WO2006104166A1 - Support pour separation par cristallisation et procede pour separer un compose - Google Patents

Support pour separation par cristallisation et procede pour separer un compose Download PDF

Info

Publication number
WO2006104166A1
WO2006104166A1 PCT/JP2006/306348 JP2006306348W WO2006104166A1 WO 2006104166 A1 WO2006104166 A1 WO 2006104166A1 JP 2006306348 W JP2006306348 W JP 2006306348W WO 2006104166 A1 WO2006104166 A1 WO 2006104166A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
carrier
crystallization
crystallization separation
solution
Prior art date
Application number
PCT/JP2006/306348
Other languages
English (en)
Japanese (ja)
Inventor
Kazuhiro Chiba
Original Assignee
National University Corporation, Tokyo University Of Agriculture And Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by National University Corporation, Tokyo University Of Agriculture And Technology filed Critical National University Corporation, Tokyo University Of Agriculture And Technology
Priority to JP2007510542A priority Critical patent/JPWO2006104166A1/ja
Publication of WO2006104166A1 publication Critical patent/WO2006104166A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B63/00—Purification; Separation; Stabilisation; Use of additives
    • C07B63/02—Purification; Separation; Stabilisation; Use of additives by treatment giving rise to a chemical modification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups

Definitions

  • the present invention relates to a carrier for crystallization separation and a method for separating a compound, and more specifically, a crystal that is a compound that rapidly changes from a liquid phase state to a solid phase state due to changes in solution composition and Z or solution temperature.
  • the present invention relates to a crystallization separation support and a method for separating a compound using the crystallization separation support.
  • Such solidification (crystallization) of a specific component dissolved in a solution is realized by satisfying certain conditions in relation to chemical properties, physical properties, and solvents of the compound.
  • a carrier molecule having a linker has been proposed in which changes in the solvent composition are sensitively detected and the dissolved state and the insolubilized (crystallized) state change reversibly.
  • Various compounds can be bound to such a carrier molecule through a linker, and the bound compound is dissolved in an insolubilized (crystallized) state or vice versa with the carrier molecule.
  • the state can be changed easily.
  • such a compound bound to a carrier reversibly repeats a dissolved state and an insoluble state (crystallized state) under almost the same conditions even when the chemical structure is changed by successive chemical reactions. be able to.
  • Non-Patent Document 1 a method using a polymer soluble in a solvent such as polyethylene glycol is known (Non-Patent Document 1). reference).
  • Non-Special Reference 1 “Liquia— phase combinatorial synthesisj Hyunsoo Han, Mary M. Wolfe, Sydney Brenner, and Kim D. Janda, Proc. Natl. Acad. Sci. USA, Vol. 92, pp. 6419— 6423, July 1995 Chemistry
  • Non-Patent Document 1 when a polymer such as polyethylene glycol described in Non-Patent Document 1 is used as a carrier, the compound binds to the carrier due to the non-uniformity of the polymer. In the as-is state, it was difficult to identify the compound. In addition, since polyethylene glycol is hydrophilic, it is difficult to carry out an anhydrous reaction and has a problem of complicated handling.
  • the present invention has been made in view of the above problems, and a chemical reaction can be performed in a liquid phase, and a specific substance is selectively solidified from the liquid phase after the reaction is completed. (Crystallization) facilitates the separation of a specific substance, and further allows the compound to be identified by structural analysis or the like while the separated compound remains bound to the carrier. ⁇ ⁇ To provide a method for separating compounds.
  • the present inventors have intensively studied to solve the above problems. As a result, if a support for crystallization separation is used that has a reaction site that binds to another compound and reversibly changes between a liquid phase state and a solid phase state with changes in solution composition and Z or solution temperature, Solve the above issues As a result, the present invention has been completed. More specifically, the present invention provides the following.
  • a carrier for crystallization separation that is a compound that reversibly changes from a liquid phase state to a solid phase state with changes in solution composition and Z or solution temperature, and binds to other compounds.
  • the reaction site has one or more atoms selected from carbon atom, oxygen atom, sulfur atom, and nitrogen atom force, and includes carbon atom, nitrogen atom, sulfur atom, and A carrier for crystallization separation that binds to another compound via any one of nitrogen atoms.
  • the crystallization separation support of (1) binds to another compound at a reaction site, and remains in the state of being bound to the other compound, with a change in solution composition and Z or solution temperature. State Force Reversibly changes to a solid state. Therefore, it is possible to selectively crystallize other compounds that react with the reaction site.
  • the other compound bonded to the crystallization separation support of (1) has a liquid phase state and a solid phase under substantially the same conditions even when the chemical structure is changed by sequential chemical reaction.
  • the state can be reversibly repeated. For this reason, it is not necessary to examine the crystallization conditions based on the properties unique to each compound.
  • the carrier for crystallization separation of (2) has a saccharide skeleton.
  • “having a saccharide skeleton” means a structure partially including a skeleton derived from a saccharide.
  • a structure in which a saccharide is used as a starting material and at least one hydroxyl group of the saccharide itself or a hydrogen atom of the hydroxyl group is substituted at the reaction site can be exemplified.
  • the carrier for crystallization separation of (2) has a saccharide skeleton, it is easy to introduce a large number of hydrocarbon groups. For this reason, the hydrophobicity of the carrier for crystallization separation can be improved.
  • the carrier for crystallization separation of (3) has pentose or hexose as a saccharide skeleton.
  • saccharides by using pentose or hexose as a skeleton, it is easy to obtain and introduction of hydrocarbon groups is facilitated.
  • X is one or more atoms selected from carbon, oxygen, sulfur and nitrogen atoms
  • R to R are carbon atoms having 1 to 60 carbon atoms which may have the same or different substituents.
  • R to R At least one of R to R, at least one of R to R, and a small number of R to R, respectively.
  • the carrier for crystallization separation of (4) is a derivative having a pentose or hexose skeleton.
  • R to R in the formula may be the same or different and may have a substituent.
  • the support for crystallization separation of (4) may have at least one substituent having 8 or more carbon atoms, and may have a hydrocarbon group or at least one substituent having 8 or more carbon atoms. And may have an acyl group.
  • the support for crystallization separation in (4) exhibits hydrophobicity. Therefore, by adding a highly polar solvent after completion of the reaction, crystallization is facilitated. can do.
  • the carbon number is preferably 12 or more, more preferably 18 or more.
  • X is a carbon, oxygen, sulfur or nitrogen atom
  • Y is a reaction site having one or more atoms selected from carbon, oxygen, sulfur, and nitrogen atoms,
  • R is a hydrocarbon group having 1 to 60 carbon atoms
  • the carrier for crystallization separation of (5) has a reactive site that binds to another compound and is a hydrocarbon having 1 to 60 carbon atoms bonded via a carbon, oxygen, sulfur, or nitrogen atom. Has a group. By having a long-chain hydrocarbon group having 1 to 60 carbon atoms, the carrier for crystallization separation of (5) exhibits hydrophobicity, and can therefore be dissolved at a high concentration in many organic solvents.
  • the carbon number is preferably 12-30, more preferably 20-30.
  • a method for separating a compound wherein the crystallization separation carrier according to any one of (1) to (5) is dissolved in a soluble solvent to prepare a carrier solution;
  • a compound separation method comprising: a bonding step of bonding another compound to a reaction site of a separation carrier; and a crystallization step of crystallizing the carrier to which the other compound is bonded.
  • the compound separation method (6) is a separation method using the crystallization separation carrier of the present invention.
  • a specific substance can be selectively crystallized. Therefore, it is possible to separate only a specific substance while leaving a soluble component in the liquid phase, thereby avoiding complicated separation process.
  • the method for separating compounds of (6) is an innovative technology in the separation and purification of biochemical substances, search for drug candidate substances, construction of new chemical synthesis reaction methods and continuous peptide synthesis methods, etc. It can be.
  • the method for separating a compound of (7) includes a step of separating the crystallization carrier force of the compound accompanying the crystallization separation carrier of the present invention after crystallization. This makes it possible to obtain the target compound obtained by synthesis or the like as a single compound. Further, the carrier for crystallization separation after separation can be reused thereafter.
  • An impurity removal step for removing impurities from the solution is further included before the crystallization step.
  • (6) The method for separating a compound according to (6) or (7).
  • the method for separating a compound of (8) includes a step of removing impurities from the solution before crystallization from the solution of the crystallization separation carrier of the present invention and the compound. This makes it possible to increase the purity of a substance that is subsequently crystallized (a complex of a carrier for crystallization separation and a compound).
  • the compound is separated by the means for changing the solution composition and the means for changing Z or the solution temperature.
  • the force is also (8) V. Method.
  • crystallization is carried out by changing the solution composition and Z or the solution temperature.
  • the carrier for crystallization separation of the present invention reacts sensitively to changes in solution composition and Z or solution temperature. For this reason, by using means for changing the composition and Z or temperature of the solution, it becomes possible to crystallize the support for crystallization separation accompanied with the compound, so that it is soluble and not bonded to the support for crystallization separation. Substances can be easily separated from specific compounds while remaining in solution.
  • a solvent having high affinity is added to a solution in which a complex in which the compound and the carrier for crystallization separation are dissolved. Since the solution composition can be changed by adding a solvent having high affinity, it is possible to crystallize the carrier for crystallization separation accompanied with the compound.
  • the means for changing the solution composition is to concentrate the soluble solvent.
  • the method for separating a compound according to (9), wherein the means for changing the solution temperature is to cool the solution.
  • the compound separation method of (12) has a crystallization step of cooling the solution. By cooling the solution, the solution temperature can be changed, and the crystallization separation carrier with the compound can be crystallized.
  • a chemical reaction can be performed in a liquid phase, and a specific substance is selectively solidified (crystallized) from the liquid phase after the reaction is completed.
  • separation of the specific substance can be facilitated.
  • the compound can be identified by structural analysis or the like while the separated compound remains bound to the carrier. For this reason, there is no need to study crystallization conditions based on the properties unique to each compound, so the process development can be facilitated.For example, research and development of pharmaceuticals by compound library synthesis etc. Can be promoted, and in turn can contribute to technological innovation in the biochemical and chemical industries.
  • the separation method of the compound of the present invention can be an innovative technique in the separation and purification of biochemical substances, the search for drug candidates, the construction of new chemical synthesis reaction methods, continuous peptide synthesis methods, etc. .
  • the carrier for crystallization separation of the present invention is a carrier for crystallization separation that is a compound that reversibly changes from a liquid phase state to a solid phase state with a change in solution composition and Z or solution temperature, and other compounds.
  • the reaction site has one or more atoms selected from a carbon atom, an oxygen atom, a sulfur atom, and a nitrogen atom, and a carbon atom, a nitrogen atom, a sulfur atom, and And a carrier for crystallization separation that binds to another compound via any of the nitrogen atoms.
  • reaction site The reaction site for binding to the other compound of the crystallization separation carrier of the present invention has one or more atoms selected from a carbon atom, an oxygen atom, a sulfur atom, and a nitrogen nuclear power, May contain more than one.
  • the size of the reaction site is not particularly limited as long as it has a portion serving as a reaction site for binding to another compound in a part of the reaction site.
  • the position of the reaction site for binding to other compounds in the reaction site is not particularly limited, but it exists at the end of the reaction site for the purpose of facilitating the reaction. It is preferable.
  • reaction site At the reaction site, it is bonded to other compounds via carbon atoms, nitrogen atoms, sulfur atoms, and / or nitrogen atoms.
  • the structure of the reaction site having any of a carbon atom, a nitrogen atom, a sulfur atom, and a nitrogen atom that binds to another compound at the reaction site is not particularly limited. For example, a hydroxyl group, an amino group And carboxyl group.
  • the number of reaction sites is not particularly limited, and may include a plurality of reaction sites.
  • the number of reaction sites with other compounds in the analysis / separation carrier is preferably one.
  • the crystallization separation carrier in the present invention preferably has a saccharide skeleton.
  • “having a saccharide skeleton” means a structure including a skeleton derived from a saccharide in part.
  • Sugars include polyalcohol itself, polyalcohol aldehydes, ketones, acids, their derivatives, condensates, and the like.
  • when it has a saccharide skeleton it may be a monosaccharide or a oligosaccharide or a polysaccharide obtained by condensing a plurality of these.
  • the saccharide skeleton in the crystallization separation carrier of the present invention is not particularly limited.
  • V is preferably pentose or hexose! /.
  • a carrier for crystallization separation can be obtained by introducing a reactive site into the saccharide using saccharide as a starting material.
  • the introduction position of the reaction site is not particularly limited.
  • the method for introducing the reaction site is not particularly limited. For example, a method of substituting at least one hydroxyl group of a saccharide or a hydrogen atom of the hydroxyl group with a reactive site can be mentioned.
  • crystallization separation carrier of the present invention include those represented by the following chemical formulas (A) to (F).
  • X is one or more atoms selected from carbon, oxygen, sulfur and nitrogen atoms
  • R to R are carbon atoms having 1 to 60 carbon atoms which may have the same or different substituents.
  • R to R At least one of R to R, at least one of R to R, and a small number of R to R, respectively.
  • the carrier for crystallization separation shown in the above (A) to (F) is a derivative having a pentose or hexose skeleton.
  • the carbon number of the carbon chain of R to R in the formula is usually 1 to 60.
  • the carrier for crystallization separation shown in (A) to (F) has at least one hydrocarbon group which may have a substituent having 8 or more carbon atoms, or at least one carbon number. It may have 8 or more substituents and may have an acyl group.
  • the presence of long chain hydrocarbon groups or long chain acyl groups renders the crystallization separation support hydrophobic.
  • the carbon number of the long chain portion is usually 8 or more, preferably 12 or more, more preferably 18 or more.
  • the method for producing the compounds (A) to (F) is not particularly limited.
  • a protecting group such as trityl chloride
  • X is a carbon, oxygen, sulfur or nitrogen atom
  • Y is a reaction site having one or more atoms selected from carbon, oxygen, sulfur, and nitrogen atoms
  • R is a hydrocarbon group having 1 to 60 carbon atoms
  • ⁇ represents an integer of 1 to 5.
  • the carrier for crystallization separation shown in (G) has a reactive site that binds to another compound and has 1 to 5 carbon atoms bonded via carbon, oxygen, sulfur, or nitrogen atoms. Has 60 hydrocarbon groups. The presence of a long-chain hydrocarbon group having 1 to 60 carbon atoms makes the support for crystallization separation hydrophobic. For this reason, the carrier for crystallization separation having a long-chain hydrocarbon group can be dissolved at a high concentration in many organic solvents.
  • the long chain portion usually has 1 to 60 or more carbon atoms, preferably 12 to 30 and more preferably 20 to 30.
  • the method for producing the compound (G) is not particularly limited.
  • a phenol derivative having a functional group serving as a binding site is reacted with a halogenated hydrocarbon under basic conditions to obtain an alkoxyphenyl derivative, and then bonded by a known functional group conversion method. It is possible to synthesize the carrier for crystallization separation (G) by converting the functional group as the site.
  • the compound separation method of the present invention comprises a dissolution step of preparing the carrier solution by dissolving the crystallization separation carrier of the present invention in a soluble solvent, and other compounds at the reaction site of the crystallization separation carrier. And a crystallization step of crystallizing the carrier to which the other compound is bonded.
  • the soluble solvent used in the dissolving step in the present invention is not particularly limited as long as it can dissolve the crystallization separation carrier of the present invention.
  • examples thereof include halogenated hydrocarbons, chain ethers, cyclic ethers, cyclic hydrocarbons having 4 to 40 carbon atoms, and chain hydrocarbons. More specifically, for example, dichloromethane, tetrahydrofuran and the like can be mentioned.
  • These solvents which may be used alone, may be used in combination with cyclohexane, methylcyclohexane, decalin and the like.
  • the concentration at which the carrier for crystallization separation of the present invention is dissolved in a soluble solvent is the solvent used,
  • the force that can be appropriately selected according to the carrier for crystallization separation and the nature of the compound to be combined with the crystallization separation carrier, etc. Usually is 0.01-0.lgZml.
  • any other compound having a portion that reacts with the reaction site may be bonded to the reaction site of the crystallization separation support dissolved in the soluble solvent in the previous step.
  • Various chemical reactions in the liquid phase can be used without particular limitation. For example, a method of bonding by forming an ester bond or an amide bond can be mentioned.
  • the crystallization step in the present invention is a step of crystallizing the compound bonded to the crystallization separation carrier in the bonding step, which is the previous step, while keeping the state accompanied with the carrier.
  • the crystallization process in the present invention is not particularly limited as long as the crystallization process can be performed while maintaining the state in which the compound to be crystallized is bonded to the crystallization separation support.
  • the means for changing the solution composition and the means for changing Z or the solution temperature can be preferably used.
  • a means for changing the composition of the solution in which the carrier for crystallization separation to which the compound to be crystallized is dissolved dissolves. If there is, it is not particularly limited.
  • preferred means for changing the solution composition include, for example, a high affinity for the soluble solvent used for dissolving the crystallization separation carrier in the dissolution step.
  • Means for further adding a large solvent may be mentioned.
  • the solvent having high affinity may be the same solvent as the solvent used as the soluble solvent or a different solvent.
  • dichloromethane or tetrahydrofuran is used alone as a soluble solvent, or when these solvents are used in combination with cyclohexane, methylcyclohexane, decalin, or the like, as a highly friendly solvent, acetonitrile, dimethyl It is possible to use formamide, methanol or the like.
  • another preferred means for changing the solution composition is, for example, conversion to a crystallization target.
  • the concentration means that a part or all of the solvent is distilled off.
  • impurities contained in the solution may be precipitated together. Therefore, it is preferable to include a step of removing impurities before performing the crystallization step.
  • the means for changing the solution temperature preferably used is a means capable of changing the temperature of the solution in which the carrier for crystallization separation in which the compound to be crystallized is bonded is dissolved. If there is, there is no particular limitation.
  • a means for cooling the solution can be mentioned. For example, when cyclohexane is used as a soluble solvent for dissolving the carrier for crystallization separation, crystallization can be achieved by cooling to 5 ° C.
  • ODS particles silicon gel with octadecyl group bonded to the surface
  • a substance that becomes the nucleus of crystallization such as carrasbees, is added. Crystal growth can be facilitated.
  • the compound, the crystallization separation carrier, and the crystallization separation carrier in a state in which the compound to be crystallized obtained in the crystallization step is bonded. It is preferable to include the step of separating into two.
  • the method for separating the compound from the crystallization separation support is not particularly limited as long as it can break the bond between the compound and the crystallization separation support.
  • the bond can be released by acid treatment.
  • an impurity removal step for removing impurities before carrying out the crystallization step.
  • impurities contained in the solution may be precipitated together.
  • the compound to be crystallized is bound. Impurities are precipitated together with the crystals of the carrier for crystallization separation. Therefore, by removing impurities in advance before carrying out the crystallization step, it is possible to increase the purity of the crystal of the crystallization separation support to which the compound to be obtained after crystallization is bonded.
  • the method for removing impurities is not particularly limited.
  • the crystallization separation support to which the compound to be crystallized is dissolved dissolves the entire solution with a solvent.
  • the method of washing can be mentioned.
  • Trityl chloride 100g, Methyl-a-D-glucoside (Compound l) 89g (l. 3eq.), Dimethylaminopyridine (DMAP) 4.6g (0 leq.) was placed in a 1 liter eggplant flask. To this, 400 ml of dehydrated dichloromethane and 190 ml (4 eq.) Of triethylamine (TEA) were added, and the flask was further washed with 100 ml of dichloromethane (DCM) and stirred well.
  • DCM dichloromethane
  • the reaction solution initially had a white precipitate (TEA hydrochloric acid), and then gradually turned orange. After confirming the completion of the reaction by TLC (silica gel thin layer chromatography), the salt was removed by filtration.
  • the white compound on the obtained filter paper was washed with about 100 ml of hexane (n-hexane), and the liquid phase was concentrated. To this, 100 ml of hexane (n-hexane) and 100 ml of 2-propanol (2-propanol) were added and dissolved by heating at about 70 ° C., followed by recrystallization at room temperature to obtain the desired compound 3 Obtained.
  • the yield was 80%.
  • Octadecanoic acid 6- [4 (4-hydroxymethyl-phenoxy) -butyryloxymethyl] 2-methoxy 4,5-bisocta which is the carrier for crystallization separation of the present invention obtained in Example 1
  • Decanoyloxytetrahydropyran 3-yl ester (compound 7) 0.174 g (0.3 mmol) was dissolved in 20 ml of dichloromethane (DCM).
  • the target carrier—Val—Pro—Fmoc that is, Octadecanoic acid 6-methoxy-2- [4 1 (4 — ⁇ 3-Methyl-2-[[(Pyrrolidine-2-carbol) -amino] -Butylyloxymethyl ⁇ -Phenoxy) -Butyloxymethyl] —4,5-Bisoctadecanoxyl tetrahydropyran 3-Ilster (compound 10) was obtained. The obtained compound 10 was 473 mg (0.30 mmol), and the yield was 59%.
  • DCM dichloromethane
  • DMF dimethylformamide
  • the carrier for crystallization separation and the method for separating a compound of the present invention include compound library synthesis and the like. It is possible to promote research and development of pharmaceuticals, etc., and thus contribute to technological innovation in Seikagaku Corporation. It can also be an innovative technology for the separation and purification of biochemical substances, the search for drug candidates, the construction of new chemical synthesis reaction methods and continuous peptide synthesis methods.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Saccharide Compounds (AREA)

Abstract

L’invention concerne un support pour la séparation par cristallisation qui est un composé changeant de façon réversible d’un état de phase liquide à un état de phase solide en fonction du changement dans la composition et/ou la température de la solution. Le support de la séparation par cristallisation a un site réactif qui se combine avec un autre composé, le site réactif ayant un ou plusieurs atomes choisis parmi les atomes de carbone, oxygène, soufre et azote et se combine avec un autre composé via l’un quelconque des atomes de carbone, oxygène, soufre et azote. Lorsque le support est utilisé, il est possible de réaliser une réaction chimique dans une phase liquide, de solidifier (cristalliser) une substance spécifique et de la séparer facilement d’une phase liquide après la fin de la réaction. De plus, le composé séparé peut être identifié, par exemple, en soumettant le composé à l’état lié au support à une analyse structurelle.
PCT/JP2006/306348 2005-03-29 2006-03-28 Support pour separation par cristallisation et procede pour separer un compose WO2006104166A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2007510542A JPWO2006104166A1 (ja) 2005-03-29 2006-03-28 晶析分離用担体及び化合物の分離方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005-095924 2005-03-29
JP2005095924 2005-03-29

Publications (1)

Publication Number Publication Date
WO2006104166A1 true WO2006104166A1 (fr) 2006-10-05

Family

ID=37053422

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2006/306348 WO2006104166A1 (fr) 2005-03-29 2006-03-28 Support pour separation par cristallisation et procede pour separer un compose

Country Status (2)

Country Link
JP (1) JPWO2006104166A1 (fr)
WO (1) WO2006104166A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006015283A (ja) * 2004-07-02 2006-01-19 Nokodai Tlo Kk 化合物の分離用担体および化合物の分離方法
WO2007034812A1 (fr) * 2005-09-20 2007-03-29 National University Corporation, Tokyo University Of Agriculture And Technology Support de séparation, procédé de séparation d’un composé et procédé de synthèse de peptide utilisant le support
JP2008212815A (ja) * 2007-03-02 2008-09-18 Nokodai Tlo Kk 有機合成用反応装置及び有機合成反応方法
WO2011078295A1 (fr) 2009-12-25 2011-06-30 味の素株式会社 Composé de benzyle
US8093435B2 (en) 2006-03-24 2012-01-10 Jitsubo Co., Ltd. Reagent for organic synthesis and method of organic synthesis reaction with the reagent
WO2012029794A1 (fr) 2010-08-30 2012-03-08 味の素株式会社 Composé aromatique contenant une ramification spécifique
WO2012157723A1 (fr) 2011-05-17 2012-11-22 味の素株式会社 Procédé de production d'oligonucléotides
US8569453B2 (en) 2009-03-12 2013-10-29 Ajinomoto Co., Inc. Fluorene compound
US8722934B2 (en) 2009-03-30 2014-05-13 Ajinomoto Co., Inc. Diphenylmethane compound
WO2014189142A1 (fr) 2013-05-24 2014-11-27 味の素株式会社 Procédé de fabrication de morpholino-oligonucléotide
US9353148B2 (en) 2011-05-31 2016-05-31 Ajinomoto Co., Inc. Method for producing peptide
US9353147B2 (en) 2011-05-31 2016-05-31 Ajinomoto Co., Inc. Method for producing peptide
EP3266792A4 (fr) * 2015-03-04 2018-05-09 Jitsubo Co., Ltd. Procédé de synthèse peptidique
WO2020101032A1 (fr) 2018-11-16 2020-05-22 味の素株式会社 Procédé de production d'un peptide cyclisé ayant une liaison intramoléculaire s-s

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002212198A (ja) * 2001-01-15 2002-07-31 Jsr Corp 核酸の分離方法および核酸分離用担体
JP2006015283A (ja) * 2004-07-02 2006-01-19 Nokodai Tlo Kk 化合物の分離用担体および化合物の分離方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000044493A (ja) * 1998-07-27 2000-02-15 Asahi Chem Ind Co Ltd 化合物ライブラリー合成用保護基

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002212198A (ja) * 2001-01-15 2002-07-31 Jsr Corp 核酸の分離方法および核酸分離用担体
JP2006015283A (ja) * 2004-07-02 2006-01-19 Nokodai Tlo Kk 化合物の分離用担体および化合物の分離方法

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2006015283A (ja) * 2004-07-02 2006-01-19 Nokodai Tlo Kk 化合物の分離用担体および化合物の分離方法
WO2007034812A1 (fr) * 2005-09-20 2007-03-29 National University Corporation, Tokyo University Of Agriculture And Technology Support de séparation, procédé de séparation d’un composé et procédé de synthèse de peptide utilisant le support
US8633298B2 (en) 2005-09-20 2014-01-21 Jitsubo Co., Ltd. Carrier for separation, method for separation of compound, and method for synthesis of peptide using the carrier
JPWO2007034812A1 (ja) * 2005-09-20 2009-03-26 国立大学法人東京農工大学 分離用担体、化合物の分離方法、及びこれを用いたペプチド合成方法
JP4500854B2 (ja) * 2005-09-20 2010-07-14 Ｊｉｔｓｕｂｏ株式会社 分離用担体
US9284348B2 (en) 2005-09-20 2016-03-15 Jitsubo Co., Ltd. Method for synthesis of peptide using a carrier
US8293948B2 (en) 2006-03-24 2012-10-23 Jitsubo Co., Ltd. Reagent for organic synthesis and method of organic synthesis reaction with the reagent
US8093435B2 (en) 2006-03-24 2012-01-10 Jitsubo Co., Ltd. Reagent for organic synthesis and method of organic synthesis reaction with the reagent
JP2008212815A (ja) * 2007-03-02 2008-09-18 Nokodai Tlo Kk 有機合成用反応装置及び有機合成反応方法
US9029504B2 (en) 2009-03-12 2015-05-12 Ajinomoto Co., Inc. Fluorene compound
US8569453B2 (en) 2009-03-12 2013-10-29 Ajinomoto Co., Inc. Fluorene compound
US9670121B2 (en) 2009-03-30 2017-06-06 Ajinomoto Co., Inc. Diphenylmethane compound
US8722934B2 (en) 2009-03-30 2014-05-13 Ajinomoto Co., Inc. Diphenylmethane compound
US9169187B2 (en) 2009-03-30 2015-10-27 Ajinomoto Co., Inc. Method of making peptides using diphenylmethane compound
WO2011078295A1 (fr) 2009-12-25 2011-06-30 味の素株式会社 Composé de benzyle
US9206230B2 (en) 2009-12-25 2015-12-08 Ajinomoto Co., Inc. Benzylic compound
US8859732B2 (en) 2009-12-25 2014-10-14 Ajinomoto Co., Inc. Benzylic compound
US9499579B2 (en) 2010-08-30 2016-11-22 Ajinomoto Co., Inc. Branched chain-containing aromatic compound
CN103080058B (zh) * 2010-08-30 2017-04-12 味之素株式会社 含有支链的芳香族化合物
US8546534B2 (en) 2010-08-30 2013-10-01 Ajinomoto Co., Inc. Branched chain-containing aromatic compound
CN103080058A (zh) * 2010-08-30 2013-05-01 味之素株式会社 含有支链的芳香族化合物
US10711033B2 (en) 2010-08-30 2020-07-14 Ajinomoto Co., Inc. Branched chain-containing aromatic compound
WO2012029794A1 (fr) 2010-08-30 2012-03-08 味の素株式会社 Composé aromatique contenant une ramification spécifique
JP5929756B2 (ja) * 2010-08-30 2016-06-08 味の素株式会社 分岐鎖含有芳香族化合物
WO2012157723A1 (fr) 2011-05-17 2012-11-22 味の素株式会社 Procédé de production d'oligonucléotides
JP2017036322A (ja) * 2011-05-31 2017-02-16 味の素株式会社 ペプチドの製造方法
US9353147B2 (en) 2011-05-31 2016-05-31 Ajinomoto Co., Inc. Method for producing peptide
US9353148B2 (en) 2011-05-31 2016-05-31 Ajinomoto Co., Inc. Method for producing peptide
WO2014189142A1 (fr) 2013-05-24 2014-11-27 味の素株式会社 Procédé de fabrication de morpholino-oligonucléotide
EP3266792A4 (fr) * 2015-03-04 2018-05-09 Jitsubo Co., Ltd. Procédé de synthèse peptidique
US11098078B2 (en) 2015-03-04 2021-08-24 Jitsubo Co., Ltd. Peptide synthesis method
WO2020101032A1 (fr) 2018-11-16 2020-05-22 味の素株式会社 Procédé de production d'un peptide cyclisé ayant une liaison intramoléculaire s-s

Also Published As

Publication number Publication date
JPWO2006104166A1 (ja) 2008-09-11

Similar Documents

Publication Publication Date Title
WO2006104166A1 (fr) Support pour separation par cristallisation et procede pour separer un compose
EP2570416B1 (fr) Dérivé de bisfurane comme inhibiteur de protéase du VIH et son intermédiaires
WO2005070859A1 (fr) Supports fluores et procedes de production de derives d'oligonucleotide utilisant ces supports
WO2007034812A1 (fr) Support de séparation, procédé de séparation d’un composé et procédé de synthèse de peptide utilisant le support
KR100426030B1 (ko) 락톤계 당화합물에서의 키랄성 전환방법
WO2007046554A1 (fr) Procédé pour la production d'un composé de dibenzoxépinopyrrole, intermédiaire pour la production du composé et procédé pour la production de l'intermédiaire
KR20200100048A (ko) 신규 알킬디페닐메탄 보호제
KR20140098131A (ko) 스테롤 유도체의 제조 공정
US9834561B2 (en) Process for preparing ibrutinib and its intermediates
KR102421025B1 (ko) 신규 트리틸 보호제
CN106699604B (zh) 一种沙库比曲及其中间体的制备方法
CN109912603B (zh) 一种使用n-甲氧基酰胺作为氮源合成新型生物活性分子的实用方法
CN110511193A (zh) 一种α-酮硫代酰胺类化合物及其合成方法
JP4534024B2 (ja) 化合物の分離用担体および化合物の分離方法
CN113861093B (zh) 一种多取代γ-丁内酰胺的合成方法
CN111285846B (zh) 一种2-(2-吲哚基)-乙酸酯衍生物及其合成方法
WO1998032736A1 (fr) Procede de production de derives d'acide benzylsuccinique
CN110172062B (zh) 一种单氟代螺环化合物的合成方法及其中间体
JP4163113B2 (ja) 新規化合物及びその製造方法
JPS61161278A (ja) ３‐置換インドールの調製方法
TW202325709A (zh) 化合物、包括其的固態載體以及製備核酸的方法
KR20000065816A (ko) 파라 및/또는 메타-치환 시아노페닐알라닌 유도체의 새로운 합성방법
CN118005704A (en) Synthesis method of heterocyclic carbon glycoside compound with single configuration
CN114621312A (zh) 一种寡肽烷基侧链的选择性修饰方法
TW568913B (en) Method for preparing 13-ester derivatives of milbemycines

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 2007510542

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: RU

122 Ep: pct application non-entry in european phase

Ref document number: 06730296

Country of ref document: EP

Kind code of ref document: A1