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WO1999007750A1 - Resines perfluorees utilisees comme supports des reactions en phase solide - Google Patents

Resines perfluorees utilisees comme supports des reactions en phase solide Download PDF

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Publication number
WO1999007750A1
WO1999007750A1 PCT/GB1998/002263 GB9802263W WO9907750A1 WO 1999007750 A1 WO1999007750 A1 WO 1999007750A1 GB 9802263 W GB9802263 W GB 9802263W WO 9907750 A1 WO9907750 A1 WO 9907750A1
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Prior art keywords
resin
group
solid
reaction
phase
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Ceased
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English (en)
Inventor
David Gani
Mahmoud Ahktar
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University of St Andrews
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University of St Andrews
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Priority to AU86356/98A priority Critical patent/AU8635698A/en
Publication of WO1999007750A1 publication Critical patent/WO1999007750A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/545—Synthetic resin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/042—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers characterised by the nature of the carrier
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/18—Introducing halogen atoms or halogen-containing groups
    • C08F8/20—Halogenation
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/30—Introducing nitrogen atoms or nitrogen-containing groups
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/30—Introducing nitrogen atoms or nitrogen-containing groups
    • C08F8/32—Introducing nitrogen atoms or nitrogen-containing groups by reaction with amines
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F8/00—Chemical modification by after-treatment
    • C08F8/34—Introducing sulfur atoms or sulfur-containing groups
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F2810/00—Chemical modification of a polymer
    • C08F2810/30—Chemical modification of a polymer leading to the formation or introduction of aliphatic or alicyclic unsaturated groups

Definitions

  • the present invention concerns the preparation and use of chemically functionalised polymeric resins for use in solid-phase chemical synthesis .
  • the third problem concerns the deconvolution of the library which essentially requires identifying the chemical structure of the molecule, within the mixture, that shows the required biological activity or other desired property.
  • This method of deconvolution is time consuming and unnecessarily clumsy.
  • Another way of effecting deconvolution is to tag the polymeric support with chemicals which can be used to decode the synthetic chemical history of the particular particle of polymeric support, independently to being able to carry out an activity assay on the material attached to the support.
  • Such methods have been described in the literature. Since typical particles of polymeric support are referred to as "resin beads" and are commercially available in the size 70-400 microns, deconvolution by such methods is a fiddly job requiring accurate and expensive instrumentation.
  • the fourth problem concerns checking the efficiency of the chemical synthesis and, in essence, this is a problem of scale.
  • Individual beads possess, at most, only a few to several nanomoles of material attached to them and, therefore, it is extremely difficult to check either the efficiency of the synthesis or the purity of the synthetic product. In highly sensitive biological screening assays this can be a very serious problem as the impurity could be responsible for a positive result.
  • the best way to overcome this last problem is to perform syntheses on a larger scale such that some material can be put aside for characterisation and analysis. While this solution offers very many advantages, the practice of a larger scale combinatorial syntheses requires the design and use of microreactors or other small individual reaction chambers into which larger quantities of resin material can be confined.
  • Microreactors may be designed to either A) contain resin beads within a porous enclosure which is pervious to reagent solutions and solvents, or B) microreactors may be themselves giant porous assemblies of resin material.
  • microreactors of type A for solid-phase syntheses on a polymeric support, in which the resin beads are enclosed within the microreactor, have been described and include microreactors constructed from polypropylene, which is not inert and microreactors construed from almost totally inert frit glass and polytetrafluoroethylene.
  • many reports supply little information on the design of the microreactors or on how they were used in synthesising libraries of compounds.
  • the main purpose of some reports was to describe the incorporation of an addressable microchip into the microreactors which could be written to and read using radio waves. This elegant idea does require the microreactors to be of a size large enough to contain the addressable chip, which in itself is not a problem, but demands the use of sophisticated and moderately expensive equipment.
  • the system was optimised for use with POSAM ® (Permutational Organic Synthesis in Addressable Microreactors) where microreactor identification is performed visually, but is also suitable for use with radio-addressable microreactors or any other type of microreactor tagging system or solid support tagging system or hybrid tagging system including those which utilise laser or mass spectrometric or radioisotope or magnetic resonance or any other spectroscopic or fluorimetric or related methodology which uses electromagnetic radiation to detect the identity of, or communicate with, the microreactor.
  • POSAM ® Permutational Organic Synthesis in Addressable Microreactors
  • the polymer base for almost all of the commercially available resin materials, whether modified with polyethylene glycol appendages to give Tentagel resins or otherwise, is 1-2% divinylbenzene cross-linked polystyrene in which approximately one in ten of the phenyl rings derived from the styrene is modified to give a benzyl moiety to which different functional groups are attached.
  • the chloromethyl (or benzyl chloride) derivative is called Merrifield resin and this material and its derivatives are mechanically fragile and swell several fold in most organic solvents (eg dimethylformamide, tetrahydrofuran, dichloromethane) but not all organic solvents (eg methanol) .
  • reaction kinetics for chemical reactions performed on polystyrene-based resins is drastically effected by how swollen the resin becomes as it is solvated by the particular organic solvent.
  • Polystyrene is also chemically sensitive to some hot organic solvents and is modified by solutions of the very strong nucleophiles/bases and the protic and Lewis acids commonly used in conventional synthesis.
  • polymer supports have found use in biochemical applications such as the preparation of affinity columns for isolating and/or binding to proteins, DNA, RNA etc. These systems are usually used in aqueous buffer solutions and the polymer support is usually derived from polysaccharide, polyamide, polyacrylate or polyacrylamide solid phases. These are, in general, unsuitable for organic synthesis.
  • the present invention seeks to overcome several disadvantages associated with present practices in solid-phase synthesis.
  • the present invention concerns the development of alternative resin materials for use in synthesis that comprise a modified perfluorocarbon polymer backbone instead of polystyrene or other conventional polymers, in order to confer increased physical and/or chemical stability to new chemically functionalised resins derived from these resin materials.
  • the present invention concerns the development of resin materials containing perfluorocarbon polymer backbones which are modified with new functional groups, to allow a wider range of chemical manipulations and reactions to be performed in solid- phase synthesis.
  • the synthetic steps could be performed in open vessels (for example in standard laboratory flasks), in closed vessels (for example in chromatography columns) or in type A microreactors where the resin material is contained within a porous container.
  • the invention also encompasses microreactors of type B that are themselves giant porous assemblies of otherwise inert resin material.
  • the present invention also concerns the development of new resin materials that possess a modified perfluorocarbon polymer backbone (compared to commercially available resins used for solid-phase synthesis) to confer increased physical and chemical stability, and which can be formed into macroscopic shapes which are porous and which can be used in place of the microreactor in the POSAM ® system or in standard laboratory flasks, for example, while still conferring all of the advantages of scale of synthesis and of labelling that are associated with microreactors.
  • a modified perfluorocarbon polymer backbone compared to commercially available resins used for solid-phase synthesis
  • the invention relates to a polytetrafluoroethylene resin comprising a side chain having a sulphonamide or sulphonanilinide moiety like the one of general formula I:
  • n and m are each integers of from 1 to several hundred (for example up to 200); p is 0 or 1; X is a spacer group; Y is a spacer group; R a may be H or a lower alkyl group (eg a C_ 6 alkyl); R b may be any moiety bearing at least one reactive functional group; or R a and R b may together form a C 4 - C 6 cyclic ring which may optionally contain further heteroatoms (eg N, S or 0) and/or may optionally be substituted by a moiety containing at lest one reactive functional group.
  • p is 0 or 1
  • X is a spacer group
  • Y is a spacer group
  • R a may be H or a lower alkyl group (eg a C_ 6 alkyl)
  • R b may be any moiety bearing at least one reactive functional group; or R a and R b may together form a C 4 - C 6 cyclic
  • n and m are each integers of from 1 to several hundred (for example up to 200);
  • X is a spacer group; and
  • R c is a Ci. 20 carboxy acid, carboxy ester, aliphatic alcohol, ether or amino acid derivative.
  • the resin has the general formula III:
  • n and m are each integers from 1 to several hundreds (for example up to 200);
  • X is a spacer group;
  • Y is a linear or branched C x _ 6 aliphatic hydrocarbon group, optionally interrupted by heteroatoms;
  • R d is an aryl group, substituted by a reactive functional moiety such as a carboxy group, carboxyl group, sulphonyl group, amine, amide, thioester or the like.
  • the spacer groups X and Y may be an suitable moiety, including branched or linear C ⁇ o hydrocarbon chains, optionally interrupted by heteroatoms, especially 0, S or N.
  • X is a group -CF 2 -Z-CF 2 - where Z is a perfluoroalkylether group; or X is a group -[CF 2 -CF(CF 3 )-0] v -(CF 2 ) w - where v is 0 or 1 and w is 1 to 4; or X is a group -[CF 2 ] 7 - where y is 1 to 8; or X is a group -CHQ-(CH 2) q- where q is 1 to 10 and Q is H or an alkyl group, eg. a C x _ 6 alkyl group.
  • the invention further relates to the use of a polytetrafluoroethylene resin bearing a reactive functional group as a support matrix for solid-phase chemical reactions.
  • the invention further relates to a method of producing a solid-phase reactant for a solid-phase chemical reaction, the reactant comprising a polytetrafluoroethylene resin-substrate complex. wherein said complex is produced by reacting a precursor substrate with a functional group on the polytetrafluoroethylene resin.
  • the invention further relates to a method of chemical synthesis involving a chemical reaction wherein one of the substrates of the reaction is in the form of a solid-phase polytetrafluoroethylene resin substrate complex.
  • the invention further relates to a microreactor comprising a resin material as a support matrix for a solid-phase chemical reaction, wherein the resin material is a polytetrafluoroethylene resin.
  • the invention further relates to such a microreactor wherein the resin a resin according to the invention as described above.
  • Type A microreactors work extremely well for the solid- phase synthesis of libraries of compounds containing hundreds of members and can deliver tens of milligrams of each library member.
  • POSAM ® apparatus all components are constructed from glass and polytetrafluoroethylene (PTFE) but the resin beads have, up until now, been based upon the original Merrifield (functionalised polystyrene) type and, therefore, are not as chemically robust as would be desirable.
  • PTFE polytetrafluoroethylene
  • a further problem is the size of the existing Merrifield resin beads and their mechanical fragility. These are related issues. For example, one could imagine preparing the entire microreactor (type B) from the resin polymer (eg Merrifield resin or a derivative or precursor) itself. The further requirements for use in the POSAM ® apparatus would be:
  • Merrifield resins are composed of polystyrene cross- linked with 1% or 2% divinylbenzene .
  • the cross-linking is required to provide mechanical strength, but the resin beads remain fragile even when sizes are kept to below 130 microns (0.13mm) diameter. Larger beads can be prepared but these break-up very easily and microreactors of type B would have a useful minimum size of 5mm and an optimum size of 13mm (or more) in diameter, ie 40-100 times larger (or more) in diameter to the beads currently available.
  • the amount of cross- linking in the resin can be increased but this leads to both increased brittleness and decreased solvent accessibility.
  • PTFE polytetrafluoroethylene
  • Dupont and other chemical companies have developed NafionTM and similar perfluorinated functionalised resins for use as electrolyte membrane separators in electrochemical cells used by the chloralkali industry.
  • the membranes are essentially a PTFE polymer backbone containing perfluorinated side-chains which possess an anionic group (carboxylate or sulfonate) which allows the passage of only cations but not anions through the membrane.
  • the NafionTM membrane itself has to withstand very harsh chemical conditions (25% NaOH) and considerable temperatures for long periods of time (several months). We have now recognised that this material and derivatives thereof is ideal for the construction of new resins for use in solid-phase organic synthesis (and in particular for use in POSAM ® microreactors ) .
  • the new resins described herein exhibit the following properties : i) excellent chemical stability; ii) mechanically robust up to the temperatures required for a range of useful solid-phase chemistries (180°C); iii) does not solvate to the extent of polystyrene resins (the PTFE backbone is neither lipophilic or hydrophilic so that swelling is minimal); and iv) the acid halide and ester forms of PTFE modified with appended sulfonic and carboxylic side-chains are heat-processible (unlike PTFE).
  • NafionTM is extremely expensive and possesses a rather low level of chemical functionalisation (approx. 0.8 milliequivalents per gramme, before customisation), nonetheless, NafionTM (see Formulae A below) was considered to be a good model to check the chemical stability and functionalisation properties of modified future polytetrafluoroethylene (PTFE) -based functionalised resins.
  • PTFE polytetrafluoroethylene
  • Huoropolymcr Spa ⁇ rcr ai ⁇ perfluoroal l ether gro ⁇ ps Backbone (these differ for different types of Nafion) Formula A General Structure of Nafion & Similar Resin Materials Accordingly, Nafion beads in the sulfonic acid form (1) were obtained from Aldrich Chemical Company and were crushed at -150°C to give a course white powder. The sulfonic acid resin (1) was treated with phosphorous pentachloride for 24h at 80°C to give the sulfonyl chloride (2), see Scheme 1.
  • ester group was cleaved first in aqueous sodium hydroxide (to give the sodium salt of acid (6) as determined by the IR spectrum) and in the presence of n-butyl lithium as expected, the sulfonamide linkage remained intact for considerable periods and for up to several days in the absence of a proton source.
  • the functionalised radio-labelled sulphonamide resin (5) was refluxed for two hours in toluene and the potential dissolution of the material was monitored by removing aliquots of the solvent for scintillation counting.
  • the sulphonamide showed remarkable stability and none of the resin dissolved.
  • the Merrifield resin shed some of its mass and polypropylene completely dissolved within several minutes under similar conditions.
  • the sulfonyl chloride (2) was also converted to its N- sulfonyl (2S)-alanine t-butyl ester derivative (7) as was confirmed by its infrared (IR) spectrum.
  • IR infrared
  • the t- butyl ester was removed under acidic conditions to give the free acid (which showed the loss of carbonyl ester IR stretch) and this material was activated using standard peptide chemistry protocols and then treated with 1 C-labelled glycine methyl ester (labelled 1 uniformly in glycine moiety) .
  • activated derivatives of compound (11) could be reacted with a wide range of oxygen-, sulphur-, nitrogen- or phosphorus- centred nucleophiles, as was expected.
  • the thioether could be oxidised to the sulfone using the same range of oxidants that are used for solution phase chemistry.
  • the 3-fluorophenyl ether derivative displaced a new signal in the 19 F-NMR spectrum well separated from the aliphatic fluorine signals due to the polymer backbone.
  • phosphine oxide system is chiral at the P-atom and, therefore, the system could be elaborated to provide a chiral resin for the asymmetric synthesis of amines .
  • the principle has been demonstrated in solution phase chemistry and has been described in the literature and is within the capabilities of one skilled in the art.
  • the resulting resin- bound tertiary amine could be quarternised on nitrogen with common alkylating agents and could be eliminated from the resin to give a new tertiary amine and to regenerate the resin-bound vinyl sulfone (13) which could be used in further reaction cycles.
  • This type of system is referred to as a traceless linker connection because the product tertiary amine contains no trace of its synthetic origin.
  • any stable and unhindered connection between the N-atom of the sulfonamide and the C-atom which bears the vinyl sulfonyl group, whether it be aryl, benzylic or aliphatic, or even an N-atom in certain cases, would allow the system to function in the required manner.
  • any stable and unhindered connection between any stable fluoropolymer, whether its side-chains are perfluorinated or not, and the C-atom which bears the vinyl sulfonyl group, whether it be aryl, benzylic or aliphatic, or even an N-atom in certain cases would allow the system to function in the required manner.
  • any stable and unhindered connection between any stable fluoropolymer, whether its side- chains are perfluorinated or not, and the C-atoms which bear the functional group heteroatoms mentioned above for example the alcohol, ether or ester bearing C-atom in resins possessing a terminal OH or OR or OAr or 0- acyl, ureathane or other carbon acid or heteroatom acid ester group; the carbonyl C-atom in aldehyde, ketone, carboxylic acid, carboxylic ester and carboxamide derivatives, however substituted; the amino bearing C- atom in resins possessing terminal amino or amide groups, however substituted and including hydrazines and hydroxylamines ; the C-atom bearing the thiol or thioether functionality in thiol and thioether containing resins, the C-atom bearing the phosphorus atom in phosphine and phosphine oxide and phosphonate containing resins, however substituted, and the C-atoms which
  • bis- and tris- functionalised materials could be produced from a single fluoropolymer side chain to increase the loading capacity of the resins.
  • reaction of the resin sulfonyl chloride with tris- (hydroxymethyl)aminomethane or similar amines would give a derivatives of the type; fluoropolymer-S0 2 -NH- C(CH 2 OH) 3 which potentially could be further functionalised through each of the OH groups.
  • the unfunctionalised crushed resin starting material eg Nafion
  • the methyl ester derivative could be formed into shapes including shapes analogous to those corresponding to POSAM 8 microreactors (type B microreactors) by compression at 140-240°C in a mould.
  • the moulded shapes were chemically treated in several instances with the reagents and under the conditions outlined above to give functionalised type B microreactors resin shapes. These showed similar chemical loading properties to the non-compressed crushed resin and could be used for organic synthesis in open vessels.
  • the principle of using macroscopic functionalised frit resin blocks in solid- phase synthesis is established.
  • ⁇ spectra were referenced internally on 2 HOH ( ⁇ 4.68 ppm) and CHC1 3 ( ⁇ 7.27 ppm). Infra-red spectra were recorded on a Perkin-Elmer 1710 FT-IR spectrometer or a Nicolet InspectIR FT- IR using silicon ATR crystal. The samples were prepared as KBr discs or single beads. The frequencies ( ⁇ ) as absorption maxima are given in wavenumbers (cm -1 ) relative to a polystyrene standard. Microanalyses were determined in the microanalytical laboratory at the University of St Andrews. Mass spectra and accurate mass (HRMS) measurements were recorded in St Andrews on a VG 70-250 SE. Melting points were determined on either a Reichert hot stage ( ⁇ 230 °C) or an Electrothermal (>230 °C) apparatus and are uncorrected.
  • Reagents were used without purification unless otherwise stated. Quantities of reagents were calculated from the manufacturers' stated purities. Experiments were conducted at room temperature (20-25 °C) unless otherwise stated. All reactions that employed organometallic regents or other moisture sensitive reagents were performed in dry solvent under an atmosphere of dry nitrogen or argon in oven-dried and/or flame-dried glassware. Solutions in organic solvents were dried over anhydrous magnesium sulfate and concentrated or evaporated under reduced pressure on a B ⁇ chi rotary evaporator unless otherwise stated.
  • the solvents used were either distilled or of analar quality and were dried according to literature procedures: ethanol and methanol were dried over magnesium turnings; dichloromethane, DMF, pyridine and triethylamine were distilled over calcium hydride; THF and diethylether (referred to as ether) were dried over sodium and benzophenone. Thionyl chloride was distilled over sulphur, and the initials fractions were always discarded. All other chemicals were of analytical grade or were recrystallised or distilled before use.
  • Nafion beads [Nafion® NR50; 10-35 Mesh, hydrogen ion form, Eqiv. wt .1250 (max.), ion- exchange capacity 0.8meq/g] (1 g, 0.8 mmol) were crushed at -150 °C to give a course white powder. Dry toluene (20 cm 3 ) and phosphorous pentachloride (4.16 g, 20 mmol) were added and the mixture refluxed for 24 h. The resulting mixture was cooled and then filtered, before the filterate was washed with cuprous amount of dry dichloromethane. The slightly brown solid was then dried under reduced pressure at 60 °C to give the Nafion chloride in quantitative recovery (base on weight). DATA: ⁇ max (single beadyc ⁇ r 1 1270 and 1185 (SO 2 ) and 1050 (SO 2 Cl).
  • F 2 C ⁇ ⁇ CF 2 -S- CI is abbreviated to Nafion-S- Cl
  • DATA ⁇ max (single beadyc ⁇ r 1 1510 and 1480 (CH 2 ), 1320 (sulfonamide), 1220 and 1150
  • DATA ⁇ max (single beadyc ⁇ r 1 1510 and 1480 (CH 2 ), 1320 (sulfonamide), 1220 and 1150
  • DATA ⁇ max (single beadyc ⁇ r 1 1510 and 1480 (CH 2 ), 1320 (sulfonamide), 1220 and 1150
  • the resin was re suspended in DCM (7 cm 3 ) and then IDEA (0.6 cm 3 , 3.4 mmol) was added.

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Abstract

L'invention concerne une résine de polytétrafluoroéthylène supportant un groupe fonctionnel réactif. Cette résine comprend une chaîne latérale comportant une fraction de sulfonamide ou de sulfonanilimide comme dans la formule (I). Dans cette dernière, n et m sont chacun des nombres entiers compris entre 1 et plusieurs centaines; m est un groupe espaceur; Y est un groupe espaceur; Rc est un groupe d'hydrocarbure aliphatique C¿1-6? linéaire ou ramifié, éventuellement interrompu par des hétéroatomes; R?d¿ est un groupe aryle, substitué par une fraction fonctionnelle réactive comme un groupe carboxy, un groupe carboxyle, un groupe sulfonyle, amine, amide, thioester ou similaire. Cette résine est particulièrement utile dans la synthèse en phase solide et dans la fabrication des microréacteurs.
PCT/GB1998/002263 1997-08-05 1998-08-05 Resines perfluorees utilisees comme supports des reactions en phase solide Ceased WO1999007750A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU86356/98A AU8635698A (en) 1997-08-05 1998-08-06 Perfluorinated resins as a support for solid phase reactions

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GBGB9716454.5A GB9716454D0 (en) 1997-08-05 1997-08-05 Polymer
GB9716454.5 1997-08-05

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002094776A3 (fr) * 2001-05-24 2003-03-06 Linden Technologies Inc Surfaces de fixation covalente de ligands
EP1352243A4 (fr) * 2001-01-12 2008-07-02 Ge Healthcare Ltd Halogenures de perfluorosulfonyle et especes apparentees utilises comme modificateurs de support de polymere
EP1648194A4 (fr) * 2003-07-22 2009-09-09 Toho Kasei Co Ltd Materiau pour electret resistant a la chaleur et electret associe
CN102834374A (zh) * 2010-04-16 2012-12-19 3M创新有限公司 质子传导材料
CN110791139A (zh) * 2019-10-30 2020-02-14 阜阳市诗雅涤新材料科技有限公司 一种特种透明固体流平剂及其连续合成方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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DE3200822A1 (de) * 1982-01-14 1983-07-21 Lebrecht von Dr. 2406 Stockelsdorf Klitzing Verfahren zur kopplung von proteinen und haptenen an teflon(pfeil hoch)r(pfeil hoch) fuer immunologische und enzymatische bestimmungen
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EP1352243A4 (fr) * 2001-01-12 2008-07-02 Ge Healthcare Ltd Halogenures de perfluorosulfonyle et especes apparentees utilises comme modificateurs de support de polymere
WO2002094776A3 (fr) * 2001-05-24 2003-03-06 Linden Technologies Inc Surfaces de fixation covalente de ligands
EP1648194A4 (fr) * 2003-07-22 2009-09-09 Toho Kasei Co Ltd Materiau pour electret resistant a la chaleur et electret associe
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EP2558442A4 (fr) * 2010-04-16 2014-04-30 3M Innovative Properties Co Matériaux conducteurs de protons
US9419300B2 (en) 2010-04-16 2016-08-16 3M Innovative Properties Company Proton conducting materials
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