WO2002051852A1 - Procede de production d'un derive de saccharide non naturel - Google Patents

Procede de production d'un derive de saccharide non naturel Download PDF

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Publication number
WO2002051852A1
WO2002051852A1 PCT/JP2001/011561 JP0111561W WO02051852A1 WO 2002051852 A1 WO2002051852 A1 WO 2002051852A1 JP 0111561 W JP0111561 W JP 0111561W WO 02051852 A1 WO02051852 A1 WO 02051852A1
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group
atom
formula
derivative
halogenated
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PCT/JP2001/011561
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English (en)
Japanese (ja)
Inventor
Hideki Umetani
Tomoyuki Ando
Junya Fujiwara
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Mitsui Chemicals, Inc.
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Publication of WO2002051852A1 publication Critical patent/WO2002051852A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
    • C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring

Definitions

  • the present invention relates to a method useful for producing a non-naturally occurring mono-monophosphorylated sugar derivative in a anomeric selective manner, a compound used therefor, and a method for producing the same.
  • Unnatural mono-phosphorylated saccharide derivatives are expected to be used as raw materials for the production of antiviral agents and enzyme inhibitors.
  • nucleosides having an unnatural sugar structure have attracted attention as antiviral drugs.
  • compounds having a thioxolan structure have been reported in EP 3 82526, Drug soft furniture 2000, 25 (8), 855-857, In WO 0009494 and the like, compounds having a dioxolane structure are known from JP-A-8-501086, Drug soft Future 2000, 25 (5), 454-461, WO 0039143 and the like.
  • the common problem with the chemical production methods 1) to 5) is that the anomeric selectivity of ⁇ -form ⁇ 3 is affected by the functional group adjacent to the 1-position, and the desired isomer has good selectivity.
  • the point is that it is difficult to consider a general synthesis method to obtain a good result.
  • the presence of 2-acetoxy group or 2-acetamino group is indispensable, and in addition, 2-position deoxy sugar may be unstable. The range is small. Therefore, it is difficult to control the anomeric selectivity in the synthesis of 1-phosphorylated form of 2-hydroxypyroxypyranose, so column chromatography purification is required, and only low yields are obtained [Chem Zve sti, Vol. 28 (1), P115 (1974), Izv. Akad. Nauk SSSR, Ser. Khim., Vol. 8, P1843 (1975)].
  • the mono-phosphorylated form of 2-position deoxyfuranoses which is more unstable and difficult to control the selectivity than the mono-phosphorylated form of 2-position deoxypyranose, has been produced by chemical production. Has not been reported. Regarding 6), it is difficult to supply nucleosides other than very limited liponucleosides such as inosine, and only limited 1-phosphorylated sugar derivatives such as report-1-phosphate can be produced. In addition, the cost of the raw material nucleosides themselves is not satisfactory because of their high cost.
  • An object of the present invention is to provide a method for selectively producing a non-naturally occurring mono-phosphorylated sugar derivative by an anomer. Another object of the present invention is to provide a non-natural 1-phosphorylated saccharide derivative useful as a raw material for producing an antiviral agent or an enzyme inhibitor. Another object of the present invention is to provide a method for producing a non-natural octogenated saccharide derivative useful for anomeric selective production of a non-natural 1-phosphorylated saccharide derivative, and a non-natural halogenated saccharide obtained by the method. An object of the present invention is to provide a derivative and a sugar derivative useful for producing the non-natural halogenated sugar derivative.
  • a desired 1-phosphorylated saccharide derivative can be obtained with high anomeric selectivity from a halogenated sugar such as a single anomeric chlorinated sugar by using a means such as performing a phosphorylation reaction under conditions.
  • the present invention includes the following embodiments.
  • the anomeric configuration of the halogenated sugar derivative represented by the formula (1) is inverted by the phosphorylation, and one of the desired a-form or / 3 form of the monophosphorylated sugar derivative represented by the formula (2) is obtained.
  • a method for producing a non-natural type 1-monophosphorylated saccharide derivative characterized in that: Formula (1) represents either the Q! Or / 3 isomer of the octogenated saccharide derivative.
  • the mono-phosphorylated saccharide is converted from the ⁇ -form of the halogenated saccharide derivative. Either one of the following two cases is obtained: a case where 8 derivatives of the derivative are obtained, a case where a single monophosphorylated sugar derivative is obtained from 0 of the halogenated sugar derivative.
  • X and ⁇ each independently represent an oxygen atom or a sulfur atom
  • R represents a hydrogen atom, an alkyl group, an alkenyl group, or an acyl group
  • W represents a hydroxyl-protecting group.
  • X and Y each independently represent an oxygen atom or an io atom, Z represents a halogen atom, and Wa represents a nitrobenzoyl group.
  • X and Y each independently represent an oxygen atom or a sulfur atom
  • R represents a hydrogen atom, an alkyl group, an alkenyl group, or an acyl group
  • W represents a substituted aromatic acyl group.
  • 1 mono-phosphorylated sugar derivative refers to a sugar derivative in which the 1-hydroxyl group is phosphorylated among the residues of unnatural sugars, and unless otherwise specified, monomer 1, dimer 1 Trimers may also be included or a mixture of them may be used, and the ratio is not particularly limited.
  • the “protecting group” of the hydroxyl group represented by W in the above formula (1) or the like refers to a protecting group that is removed by a chemical method such as hydrogenolysis, hydrolysis, or photolysis.
  • a chemical method such as hydrogenolysis, hydrolysis, or photolysis.
  • examples of such a group include an acyl group, a silyl group, an alkyl group, an aralkyl group, and a carbonyl group. Of these, an aliphatic acyl group, an aromatic acyl group, an alkoxyalkyl group, a halogenated alkyl group, and an aralkyl group are preferred. And an alkoxycarbonyl group and an aralkyl carbonyl group.
  • Examples of the aliphatic acryl group that can function as the above-mentioned protective group include an alkyl group or a halogen-substituted lower alkylcarbonyl group.
  • Specific examples of the above alkylcarbonyl group include acetyl group, propionyl group, butyryl group, isoptyryl group, pentanoyl group, pivaloyl group, valeryl group, isovaleryl group, octanoyl group, nonylcarbonyl group, decylcarbonyl group, and 3-methylethyl group.
  • halogen-substituted lower alkylcarbonyl group examples include a chloroacetyl group, a dichloroacetyl group, a trichloroacetyl group, and a trifluoroacetyl group.
  • aromatic acyl group capable of functioning as the protective group examples include an arylcarbonyl group, a halogen-substituted arylaryl group, a lower alkylated arylaryl group, and a lower alkoxyarylcarbonyl group as a substituted aromatic acyl group. And a nitrated arylcarbonyl group, a lower alkoxylated arylcarbonyl group, and an arylphenylcarbonyl group.
  • arylcarbonyl group examples include a benzoyl group, a mononaphthoyl group, and a 3-naphthoyl group.
  • halogen-substituted arylcarbonyl group examples include 2-fluorobenzoyl group, 3-fluorobenzoyl group, 4-fluorobenzoyl group, and 2-chlorobenzoyl group. , 3-cyclobenzoyl group, 4-monobenzoyl group, 2-bromobenzoyl group, 3-bromobenzoyl group, 4-bromobenzoyl group, 2,4-dichlorobenzoyl group, 2,6-dichlorobenzoyl group, 3 , 4-dicro-benzoyl group and 3,5-dichloro-benzoyl group.
  • lower alkylated arylcarbonyl group examples include 2-toluene.
  • examples thereof include a methyl group, a 3-toluoyl group, a 4-toluoyl group, and a 2,4,6-trimethylbenzoyl group.
  • lower alkoxyarylcarbonyl group examples include a 2-anisyl group, a 3-anisyl group, a 4-anisyl group, and the like.
  • arylnitrocarbonyl group examples include 2-nitrobenzoyl group, 3-nitrobenzoyl group, 4-nitrobenzoyl group, and 3,5-dinitrobenzoyl group.
  • arylated carbonyl group examples include a 4-phenylbenzoyl group.
  • silyl group that can function as the protective group examples include a lower alkylsilyl group and a lower alkylsilyl group substituted with an aryl group.
  • the lower alkylsilyl group examples include a trimethylsilyl group, a triethylsilyl group, an isopropyldimethylsilyl group, a t-tert-butyldimethylsilyl group, a methyldiisopropylpropylsilyl group, and a triisopropylsilyl group.
  • lower alkylsilyl group substituted with the aryl group examples include a diphenylmethylsilyl group, a diphenylisopropylsilyl group, and a phenyldiisopropylsilyl group.
  • Examples of the aralkyl group capable of functioning as the above protective group include an aralkyl group substituted with a lower alkyl group, an aralkyl group substituted with a lower alkoxy group, an aralkyl group substituted with a nitro group, an aralkyl group substituted with a halogen, and a cyano group. And an aralkyl group substituted with a group.
  • these groups include 2-methylbenzyl group, 3-methylbenzyl group, 4-methylbenzyl group, 2,4,6-trimethylbenzyl group, 2-methoxybenzyl group, and 3-methoxybenzyl group.
  • 4-methoxybenzyl group, 2-nitrobenzene Benzene, 3-nitrobenzyl, 4-nitrobenzyl, 2-chlorobenzyl, 3-cyclobenzyl, 4-cyclobenzyl, 2-bromobenzyl, 3-bromo Examples include a benzyl group, a 4-bromobenzyl group, a 2-cyanobenzyl group, a 3-cyanobenzyl group, and a 4-cyanobenzyl group.
  • Examples of the aralkyloxycarbonyl group capable of functioning as the above protecting group include an aralkyloxycarbonyl group substituted with a lower alkyl group and an aralkyloxycarbonyl group substituted with a lower alkoxy group. And aralkyloxycarbonyl substituted with a nitro group, aralkyloxycarbonyl substituted with a halogen, and aralkyloxycarbonyl substituted with a cyano.
  • Specific examples thereof include a 2-methylbenzyloxycarbonyl group, a 3-methylbenzyloxycarbonyl group, a 4-methylpentyloxycarbonyl group, a 2,4,6-trimethylbenzyloxycarbonyl group, and a 2-methoxybenzyloxycarbonyl group.
  • the lower alkoxycarbonyl group examples include a methoxycarbonyl group, an ethoxycarbonyl group, a propoxycarbonyl group, a butoxycarbonyl group, a sec-butoxycarbonyl group, and a tert-butoxycarbonyl group.
  • a halogen-substituted alkoxy group capable of functioning as the above protecting group Specific examples of the alkoxycarbonyl group in which a 2,2,2-trichloroethoxycarbonyl group is substituted with a lower alkylsilyl group include a 2-trimethylsilylethoxycarbonyl group and the like.
  • alkyl group that can function as the protective group examples include an unsubstituted alkyl group; an alkoxyalkyl group such as a methoxymethyl group, an ethoxymethyl group, a 2-methoxyethyl group, and a 2-methoxyethoxymethyl group; —Halogenated alkyl groups such as tricycloethyl group; lower alkyl groups substituted with aryl groups such as benzyl group, ⁇ -naphthylmethyl group, 6-naphthylmethyl group, diphenylmethyl group and triphenylmethyl group Is mentioned.
  • an aromatic acyl group is preferable, and a 4-nitrobenzoyl group is more preferable.
  • a lower alkyl group is preferred, and a lower alkyl group in a lower alkyl group or a lower alkoxy group is preferably a linear alkyl group having 1 to 6 carbon atoms.
  • a branched or branched alkyl group is preferred.
  • R in one OR in the formula (4) is an alkyl group, an acyl group, or an alkenyl group in which —OR can be substituted with a halogen atom by a halogenating agent.
  • the alkyl group and the acyl group various specific groups exemplified as the alkyl group and the acyl group that can be used as the protective group described above can be used.
  • As the alkenyl group a lower alkenyl group, preferably having 2 to 6 carbon atoms. Alkenyl groups can be used.
  • a more preferred R is an acetyl group.
  • the halogen atom represented by Z represents a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. More preferably, it is a chlorine atom.
  • the 1-phosphorylated saccharide derivative in the present invention usually forms a salt.
  • the salt in this case refers to a salt formed by a phosphate group in the molecule of the compound.
  • Salts include alkali metal salts such as sodium, potassium, and lithium; alkaline earth metal salts such as magnesium, calcium, and barium; metal salts such as aluminum and iron; ammonium salts; , Secondary or tertiary alkylamine salts I can do it.
  • primary amines include alkylamines such as methylamine, ethylamine, propylamine, isopropylamine, butylamine, hexylamine, octylamine, cycloalkylamines such as cyclohexylamine, and benzylamine. Can be mentioned.
  • secondary amine examples include dialkylamines such as getylamine, diisopropylamine, dibutylamine, dihexylamine, and dioctylamine, and cyclic amines such as dicine and N-methylpiperazine.
  • Tertiary amines include trimethylamine, triethylamine, tripropylamine, N-ethyldiisopropylamine, triptylamine, trihexylamine, trioctylamine, N-ethyldicyclohexylamine, N-methylpiperidine, N-methylmorpholine.
  • Tertiary alkylamines such as phosphorus, N, N, N ', N'-tetramethylethylenediamine, aniline, N, N-dimethylaniline, N, N-diethylaniline, N, N-dibutylaniline
  • Anilines such as N, N-dioctylaniline, salts of pyridines such as pyridine, 2,6-dimethylpyridine, 2,4,6-lutidine, nicotinamide, glycine, alanine, proline, lysine Amino acids, such as arginine, glutamine, cinchonidine, 1_ (1 naphthyl) ethylamine
  • optically active amines such as 1-phenylethylamine, all of which include monovalent or divalent salts.
  • Phosphoric acid that can be used in this reaction is preferably one having a small amount of water, such as orthophosphoric acid, but is not particularly limited.
  • the base that can be used in this reaction is not particularly limited as long as it does not inhibit the reaction and functions as a deoxidizing agent.
  • the inorganic base is an alkali metal, an alkaline earth metal carbonate, or water.
  • organic bases such as oxides include tertiary alkylamines, anilines, pyridines, and optically active amines.
  • the dehydrating agent that can be used in this reaction is preferably used when water mixed in from a solvent or an additive adversely affects the reaction.
  • the dehydrating agent is not particularly limited as long as it has a water-adsorbing property or a reactivity with water, but preferably includes molecular sieves or phosphorus pentoxide.
  • This phosphorylation reaction is usually performed in the presence of a solvent.
  • the solvent to be used is not particularly limited as long as it does not inhibit the reaction and dissolves the starting material to some extent. Examples thereof include aliphatic hydrocarbons such as hexane and heptane, benzene, toluene, and xylene.
  • Aromatic hydrocarbons such as ren, anisol, methylene chloride, chloroform, carbon tetrachloride, halogenated hydrocarbons such as dichloroethane, cyclobenzene, dichlorobenzene, ethyl formate, ethyl acetate, acetic acid Esters such as propyl, n-butyl acetate, and getyl carbonate, ethers such as getyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane, diglyme, acetonitrile, propionitrile, isoptyronitrile Nitriles such as formamide, N, N-di Amides such as methylformamide, N, N-dimethylacetamide, N-methyl-2-pyrrolidone, N-methylpyrrolidinone, N, N-dimethyl-12-imidazolidinone, acetone, 2-butenonone,
  • the reaction temperature is not particularly limited, and is usually in the range of ⁇ 80 ° C. to 60 °, preferably ⁇ 10 ° C. to 25 ° C.
  • the reaction time varies depending on the starting materials, the types of reagents and solvents, and the reaction temperature. It is usually achieved in 1 minute to 24 hours, preferably in 10 minutes to 2 hours.
  • the ratio of the halogenated saccharide derivative represented by the formula (1) to the phosphoric acid can be carried out as long as the phosphoric acid is at least 1 equivalent to the compound (1).
  • the compound of the formula (1): phosphoric acid 1: 1 to 1:15 is preferable.
  • the ratio of phosphoric acid to salt clogging is an important factor in suppressing the epimeri- lation reaction.
  • the epimeri- lation reaction proceeds. Therefore, by reacting with phosphoric acid using an equimolar or more base, the epimerization reaction is suppressed, and the selectivity of the desired anomer ( ⁇ -form or jS-form) of the monophosphorylated saccharide derivative can be suppressed. That is, the content of the desired anomer in the resulting anomer mixture can be significantly improved.
  • the desired anomer of the 1-phosphorylated saccharide derivative can be purified by performing a salt exchange reaction and extracted as a phosphate of a base different from the base used in the reaction system.
  • Examples of the base used herein include the aforementioned inorganic bases, primary alkylamines, secondary alkylamines, tertiary alkylamines, anilines, pyridines, amino acids, and optically active amines.
  • the salts include monovalent and divalent salts.
  • the hydroxyl-protecting group represented by W may be removed by treating with a base in a water-soluble solvent.
  • the base is sodium carbonate
  • Alkali metal carbonates such as potassium carbonate, lithium hydroxide, sodium hydroxide, alkali metal hydroxides such as potassium hydroxide, ammonia water, ammonium hydroxides such as tetra-n-butylammonium hydroxide
  • the reaction can be performed using the above-mentioned inorganic bases, primary alkylamines, secondary alkylamines, tertiary alkylamines, and the like.
  • the solvent to be used is not particularly limited as long as it is used in a usual hydrolysis reaction, but preferably, alcohols such as water, methanol, ethanol, n-propanol and isopropanol, and the above-mentioned alcohols are used. Ethers can be used.
  • the reaction temperature and the reaction time vary depending on the starting material and the base used, etc., and are not particularly limited.
  • aralkyl group or aralkyloxycarbonyl group When the above-mentioned aralkyl group or aralkyloxycarbonyl group is used as the 7K acid group-protecting group, it can be removed by catalytic reduction using a metal catalyst, for example.
  • the catalyst preferably, palladium carbon, Raney nickel, platinum oxide, platinum black, rhodium aluminum monoxide, triphenylphosphine-rhodium chloride, barium palladium monosulfate and the like can be used.
  • the pressure is not particularly limited, but the solvent generally used is not particularly limited as long as it is one used in a usual hydrolysis reaction.
  • the solvent is water, methanol, ethanol, ⁇ -propanol, or isopropanol. Alcohols such as ethyl and the aforementioned ethers and esters can be used.
  • the reaction temperature and reaction time vary depending on the starting material, the base used, and the like, and are not particularly limited.
  • the reaction is carried out at 110 ° C. to 100 ° C. for 1 hour to 5 days.
  • the silyl group can be removed by using a compound such as tetrafluoro-n-butylammonium which generates a fluorine anion.
  • the reaction solvent is not particularly limited as long as it does not inhibit the reaction, and the above-mentioned ethers can be used.
  • the reaction temperature and reaction time are not particularly limited, but are usually from 10 to 50 T, and are completed in 10 minutes to 10 hours.
  • the phosphate group in the molecule of the product is obtained as a salt of a base present in the reaction system, but may be changed to a salt of another base if desired. You can also take it out.
  • Examples of the base used at this time include the above-mentioned inorganic bases, primary alkylamines, secondary alkylamines, tertiary alkylamines, anilines, pyridines, amino acids, optical activity Amines can be mentioned, and the salts formed include monovalent and divalent salts.
  • the halogenated saccharide derivative as a raw material for producing the monophosphorylated saccharide derivative represented by the formula (1) can be produced by halogenating the saccharide derivative represented by the above formula (4). it can.
  • the sugar derivative used in the halogenation step include a raw material consisting of either one of the anomers (that is, a raw material consisting of only the body or a raw material consisting of only the / 3 body), and a anomeric mixture (that is, the ⁇ body and] 3). Body mixture).
  • the halogenating agent to be used may be one usually used for halogenating natural and unnatural sugars, and is not particularly limited. Specifically, it is a hydrogen halide such as hydrogen chloride and hydrogen bromide, and an acid halogen compound such as oxalyl bromide, oxalyl chloride, acetyl chloride, acetyl bromide, propionyl chloride, and phosgene; and trimethylsilane chloride.
  • a hydrogen halide such as hydrogen chloride and hydrogen bromide
  • an acid halogen compound such as oxalyl bromide, oxalyl chloride, acetyl chloride, acetyl bromide, propionyl chloride, and phosgene
  • trimethylsilane chloride trimethylsilane chloride
  • halogenated trialkylsilanes such as trimethylsilane iodide; phosphorus halides such as trichlorosilane and oxychloride; and inorganic halides such as thionyl chloride, sulfuryl chloride, and titanium tetrachloride.
  • the above-mentioned halogenating agent may be used as it is, or it may be in the form of a Vilsmeier type 1 reagent obtained by reacting an acid halide compound with dimethylformamide. Methanol, ethanol, water or the like may be reacted with the agent to generate hydrogen halide in the reaction system and used.
  • the equivalent used is not limited as long as it is 1 equivalent or more, but 3 equivalents or more and 15 equivalents from the viewpoint of reaction rate and economics. The following is desirable.
  • the solvent used is not limited as long as it is an aprotic solvent.
  • saturated hydrocarbon solvents such as hexane and heptane / cyclohexane, 1,2-dichloroethane, halogen solvents such as methylene chloride and chloroform, dimethyl ether / diisopropyl ether, t Examples include ether solvents such as monobutyl methyl ether. Further, two or more aprotic solvents may be mixed.
  • the reaction temperature is not lower than 170 ° C. and not higher than the boiling point of the solvent, preferably not lower than 110 ° C. and not higher than 50 ° C.
  • the mixture of the spleen and the) 3 body (the ratio of the spleen and the body as in the comparative example 1) Gives 1: 1 power, 2: 1), and stereoselective synthesis is difficult. Therefore, by focusing on the difference in physical properties existing between the anomeric isomers of the halogenated sugar derivative represented by the formula (1) and utilizing the difference, that is, from the anomeric mixture, one of the ⁇ -form or the / 3-form is obtained. By selectively crystallizing the compound, the equilibrium between the anomer and the mixture is inclined, and it is possible to selectively produce either the ⁇ 1> body or the / 3 body.
  • this anomeric-selective production method it is possible to adopt a method of isolating the target halogenated sugar derivative by a simple operation only by filtration, so that an operation such as concentration under reduced pressure is not required.
  • an operation such as concentration under reduced pressure is not required.
  • the reaction solution was partitioned between water and form, and the form layer was concentrated under reduced pressure.
  • acetone and cyclohexylamine (2.39 ml, 20.9 mmol) were added, and the precipitated cyclohexylamine salt of the target product (6) was collected by filtration.
  • mold 1-monophosphorylated saccharide derivative the raw material compound useful for use in the said method, and its production method can be provided.

Abstract

L'invention concerne un procédé selon lequel un dérivé de saccharide halogéné non naturel, obtenu par sélection d'un anomère, est soumis à une phosphorylation dans des conditions telles que l'épimérisation est empêchée pour permettre la formation de l'anomère désiré d'un dérivé de saccharide 1-phosphorylé. Cette technique peut être mise en oeuvre dans la production avec sélection d'un anomère d'un dérivé de saccharide 1-phosphorylé non naturel pouvant être utilisé comme matériau de départ pour la constitution d'un agent antivirus, d'un inhibiteur enzymatique, etc.
PCT/JP2001/011561 2000-12-27 2001-12-27 Procede de production d'un derive de saccharide non naturel WO2002051852A1 (fr)

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JP2000398259 2000-12-27
JP2000398258 2000-12-27
JP2001-098229 2001-03-30
JP2001098229 2001-03-30
JP2000-398259 2001-03-30
JP2000-398258 2001-03-30

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1178051A2 (fr) * 2000-02-10 2002-02-06 Mitsui Chemicals, Inc. Procede de production selective d'un anomere derive d'un sucre 1-phosphoryle

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0382526A2 (fr) * 1989-02-08 1990-08-16 Biochem Pharma Inc 1,3-oxathiolanes substitués doués de propriétés antivirales
WO1992008717A1 (fr) * 1990-11-13 1992-05-29 Biochem Pharma Inc. 1,3-oxathiolanes substitues et 1,3-dithiolanes substitutes presentant des caracteristiques antivirales
WO1995029176A1 (fr) * 1994-04-20 1995-11-02 Biochem Pharma Inc. 1,3-oxathiolanes substituees a proprietes antivirales
WO1997021706A1 (fr) * 1995-12-14 1997-06-19 Biochem Pharma Inc. PROCEDE ET COMPOSITION POUR LA SYNTHESE DE NUCLEOSIDES CONTENANT UN GROUPE DIOXOLANNE AVEC UNE CONFIGURATION $g(b)
WO2000047759A1 (fr) * 1999-02-11 2000-08-17 Shire Biochem Inc. Synthese stereoselective d'analogues nucleosidiques
WO2001058920A2 (fr) * 2000-02-10 2001-08-16 Mitsui Chemicals, Inc. Procede de production selective d'un anomere derive d'un sucre 1-phosphoryle

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0382526A2 (fr) * 1989-02-08 1990-08-16 Biochem Pharma Inc 1,3-oxathiolanes substitués doués de propriétés antivirales
WO1992008717A1 (fr) * 1990-11-13 1992-05-29 Biochem Pharma Inc. 1,3-oxathiolanes substitues et 1,3-dithiolanes substitutes presentant des caracteristiques antivirales
WO1995029176A1 (fr) * 1994-04-20 1995-11-02 Biochem Pharma Inc. 1,3-oxathiolanes substituees a proprietes antivirales
WO1997021706A1 (fr) * 1995-12-14 1997-06-19 Biochem Pharma Inc. PROCEDE ET COMPOSITION POUR LA SYNTHESE DE NUCLEOSIDES CONTENANT UN GROUPE DIOXOLANNE AVEC UNE CONFIGURATION $g(b)
WO2000047759A1 (fr) * 1999-02-11 2000-08-17 Shire Biochem Inc. Synthese stereoselective d'analogues nucleosidiques
WO2001058920A2 (fr) * 2000-02-10 2001-08-16 Mitsui Chemicals, Inc. Procede de production selective d'un anomere derive d'un sucre 1-phosphoryle

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1178051A2 (fr) * 2000-02-10 2002-02-06 Mitsui Chemicals, Inc. Procede de production selective d'un anomere derive d'un sucre 1-phosphoryle
EP1178051A4 (fr) * 2000-02-10 2003-05-28 Mitsui Chemicals Inc Procede de production selective d'un anomere derive d'un sucre 1-phosphoryle
US7038039B2 (en) 2000-02-10 2006-05-02 Mitsui Chemicals, Inc. Process for selectively producing 1-phosphorylated sugar derivative anomer and process for producing nucleoside

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