first reported example of an iminosugar 1-phosphonate
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An efficient and versatile strategy for the synthesis of nojirimycin C-glycosides and related compounds with full stereocontrol is reported. The key steps of the process are the addition of organometallic reagents onto an L-sorbose-derived imine (13) followed by an internal reductive amination. The addition step, which controls the α vs β-configuration at the pseudoanomeric center in the final product, is highly diastereoselective (re-face addition), and the stereoselectivity can be effectively inverted by adding an external monodentate Lewis acid (si-face addition). The complete synthesis could be achieved in 10 steps only from commercially available 2,3;4,6-di-O-isopropylidene-C-L-sorbofuranose and provided α or β-1-C-substituted 1-deoxynojirimycin derivatives in 27-52% overall yield. The strategy was successfully extended to the first example of an iminosugar 1-phosphonate. The methodology provides access to a wide range of biologically relevant glycoconjugate mimetics in which the glycosidic function is replaced by an imino-C-glycosidic linkage.
- Godin, Guillaume,Compain, Philippe,Masson, Geraldine,Martin, Olivier R.
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p. 6960 - 6970
(2007/10/03)
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- Application of bromotrimethylsilane and trialkyl phosphites for convenient and effective synthesis of aminophosphonic acids and corresponding monoalkyl and dialkyl esters
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Application of bromotrimethylsilane (Br-TMS) in a mixture with trialkyl phosphite for synthesis of various aminophosphonic acids and esters was investigated. It was found, that appropriate mixtures of Br-TMS and trimethyl phosphite or triethyl phosphite were effective reagents for phosphorylation of various aldimines, obtained from aromatic and heteroaromatic aldehydes. Products of these reactions were corresponding aminophosphonic acids, or corresponding dialkyl or monoalkyl esters, respectively.
- Boduszek
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p. 663 - 672
(2007/10/03)
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- Synthesis and plant growth regulating activity of new triazolo- and pyrazolopyrimidine derivatives of aminomethyl-, aminoalkyloxymethyl dimethylphosphine oxides and (aminomethane)phosphonic acid esters
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New triazolo[4,5-d]pyrimidine and pyrazolo[3,4-d]pyrimidine derivatives of aminomethyl- and aminomethyloxymethyl dimethylphosphine oxides 8-14 as well as of esters of (aminomethane) phosphonic acid 18-20 were synthesized. The structure of the compounds prepared was confirmed by means of elemental analysis, IR, 1H- and 31P{1H}-NMR spectroscopy. Tertiary phosphine oxides 8, 9 and 12 as well as phosphonate 20 showed herbicidal and plant growth regulating activity.
- Stanoeva, Elena,Varbanov, Sabi,Alexieva, Vera,Sergiev, Iskren,Vasileva, Vesselina,Rashkova, Marieta,Georgieva, Angelina
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p. 117 - 133
(2007/10/03)
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- SUBSTITUTED CYCLOALKANECARBOXYLIC ACID DERIVATIVES AS MATRIX METALLOPROTEASE INHIBITORS
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Inhibitors for matrix metalloproteases, pharmaceutical compositions containing them, and a process for using them to treat a variety of physiological conditions. The compounds of the invention have the generalized formula STR1 wherein each T is a substituent g roup; x is 0, 1, or 2; the group D represents STR2 the subscript "e" is 2 or 3; the group R 14 represents a variety of possible substituent groups of the cycloalkyl ring between D and G; the subscript "k" is 0-2; and the group G represents M, STR3 in which M represents--CO 2 H,--CON(R 11) 2, or--CO 2 R 12 ; and R 13 represents any of the side chains of the 19 noncyclic occurring amino acids. "
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- Arylmethylphosphonates and phosphonic acids useful as anti-inflammatory agents
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This invention provides a new use of acids, esters, and salts of arylmethylphosphonates of Formula I, STR1 or phosphonic acid derivatives of Formula II STR2 as anti-inflammatory and anti-arthritic agents. Representative compounds include 4-dodecyloxybenzylphosphonic acid dimethyl ester, (2-naphthalenylmethyl)phosphonic acid dimethyl ester, and ([1,1 '-biphenyl]-2-ylmethyl)phosphonic acid dimethyl ester. The invention also provides novel acids, esters, and salts of arylmethylphosphonic acid, phosphonic acid and derivatives.
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- A FACILE SYNTHESIS OF TRIALKYLSILYLPHOSPHITES AND PHOSPHATES
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Trialkylsilylphosphites (1a-1d) and trialkylsilylphosphates (2a-2d) were synthesized in good yield by a facile method.The method could be easily used to prepare P-O-Si bond and P-Si bond compounds from dialkylphosphites and trialkylchlorosilanes.Key words: Phosphates; trialkylsilylphosphites; trialkylchlorosilanes.
- Li, Zhonghua,Zhu, Chuanfang,Zhao, Yongzhen
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p. 229 - 232
(2007/10/02)
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- REACTIONS OF 2-AMINO-4,5-BENZO-1,3,2-DIOXAPHOSPHOLANE WITH CARBOXYLIC AND PHOSPHOROUS ACIDS AND ACETIC ANHYDRIDE
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The reactions of 2-amino-4,5-benzo-1,3,2-dioxaphospholane with acetic acid, benzoic acid, and acetic anhydride yield 2-trimethylsiloxy-4,5-benzo-1,3,2-dioxaphospholane.Upon reaction with dialkyl phosphites, the silylamidophosphite acts as a silylating agent.
- Pudovik, M. A.,Kibardina, L. K.,Pudovik, A. N.
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p. 214 - 216
(2007/10/02)
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- Mesylate Derivatives of α-Hydroxy Phosphonates. Formation of Carbocations Adjacent to the Diethyl Phosphonate Group
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Mesylates 3-6 have been prepared and reacted in a variety of solvents.Product, rate, and solvent effect studies implicate carbocationic intermediates in these solvolyses despite the electron-withdrawing PO(OEt)2 group.Mesylate 3 gave exclusive substitution products.Optically active 3 gave racemic products on trifluoroacetolysis. α-Deuterium isotope effects were also in line with a cationic intermediate.Mesylate 4 gave some elimination product, 27, along with the substitution product 28, also via a cationic intermediate.Mesylates 5 and 6 gave exclusive elimination products.A β-deuterium isotope effect study gave a kH6/kD6 value of 2.8.This isotope effect, along with a small m value (0.45), suggested the intermediacy of a reversibly formed ion pair which subsequently loses a proton.This mechanism represents the merging of the classical E1 mechanism and the E2C(+) mechanism, the latter representing the cationic counterpart of the E1cb mechanism.Analysis of the solvolysis rates of 3 and 4 led to the conclusion that cationic intermediates are formed quite easily.Reasons are suggested for this unexpectedly facile generation of cations adjacent to the potent electron-withdrawing PO(OEt)2 substituent.
- Creary, Xavier,Geiger, Cristina C.,Hilton, Kathryn
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p. 2851 - 2858
(2007/10/02)
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- Silyl Phosphites. 15. Reactions of Silyl Phosphites with α-Halo Carbonyl Compounds. Elucidation of the Mechanism of the Perkow Reaction and Related Reactions with Confirmed Experiments
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The reactions of silyl phosphites, i.e., tris(trimethylsilyl)phosphite (1), diethyl trimethylsilyl phosphite (11), and bis(trimethylsilyl) ethyl phosphite (12), with a variety of α-halo carbonyl compounds gave the 1:1 carbonyl addition products (6, 13, and 14), enol phosphates (5 and 26), and/or 2-oxophosphonates (4 and 25).Substituents on the phosphites and the α-halo carbonyl compounds have influenced the product ratios.The results of these reactions strongly suggest that the Perkow reaction proceeds via an initial attack of phosphite on the carbonyl carbon of the α-halo carbonyl compound.Treatment of bis(trimethylsilyl) 1--2-halo phosphonates (6) with sodium methoxide in methanol followed by retrimethylsilylation gave bis(trimethylsilyl) 1,2-epoxy phosphonates (17), bis(trimethylsilyl) 2-oxo phosphonates (4), and bis(trimethylsilyl) methyl phosphate (21).On the other hand, diethyl 1-hydroxy-2-halo phosphonates (22) were converted by treatment with different bases to 1,2-epoxy phosphonates (23) predominantly in good yields.When some of tri-n-butyltin alkoxides were used as bases, enol phosphates (26) were obtained selectively.Several bis(trimethylsilyl) esters obtained in the above reactions were successfully converted to the corresponding monoanilinium salts in high yields by treatment with aniline-containing alcohols.
- Sekine, Mitsuo,Okimoto, Kiyomi,Yamada, Khoji,Hata, Tsujiaki
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p. 2097 - 2107
(2007/10/02)
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- Silyl Phosphites. 16. Mechanism of the Perkow Reaction and the Kukhtin-Ramirez Reaction. Elucidation by means of a New Type of Phosphoryl Rearrangements Utilizing Silyl Phosphites
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Reactions of α-lithiated diethyl α-benzylphosphonate (4) with benzoyl chloride and chloroiodomethane afforded benzoylated and chloromethylated products (1 and 2) corresponding to the 1:1 carbonyl adducts of diethyl trimethylsilyl phosphite with benzil and phenacyl chloride which were not obtained by the reactions between the phosphite and benzil or phenacyl chloride.Pyrolysis of 1 and 2 afforded 1,3,2-dioxaphosphole (6) and enol phosphate (8).On the other hand, treatment of 1 and 2 with tetrabutylammonium fluoride afforded benzoin phosphate (7)and 1,2-epoxy phosphonate (14), respectively, as the main products.These results are also discussed in connection with the mechanism of the Perkow reaction and the Kukhtin-Ramirez reaction.
- Sekine, Mitsuo,Nakajima, Masashi,Hata, Tsujiaki
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p. 4030 - 4034
(2007/10/02)
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- Novel Synthetic Aspects of the Phosphonate-Phosphate-Rearrangement. II. Synthesis of Enolphosphates from 1-Oxoalkanphosphonates and Sulfur-Ylides
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Acylphosphonates 1 react with Sulfur-ylides 2 to give enolphosphates 3 and phosphonophosphates 4.The product ratio of 3 and 4 is determined by the substituent R3.If R3 is not electronwithdrawing the phosphonophosphate 4 is the sole reaction product. - Keywords: Acylphosphonates, behaviour towards S-ylides; Rearrangement of α-hydroxyphosphonates
- Hammerschmidt, Friedrich,Zbiral, Erich
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p. 1015 - 1024
(2007/10/02)
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