- Synthesis of novel deoxy λ5 phospha sugar nucleosides: 1,3-dipolar cycloaddition of an azidophospholane with alkynes
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Several novel phospha sugar nucleosides, analogs of normal sugar nucleosides, were synthesized from a phospholene 1-oxide derivative. Bromination of a phospholene precursor in aqueous organic medium gave regio diastereomers, the threo and erythro bromohydrins 3 (1-bromo-1,3,4-trideoxy-1,4-C-[(R,S)-phenylphosphinylidene]-glycero- tetrofuranose). Further substitution of the threo isomer 3a with sodium azide led to its corresponding azidophospholane 4 (1-azido-1,3,4-trideoxy-2-methyl-1,4-C-[(R)-phenylphosphinylidene]-β-D- glycero-tetrofuranose). 1,3-Dipolar cycloaddition of 4 with various electron-deficient and electron-rich alkynes afforded triazole derivatives that are nucleoside analogues. The strong electron-withdrawing phosphoryl group in the hemiacetal ring exerted no effect over reaction regioselectivity of the 1,3-dipolar cycloaddition, but steric effects of the alkynes played a vital role on the selectivity, since the regioisomer ratios and the rates and yields of cycloadducts changed as the bulkiness of the substituents on the acetylene changes. Structures of all compounds were unequivocally confirmed by 1H, 13C, and 31P NMR and mass spectral studies. Single crystal X-ray crystallographic analysis of some derivatives allowed determination of configuration of the phospha sugar nucleosides.
- Yamashita, Mitsuji,Mallikarjuna Reddy, Putta,Kato, Yukihiro,Krishna Reddy, Valluru,Suzuki, Kazumitsu,Oshikawa, Tatsuo
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- Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides
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A series of 1-substituted-3-methyl-2-phospholene oxides was prepared from the corresponding 3-phospholene oxides by double bond rearrangement. The 2-phospholene oxides could be obtained by heating the 3-phospholene oxides in methanesulfonic acid, or via the formation of cyclic chlorophosphonium salts. Whereas mixtures of the 2- and 3-phospholene oxides formed, when the isomerization of 3-phospholene oxides was attempted under thermal conditions, or in the presence of a base. The mechanisms of the various double bond migration pathways were elucidated by quantum chemical calculations.
- Bagi, Péter,Herbay, Réka,Keglevich, Gy?rgy,Mucsi, Zoltán,Péczka, Nikolett,Timári, István
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supporting information
p. 818 - 832
(2020/05/14)
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- Isomerization and application of phospholene oxides
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In this research, an investigation of the isomerization and the applications of 3-phospholene oxides were elaborated. The isomerization of 3-phospholene oxides to 2-phospholene oxides was investigated under thermal condition. The application of bases and acids was also tested in this reaction. Moreover, the isomerization was also elaborated via the formation of halophosphonium salt intermediates. The 3-phospholene oxides were deoxygenated and transformed to the corresponding palladium complexes.
- Herbay, Réka,Péczka, Nikolett,Gy?rke, Gábor,Bagi, Péter,Fogassy, Elemér,Keglevich, Gy?rgy
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p. 610 - 613
(2019/01/05)
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- METHOD FOR PRODUCING 3-METHYL-1-PHENYLPHOSPHOLENE OXIDE
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PROBLEM TO BE SOLVED: To provide a method for producing 3-methyl-1-phenylphospholene oxide capable of improving productivity of 3-methyl-1-phenylphospholene oxide while being a simple method. SOLUTION: There is provided a method for producing 3-methyl-1-phenylphospholene which comprises: preparing a reaction liquid containing an adduct of dichlorophenylphosphine by reacting dichlorophenylphosphine and isoprene in an aromatic hydrocarbon-based solvent; preparing a hydrolysis liquid containing 3-methyl-1-phenylphospholene oxide by hydrolyzing the adduct of dichlorophenylphosphine by adding water to the reaction liquid without separating the adduct of dichlorophenylphosphine from the reaction liquid; and extracting 3-methyl-1-phenylphospholene oxide from the hydrolysis liquid using an aromatic hydrocarbon-based solvent as an extraction solvent. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPO&INPIT
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Paragraph 0089-0101
(2019/08/14)
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- A novel preparation of chlorophospholenium chlorides and their application in the synthesis of phospholene boranes
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A novel preparation of 1-chloro-3-methyl-3-phospholenium chlorides was developed by reacting 1-substituted-3-methyl-3-phospholene 1-oxides with oxalyl chloride. The obtained cyclic chlorophosphonium salts were reacted with LiBH4to afford the corresponding 1-substituted-3-methyl-3-phospholene boranes. The latter protocol involves a silane-free deoxygenation, and borane complex formation. In one instance, a 2-phospholene borane and the corresponding P-oxide were synthesized via rearrangement of the double bond in the cyclic chlorophosphonium salt. This double bond migration was investigated by quantum chemical calculations.
- Herbay, Réka,Bagi, Péter,Mucsi, Zoltán,Mátrav?lgyi, Béla,Drahos, László,Fogassy, Elemér,Keglevich, Gy?rgy
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p. 458 - 461
(2017/01/11)
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- 3-methyl-1-phenyl-1-phosphorus heterocycle penta-3-ene-1-oxide
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The invention discloses a synthesis method of 3-methyl-1-phenyl-1-phosphacyclopenta-3-ene-1-oxide. The synthesis method comprises the following steps: 1) putting dichlorophenyl phosphine, isoprene and an oxidant 2246 in an organic solvent to react at 60-70 DEG C to obtain a white crystal, and purifying the crystal; 2) dissolving the product obtained after washing and purifying in ice water, fully hydrolyzing the product to obtain hydrolysate, then adjusting the pH value of the hydrolysate to be 6-7, then adding sodium chloride to prepare the hydrolysate into a saturated solution of sodium chloride, then fully extracting the saturated solution with an organic extraction agent to obtain organic extract, removing the moisture in the organic extract, and then removing the organic extraction agent and other volatile matters in the organic extract, thus obtaining a liquid mixture; 3) distilling the liquid mixture obtained in the former step at reduced pressure, and collecting the fraction, thus obtaining the target product. The synthesis method has the beneficial effects of relatively high product yield and reaction efficiency.
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Paragraph 0034; 0059-0063
(2017/01/05)
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- Novel Multiple Type Molecular Targeted Antitumor Agents: Preparation and Preclinical Evaluation of Low-Molecular-Weight Phospha Sugar Derivatives
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Phospha sugar derivatives of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide and 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide were synthesized from 2-phospholenes and evaluated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide method against leukemia cell lines, and then characterized by cell cycle analysis, Western blot analysis, and molecular docking simulation. Phospha sugar derivatives were revealed to be potential antitumor agents against leukemia cell lines such as U937 and K562. Cell cycle analysis indicated that phospha sugar derivatives induced apoptoses. Western blot analyses against U937 showed that phospha sugar derivatives regulate many mitotic regulators in cell cycle. Results of molecular docking simulation suggested that phospha sugar derivatives enter the pockets present in cell cycle and apoptosis-related proteins.
- Makita, Reiko,Yamashita, Mitsuji,Yamaoka, Mayumi,Fujie, Michio,Nakamura, Satoki,Oshikawa, Tatsuo,Yamashita, Junko,Yamada, Manabu,Asai, Kazuhide,Suyama, Takuya,Kondo, Mitsuru,Hasegawa, Hiroko,Okita, Yoshimitsu,Hirakawa, Kazutaka,Toda, Mitsuo,Ohnishi, Kazunori,Sugimura, Haruhiko
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p. 733 - 740
(2016/01/15)
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- METHOD OF PRODUCING PHOSPHOLENE OXIDE
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A method of producing a phospholene oxide is disclosed. A dihalohydrocarbylphosphine, 2-methyl-l,3-butadiene, and a halogenated hydrocarbon solvent are combined to form an adduct via an addition reaction in a homogenous system wherein the ratio of the 2-methyl- 1,3 -butadiene to the dihalohydrocarbylphosphine is from 1.0 to 2.0 and wherein the solvent is present in an amount of greater than 200 mL per mole of dihalohydrocarbylphosphine. The adduct is combined with alcohol and a carbonate or with a solution of metal hydroxide and water to form the phospholene oxide.
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Paragraph 0021; 0046; 0047; 0048; 0049, 0050
(2014/10/18)
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- Synthesis of Some 1-aryl-2,3-dibromophospholanes as novel anti-cancer agents
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Novel phosphorus heterocyclic compounds, 3-methyl-1-(3-bromophenyl as well as some 3-substituted phenyl)-2- phospholene 1-oxides (1d as well as 1b, 1c, and 1f), were synthesized from 1-phenyl-2-phospholene 1-oxide 1a via 3-methyl-1-(3-nitrophenyl)-2-phospholene 1-oxide (1b). 1-(4-Bromophenyl)-2- phospholene 1e was prepared by Grignard coupling reaction of 1-chloro-3-methyl-2-phospholene 1-oxide with 4-bromophenylmagnesium bromide. 2,3-Dibromo-3-methyl-1-arylphospholane 1-oxides (2a-2e) were prepared by the addition reaction of bromine to the C=C double bond of 2-phospholenes 1a-1e. The substituent effect of the phenyl group of the 1-aryl-phospho lanes 2 on the observed anti-proliferative effect against U937 leukemia cell lines evaluated by MTT in vitro methods showed that 2,3-dibromo-3-methyl-1-(4-bromophenyl) phospholane (2e) was the most active among 2. These novel dibromophosphorus heterocyclic derivatives exhibit much higher anti-cancer activity than Gleevec (molecular targeting chemotherapeutic agent) against U937 cells.
- Yamada, Manabu,Asai, Kazuhide,Yamashita, Junko,Suyama, Takuya,Niimi, Taishi,Maddali, Kasthuraiah,Fujie, Michio,Nakamura, Satoki,Kimura, Motohiko,Tanaka, Yasutaka,Toda, Mitsuo,Yamashita, Mitsuji
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p. 173 - 180
(2011/06/24)
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- Research and development of phospha sugar anti-cancer agents with anti-leukemic activity
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We have synthesized three deoxybromophospha sugar analogues, 4-bromo-3-methyl-l-phenyl-2-phospholene 1-oxide (MBMPP (2)), 2,3-dibromo-3-methyl-l-phenylphospholane 1-oxide (DBMPP (3)), and 2,3,4-tribromo-3-methyl-1-phenylphospholane 1-oxide (TBMPP (4)), by the reaction of 3-methyl-l-phenyl-2-phospholene 1-oxide (lb) and/or 2 with bromine, and investigated their potentials as anti-leukemic agents against human leukemia cell lines of K562 and U937. Cells' growth inhibition was determined by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) in vitro assay. All agents showed inhibitory effects on leukemia cell proliferation, indicating that inhibition appeared to be dependent on number of bromine substituent in the heterocyclic structure. Further, the phospha sugar derivatives did not show any inhibitory effects on normal cell proliferation. These agents may facilitate the development of new strategies in molecular targeting anti-leukemic therapy.
- Yamashita, Junko,Suyamab, Takuya,Asai, Kazuhide,Yamada, Manabu,Niimi, Taishi,Fujie, Michio,Nakamura, Satoki,Ohnishi, Kazunori,Yamashita, Mitsuji
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scheme or table
p. 89 - 97
(2011/06/24)
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- Preparation and characterization of novel 4-bromo-3,4-dimethyl-1-phenyl-2- phospholene 1-oxide and the analogous phosphorus heterocycles or phospha sugars
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4-Bromo-3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (3c) was first synthesized from 3,4-dimethyl-1-phenyl-2-phospholene 1-oxide (2c) by a bromo-radical substitution reaction occurred at C-4 position by N-bromosuccinimide and 2,2′-azobisisobutyronitrile. The novel phospha sugar analogue 3c exerted high anti-proliferative effect on U937 cells evaluated by MTT in vitro methods and was much more efficient than that of Gleevec, which is known as a molecule targeting chemotherapeutical agent. The substitution of 2-phospholenes at C-3 and C-4 position with methyl groups as well as 4-bromo substituent suggests a good anti-proliferative effect.
- Yamada, Manabu,Yamashita, Mitsuji,Suyama, Takuya,Yamashita, Junko,Asai, Kazuhide,Niimi, Taishi,Ozaki, Nobuhisa,Fujie, Michio,Maddali, Kasthuraiah,Nakamura, Satoki,Ohnishi, Kazunori
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experimental part
p. 5943 - 5946
(2010/11/18)
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- Synthesis and characterization of the novel 1-(substituted phenoxy/phenyl)-2-phospholene and phospholane 1-oxide derivatives
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The synthesis of the novel 1-(substituted phenoxy/phenyl)-2-phospholene and phospholane 1-oxide derivatives, which are analogs of sugars having a phosphorus atom in place of the ring oxygen of normal sugars, is described. All of the synthesized derivatives are structurally characterized by multi nuclear NMR, mass, and IR spectral data, elemental and X-ray crystallographic analyses.
- Reddy, Valluru Krishna,Onogawa, Jun-Ichi,Rao, Lakonda Nagaprasada,Oshikawa, Tatsuo,Takahashi, Masaki,Yamashita, Mitsuji
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- Synthesis of novel 1-(substituted phenyl)-2-phospholene 1-oxide derivatives
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Several novel 1-(substituted phenyl)-2-phospholene 1-oxide derivatives, which are analogs of sugars having a phosphorus atom in place of the ring oxygen of normal sugars, were synthesized from the corresponding 2-phospholenes as the starting materials. Structures of all the synthesized compounds were unequivocally confirmed by IR, 1H, 13C, and 31P NMR spectral, elemental, and X-ray crystallographic analyses.
- Reddy, Valluru Krishna,Rao, Lakonda Nagaprasada,Oshikawa, Tatsuo,Takahashi, Masaki,Yamashita, Mitsuji
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p. 1801 - 1806
(2007/10/03)
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- Phospho Sugars; Novel Preparation and Their Glycosyl Compounds
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Treatment of 1-phenyl-2-, and -3-phospholene 1-oxides with N-bromosuccinimide affords 4-bromo-1-phenyl-2-phospholene 1-oxide.Substitution of the bromide with acetate, followed by stereoselective oxidation with osmium tetroxide and peracetylation with acetic anhydride/pyridine affords phospho sugar derivatives of tetrafuranose.Furthermore, N-, O-, and S-glycosyl compounds of phospho sugars can be prepared from 3-methyl-1-phenyl-2-phospholene 1-oxide by bromination and nucleophilic substitution reactions.This is a novel and excellent route to prepare phospho sugar derivatives.
- Ikai, Koichi,Iida, Akihito,Yamashita, Mitsuji
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p. 595 - 597
(2007/10/02)
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- REACTION OF PHOSPHOLES WITH ACIDS; PROTON SHIFTS IN 1H-λ5-PHOSPHOLES
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Addition to phospholes of gaseous HCl at -90 deg C or of an excess of trifluoromethanesulphonic acid at -70 deg C, results in P-protonation.The triflate solutions are stable up to room temperature, but the 1H-phospholium chlorides form PV adducts at -70 deg C, which rapidly rearrange by a sigmatropic H-shift.The observed product is a 1-chloro-2,5-dihydrophospholium chloride.Addition of a chloride ion source to the triflates produces the same result.Unprotonated 3,4-dimethyl-1-phenyl phosphole was found to react at a double bond of its 1H-phospholium ion, forming a crystalline 1,3'-biphospholium dimer.
- Quin, Louis D.,Belmont, Stephen E.,Mathey, Francois,Charrier, Claude
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p. 629 - 634
(2007/10/02)
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- Production of cyclic five-membered ring unsaturated phosphine dichlorides
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In the production of isomeric five-membered ring cyclic unsaturated phosphine dichlorides by reacting an organophosphorus dichloride with a diene, the improvement which comprises carrying out the reaction in a carboxylic acid chloride. The product, without isolation, can be directly used in reaction with the carboxylic acid anhydride corresponding to the acid chloride to produce the phosphine oxide, the reaction producing additional acid chloride from the anhydride.
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