- Pteridines. Part CVI. Isolation and characterization of limipterin (1-O-(L-erythro-biopterin-2'-yl)-β-N-acetylglucosamine) and its 5,6,7,8-tetrahydro derivative from green sulfur bacterium Chlorobium limicola f. thiosulfatophilum NCIB 8327
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A new pteridine compound was isolated from green sulfur photosynthetic bacteria, Chlorobium limicola f. thiosulfatophilum NCIB 8327. The structure of this pterin derivative was established to be 1-O-(L-erythro-5,6,7,8-tetrahydropterin-2'-yl)-β-N-acetylglucosamine (1) from 1H-NMR and CD spectra as well as from various mass-spectrometric techniques and chemical-cleavage techniques. Upon acid hydrolysis of 1, equimolar amounts of biopterin (2) and N-acetylglucosamine were produced. The structure of the hydrolysis product 2 was confirmed by comparing its NMR, UV, CD, and MS and its chromatographical behavior with those of an authentic specimen. N-Acetylglucosamine was identified by an enzymatic hydrolysis experiment as well as by NMR and thin layer chromatography. Electrospray (ES), fast-atom-bombardment (FAB), and thermospray (TS) mass spectrometry of 1 yielded an MH+ at m/z 441. Periodate-oxidation experiments of the intact molecule 1 and of its hydrolysis product 2 are consistent with the proposed structure. Differential I2 oxidation experiments with the native compound showed that the in vivo oxidation state of this pterin is its tetrahydro form. We propose the trivial name 'limipterin' for this new compound.
- Cha,Pfleiderer,Yim
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- Photochemistry of dihydrobiopterin in aqueous solution
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Dihydrobiopterin (H2Bip) and its oxidized analogue, biopterin (Bip), accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder in which the protection against UV radiation fails. The photochemistry of H2Bip was studied in neutral aqueous solutions upon UV-A irradiation (320-400 nm) at room temperature. The photochemical reactions were followed by UV/vis spectrophotometry, HPLC and enzymatic methods for hydrogen peroxide (H2O2) determination. Photoproducts were analyzed by means of electrospray ionization mass spectrometry. Under anaerobic conditions, excitation of H2Bip leads to the formation of at least two isomeric dimers with molecular masses equal to exactly twice the molecular mass of the reactant. This reaction takes place from the singlet excited state of the reactant. To the best of our knowledge, this is the first time that the photodimerization of a dihydropterin is reported. In the presence of air, the dimers are again the main photoproducts at the beginning of the reaction, but a small proportion of the reactant is converted into Bip. As the reaction proceeds and enough Bip accumulates in the solution, a photosensitized process starts, where Bip photoinduces the oxidation of H2Bip to Bip, and H 2O2 is formed. As a consequence, the rates of H 2Bip consumption and Bip formation increase as a function of irradiation time, resulting in an autocatalytic photochemical process. In this process, Bip in its triplet excited state reacts with the ground state of H 2Bip. The mechanisms involved are analyzed and the biological implications of the results are discussed. The Royal Society of Chemistry 2010.
- Vignoni, Mariana,Cabrerizo, Franco M.,Lorente, Carolina,Claparols, Catherine,Oliveros, Esther,Thomas, Andres H.
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- Preparation method of L-erythro biopterin compound
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The invention relates to a preparation method of an L-erythro biopterin compound, wherein the L-erythro biopterin compound has a structure as shown in a formula (I), and the L-erythro biopterin compound as shown in the formula (I) is mainly prepared from a compound with a structure as shown in a formula (II) or a formula (III) through a dihydroxylation reaction. The preparation method of the L-erythro biopterin compound is high in production efficiency, low in cost, green, environmentally friendly and suitable for industrial production.
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- Chemical synthesis and purification method of biopterin (by machine translation)
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The method, uses diacetyl biopterin as a raw material, to hydrolyze, with diacetyl biopterin to obtain the salpterin crude, obtained by extracting,hydrogenated,acid after the hydrolysis reaction time is short. and obtaining the methotrexate crude product, according to the method . The method is short in production cycle, cost, and suitable for industrial production. after recrystallization of the mixed solution . The method is simple,efficient, % by weight of the methotrexate aqueous solution obtained by. the method. (by machine translation)
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Paragraph 0011-0012
(2020/03/17)
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- Preparation method of sapropterin dihydrochloride
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The invention relates to a preparation method of sapropterin dihydrochloride shown as formula (I) as shown in the specification. The preparation method comprises the steps of taking 5-deoxy arabinoseas a raw material, performing acetylation reaction in the presence of acetic anhydride to form an intermediate DL-1, allowing DL-1 to react with phenylhydrazine under the catalysis of acetic acid to form an intermediate DL-2, allowing DL-2 and pyrimidylamine sulfate to give a ring closing reaction under the catalysis of anhydrous lithium perchlorate to form an intermediate DL-3, directly oxidizingDL-3 through elemental iodine without purification to form an intermediate DL-4, hydrolyzing DL-4 through potassium hydroxide to form L-biopterin (DL-5), and reducing and salifying L-biopterin through a platinum catalyst to form sapropterin dihydrochloride. The preparation method is easy and simple to operate, high in yield, low in energy consumption and suitable for industrial production, the total yield of the preparation method is greater than 70%, and the purity of a final product reaches above 99.5%.
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Paragraph 0027-0028
(2019/06/07)
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- NOVEL PROCESS FOR THE PREPARATION OF SAPROPTERIN DIHYDROCHLORIDE AND ITS KEY INTERMEDIATE, L-BIOPTERIN
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The present invention relates to a novel process for the preparation of Sapropterin dihydrochloride of formula (1) and its key intermediate L-erythro-biopterin of formula (2). The present process is a simple and economically viable process for commercial production of Sapropterin dihydrochloride of formula (1) and its key intermediate L-biopterin of formula (2).
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Page/Page column 10; 15; 23; 24
(2016/12/22)
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- Crystalline polymorph of biopterin and production method thereof
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Crystalline solids A to E of biopterin are distinguished from each other by diffraction angle in an X-ray powder diffraction pattern measured using Cu—Kα radiation. The crystalline solid A is characterized by strong peak at 4.6° and peaks at 13.6°, 18.1° and 27.5°; the crystalline solid B is characterized by strong peak at 4.85° and peaks at 2.4°, 13.2°, 18.1° and 27.3°; the crystalline solid C is characterized by strong peak at 5.35° and peaks at 10.8°, 21.9° and 27.3°; the crystalline solid D is characterized by strong peak at 5.1° and peaks at 2.6°, 9.2°, 13.4°, 15.4°, 18.3°, 21.8° and 27.3°; and the crystalline solid E is characterized by strong peaks at 4.5° and 5.8°, and peaks at 10.6°, 15.6°, 20.0°, 20.7°, 23.8° and 27.3°.
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- METHOD OF SYNTHESIZING TETRAHYDROBIOPTERIN
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The present disclosure provides a method that efficiently produces (6R)-tetrahydrobiopterin in high yield and purity. The method includes the step of hydrolyzing diacetylbiopterin to biopterin under basic conditions in a biphasic mixture comprising an organic phase and an aqueous phase. After substantially complete hydrolysis of diacetylbiopterin, the aqueous phase containing biopterin can be separated from the organic phase containing most of the organic impurities, which avoids the time-consuming step of isolating biopterin as a solid. The aqueous solution containing biopterin is stereoselectively hydrogenated to (6R)-tetrahydrobiopterin under basic conditions and high hydrogen pressure in the presence of a metal catalyst (e.g., a platinum catalyst). To improve the purification of an acid addition salt of (6R)-tetrahydrobiopterin (e.g., (6R)-tetrahydrobiopterin dihydrochloride), any residual salts (e.g., sodium salts) in the aqueous solution after the hydrogenation reaction can be removed by contacting the aqueous solution with an ion (e.g., cation) exchange resin or column. Alternatively, removal of residual salts from the aqueous solution can be omitted if an organic amine (e.g., diethylamine or triethylamine) rather than an inorganic base is used in the hydrolysis and/or hydrogenation reactions.
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Page/Page column 10-11
(2009/08/16)
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- A convenient synthesis of optically active biopterin
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Naturally occurring L-erythro-biopterin is synthesized using regioselective pteridine-ring formation from the chiral α,(β-epoxyaldehyde intermediate which is prepaccred from ethyl L-lactate via Sharpless epoxidation.
- Shiro, Yuichi,Urano, Fumi,Kuroda, Yasuhiro,Murata, Shizuaki
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experimental part
p. 1329 - 1335
(2009/07/05)
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- Method for producing L-biopterin
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To provide a method for producing L-biopterin on a large industrial scale by using a reagent which is inexpensive and easy to handle, without requiring a use of any particular equipment or plants.
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Page/Page column 5
(2008/06/13)
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- PROCESSES FOR PREPARING TETRAHYDROBIOPTERIN, AND ANALOGS OF TETRAHYDROBIOPTERIN
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Process for the preparation of tetrahydrobiopterin from neopterin and/or 6-substituted pterins with an improved yield and a high stereoselectivity. Also disclosed herein are novel individual intermediates prepared in the preparation of tetrahydrobiopterin, such as selectively protected neopterin useful for the preparation of tetrahydrobiopterin.
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Page/Page column 28-29
(2008/06/13)
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- Novel regio- and stereoselective synthesis of 6-substituted pteridines and naturally occurring L-erythro-biopterin
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Condensation of 2,4,5-triamino-6-butoxypyrimidine with various 2-formyloxiranes followed by oxidation with iodine affords 2-amino-4-butoxy-6-(1-hydroxyalkyl)pteridines regioselectively. Naturally occurring L-erythro-biopterin is synthesized from (1S,2S,3S)-2-formyl-3-(1-hydroxyethyl)oxirane. The reaction proceeds via 5,6-dihydropteridine, and the mechanism is discussed with the help of molecular orbital calculations.
- Murata,Sugimoto,Ogiwara,Mogi,Wasada
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p. 303 - 308
(2007/10/02)
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- Synthesis of (-)-Biopterin Using (S)-Ethyl Lactate as a Starting Material
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(-)-Biopterin was synthesized from (1S,2S)-1-(1,3-dithian-2-yl)propane-1,2-diol 5 (=C), which was derived from commercially available (S)-ethyl lactate.Diol 5 (=C) was converted to 15 through a six-step sequence.Ketone 15 was submitted to condensation with 3,5,6-triaminopyrimidinol (TAP, 2), and followed by oxidation to afford isopropylidenebiopterin (16).Finally, 16 was deprotected to give (-)-biopterin (1).
- Kikuchi, Haruhiko,Mori, Kenji
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p. 2095 - 2100
(2007/10/02)
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- A New Synthesis of (-)-Biopterin Employing 5-Deoxy-L-ribose as a Key Intermediate
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(-)-Biopterin (1) was synthesized from 5-deoxy-L-ribose (6) which was derived from commercially available D-ribose (2) employing the highly stereoselective Grignard reaction of 2,3-O-cyclohexylidene-D-ribose (3) with methylmagnesium iodide.
- Mori, Kenji,Kikuchi, Haruhiko
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p. 1267 - 1270
(2007/10/02)
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- Synthesis of (-)-Biopterin
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The synthesis of (-)-biopterin (1) was accomplished by employing (1S,2S)-1-(2-furyl)-2-(trityloxy)-1-propanol (6), derived from ethyl (S)-lactate, as building block for the side chain.
- Mori, Kenji,Kikuchi, Haruhiko
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p. 963 - 968
(2007/10/02)
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- Quinonoid Dihydrobiopterin, an Important Metabolic Intermediate of Biopterin Cofactor in the Aromatic Hydroxylation of Amino Acids
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p-Quinonoid (6R)-dihydrobiopterin hydrochloride was synthesized from (6R)-5,6,7,8-tetrahydrobiopterin dihydrochloride by hydrogenperoxide in the presence of potassium iodide.Several characters of quinonoid dihydrobiopterin were examined.
- Matsuura, Sadao,Murata, Shizuaki,Sugimoto, Takashi
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p. 585 - 588
(2007/10/02)
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- 169. Pterinechemistry Part 84 A New, Regiospecific Synthesis of L-Biopterin
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Pure L-biopterin was obtained in 42percent yield by the condensation of 5-deoxy-L-arabinose-phenylhydrazone-triacetate with 4-hydroxy-2,5,6-triaminopyrimidine, followed by iodine oxidation of the formed tetrahydropterin derivative to 1',2'-O-diacetyl-L-biopterin.Deacetylation was carried out with NH4OH.
- Schircks, Bernhard,Bieri, Jost H.,Viscontini, Max
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p. 1639 - 1643
(2007/10/02)
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- Pteridines, LXXV. - Synthesis and Properties of Biopterin and Biopterin Analogs
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The synthesis of biopterin (6), its 2-N,N-dimethyl- (8) and 4-thioxo derivative (19) as well as biolumazine (7) is described.The side chain of biopterin can be modified by reaction of α-acetoxy-isobutyryl chloride to yield 6-(L-threo-2-acetoxy-1-chloropropyl)pterin (10), which can be used as a starting material for further derivatisations. 2,1',2'-Triacylbiopterins (14, 16) possess a hydrolytically labile N-acyl group.The newly synthesized compounds were characterized by pK-determinations, UV, and NMR spectra.
- Kappel, Mathias,Mengel, Rolf,Pfleiderer, Wolfgang
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p. 1815 - 1825
(2007/10/02)
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- Pterins. VIII. The Absolute Configuration at C 6 of Natural 2-Amino-6--5,6,7,8-tetrahydropteridin-4(3H)-one (L-erythro-5,6,7,8-tetrahydrobiopterin)
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The conformation of the side chain of 5,6,7,8-tetrahydrobiopterin (6) in 0.5 M DCl/D2O is predominantly quasi-equatorial (deduced from 3J (13C 4a, 1H 6) 1.1 Hz), and is the same as that of the methyl group in 2-methyl-1,2,3,4-tetrahydroquinoxaline and in 2-amino-6-methyl-5,6,7,8-tetrahydropteridin-4(3H)-one in the same solvent.Because (-)-2S)-2-methyl-1,2,3,4-tetrahydroquinoxaline (4) and (-)-(6S)-2-amino-6-methyl-5,6,7,8-tetrahydropteridin-4(3H)-one (5) have the same conformation and negative c.d. spectra (Θ 248 nm and 263 nm respectively) as does the natural 5,6,7,8-tetrahydrobiopterin (Θ minimum at 265 nm) in 0.1 M hydrochloric acid, then the absolute conformations of the tetrahydropyrazine rings and the absolute configurations at the chiral crntres C2, C6, and C6 of compounds (4),(5) and (6) respectively are the same.Hence the absolute configuration at C6 in natural 5,6,7,8-tetrahydrobiopterin is R.A convenient synthesis of biopterrin on a gram scale is described.
- Armarego, Wilfred L. F.,Waring, Paul,Paal, Bela
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p. 785 - 793
(2007/10/02)
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