JP6047560B2 - デンドリマーとその調製方法 - Google Patents
デンドリマーとその調製方法 Download PDFInfo
- Publication number
- JP6047560B2 JP6047560B2 JP2014515829A JP2014515829A JP6047560B2 JP 6047560 B2 JP6047560 B2 JP 6047560B2 JP 2014515829 A JP2014515829 A JP 2014515829A JP 2014515829 A JP2014515829 A JP 2014515829A JP 6047560 B2 JP6047560 B2 JP 6047560B2
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- Prior art keywords
- dendrimer
- formula
- core
- compound
- alkyl
- Prior art date
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- 239000000412 dendrimer Substances 0.000 title claims description 76
- 229920000736 dendritic polymer Polymers 0.000 title claims description 76
- 238000000034 method Methods 0.000 title claims description 25
- 238000002360 preparation method Methods 0.000 title description 8
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 150000001875 compounds Chemical class 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- -1 amine compound Chemical class 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 12
- 150000002828 nitro derivatives Chemical class 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
- 150000002118 epoxides Chemical class 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 150000001412 amines Chemical class 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 16
- 239000010410 layer Substances 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- LIJYCZRLLFCTKM-UHFFFAOYSA-N 2-(2-methyl-2-nitropropyl)oxirane Chemical compound [O-][N+](=O)C(C)(C)CC1CO1 LIJYCZRLLFCTKM-UHFFFAOYSA-N 0.000 description 14
- 239000003054 catalyst Substances 0.000 description 13
- 125000003118 aryl group Chemical group 0.000 description 11
- 239000000178 monomer Substances 0.000 description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- 150000002924 oxiranes Chemical class 0.000 description 9
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 125000004971 nitroalkyl group Chemical group 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 125000001424 substituent group Chemical group 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 5
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 5
- 150000001336 alkenes Chemical class 0.000 description 5
- 238000006735 epoxidation reaction Methods 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical compound NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 238000012377 drug delivery Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 4
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003573 thiols Chemical group 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- NJWSNNWLBMSXQR-UHFFFAOYSA-N 2-hexyloxirane Chemical compound CCCCCCC1CO1 NJWSNNWLBMSXQR-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical group [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- 229920000305 Nylon 6,10 Polymers 0.000 description 3
- 239000007868 Raney catalyst Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 230000029936 alkylation Effects 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 238000009295 crossflow filtration Methods 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000004817 gas chromatography Methods 0.000 description 3
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 238000003828 vacuum filtration Methods 0.000 description 3
- WLXRLSSQDDQKRI-UHFFFAOYSA-N 4-amino-1-[(4-amino-2-hydroxy-4-methylpentyl)-[6-[bis(4-amino-2-hydroxy-4-methylpentyl)amino]hexyl]amino]-4-methylpentan-2-ol Chemical compound CC(C)(N)CC(O)CN(CC(O)CC(C)(C)N)CCCCCCN(CC(O)CC(C)(C)N)CC(O)CC(C)(C)N WLXRLSSQDDQKRI-UHFFFAOYSA-N 0.000 description 2
- SFRYSSACJAJJJI-UHFFFAOYSA-N 4-methyl-4-nitropent-1-ene Chemical compound [O-][N+](=O)C(C)(C)CC=C SFRYSSACJAJJJI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 238000006842 Henry reaction Methods 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 238000006683 Mannich reaction Methods 0.000 description 2
- 238000006957 Michael reaction Methods 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 150000001334 alicyclic compounds Chemical class 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000536 complexating effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000007306 functionalization reaction Methods 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 230000026030 halogenation Effects 0.000 description 2
- 238000005658 halogenation reaction Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- SFDJOSRHYKHMOK-UHFFFAOYSA-N nitramide Chemical compound N[N+]([O-])=O SFDJOSRHYKHMOK-UHFFFAOYSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 238000001890 transfection Methods 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- JSZOAYXJRCEYSX-UHFFFAOYSA-N 1-nitropropane Chemical compound CCC[N+]([O-])=O JSZOAYXJRCEYSX-UHFFFAOYSA-N 0.000 description 1
- MQCPOLNSJCWPGT-UHFFFAOYSA-N 2,2'-Bisphenol F Chemical compound OC1=CC=CC=C1CC1=CC=CC=C1O MQCPOLNSJCWPGT-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- VOXNHRYDHRSHOA-UHFFFAOYSA-N 2-(2-nitrobutyl)oxirane Chemical compound CCC([N+]([O-])=O)CC1CO1 VOXNHRYDHRSHOA-UHFFFAOYSA-N 0.000 description 1
- SFRDXVJWXWOTEW-UHFFFAOYSA-N 2-(hydroxymethyl)propane-1,3-diol Chemical compound OCC(CO)CO SFRDXVJWXWOTEW-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 1
- FGLBSLMDCBOPQK-UHFFFAOYSA-N 2-nitropropane Chemical compound CC(C)[N+]([O-])=O FGLBSLMDCBOPQK-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 1
- HXVLOFRKNSOPQD-HYXAFXHYSA-N CC(C)(/C=C1\OC1)[N+]([O-])=O Chemical compound CC(C)(/C=C1\OC1)[N+]([O-])=O HXVLOFRKNSOPQD-HYXAFXHYSA-N 0.000 description 1
- NRDQZVOSFXUNTC-UHFFFAOYSA-N CC(C)(CC1CCCCO1)[N+](=O)[O-] Chemical compound CC(C)(CC1CCCCO1)[N+](=O)[O-] NRDQZVOSFXUNTC-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 229920001503 Glucan Polymers 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical compound CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 238000005937 allylation reaction Methods 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 229940106691 bisphenol a Drugs 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000003700 epoxy group Chemical group 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 1
- NAQMVNRVTILPCV-BFGUONQLSA-N hexane-1,6-diamine Chemical group [15NH2]CCCCCC[15NH2] NAQMVNRVTILPCV-BFGUONQLSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- SENLDUJVTGGYIH-UHFFFAOYSA-N n-(2-aminoethyl)-3-[[3-(2-aminoethylamino)-3-oxopropyl]-[2-[bis[3-(2-aminoethylamino)-3-oxopropyl]amino]ethyl]amino]propanamide Chemical compound NCCNC(=O)CCN(CCC(=O)NCCN)CCN(CCC(=O)NCCN)CCC(=O)NCCN SENLDUJVTGGYIH-UHFFFAOYSA-N 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000000466 oxiranyl group Chemical group 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical compound [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 229920000083 poly(allylamine) Polymers 0.000 description 1
- 229920000962 poly(amidoamine) Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
Classifications
-
- 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
- C07C229/10—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 acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
- C07C229/16—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 acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids
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- C—CHEMISTRY; METALLURGY
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- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G83/00—Macromolecular compounds not provided for in groups C08G2/00 - C08G81/00
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- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
-
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C215/04—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated
- C07C215/06—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic
- C07C215/18—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being saturated and acyclic with hydroxy groups and at least two amino groups bound to the carbon skeleton
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
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- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/04—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring from cyclic ethers only
- C08G65/22—Cyclic ethers having at least one atom other than carbon and hydrogen outside the ring
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Description
本出願は、2011年6月16日に出願された仮出願番号第61/497,551号の優先権を主張するものであり、その全体が参照により本明細書に援用される。本発明は、概して、星状デンドリマー、及びエポキシ官能化ニトロアルカンから星状デンドリマーを調製する方法に関する。
2個以上の末端残基を含み、多価の有機分子に由来したコアと;
そのコアから径方向に放射する第1〜第8世代であって、
式(A):
前記内側世代の最も外側に結合した、又は前記内側世代が存在していない場合は前記末端残基を介して前記コアに結合した外側層であって、式(B):
を含む、デンドリマーが提供される。
(a)2個以上の末端残基を含む多価の有機分子を供給する工程と;
(b)式(III)のニトロアルキルオキシラン化合物:
(c)前記コアに結合された式(B−2):
(d)デンドリマーを得るために、工程(b)及び/又は(c)において多価の有機分子の代わりにアミン化合物を式(III)のニトロアルキルオキシラン化合物と反応させる操作を、任意に1〜7回繰り返す工程と、
を含む方法が提供される。
第2世代アミンデンドリマー
上記工程Cに記載したものと本質的に同じ手順に従って、1モルの化合物(4)を8モルのオキシラン(2)と反応させた。
トリス(アミノエチル)アミンによる第1世代の調製
トリス(アミノエチル)アミンによる第2世代の調製
トリス(2−アミノエチル)アミンからのプロピオン酸メチルデンドリマーの調製
エポキシオクタンとの反応によって疎水性にされた第2世代のデンドリマーの調製
トリス(2−アミノエチルアミン)に由来する2.5g(0.001モル)の第2世代のデンドリマー(実施例3)を25mlのメタノールに溶かした溶液に、3.15gのエポキシオクタン(0.027モル)を添加し、この反応物を室温で約6日間撹拌した。エポキシオクタンの消費はGCによってモニタすることができ、所望により、60℃に加熱して反応を加速することができる。ロータリー・エバポレータによって溶媒を除去すると、粗生成物が得られた。その粗生成物は、公知の技術によってさらに精製することができる。
[1]2個以上の末端残基を含み、多価の有機分子に由来したコアと;
そのコアから径方向に放射する第1〜第8世代であって、式(A):
前記内側世代の最も外側に結合した、又は前記内側世代が存在していない場合は前記末端残基を介して前記コアに結合した外側層であって、式(B):
を含む、デンドリマー。
[2]前記末端残基が、アミン残基、ヒドロキシル残基、チオール残基、又はこれらの2個以上の組み合わせである、[1]に記載のデンドリマー。
[3]R 1 とR 2 が、それぞれC 1 〜C 10 のアルキルである、[1]又は[2]に記載のデンドリマー。
[4]R 3 がHである、[1]〜[3]のいずれか一項に記載のデンドリマー。
[5]前記コアが、2個のアミン残基を含む脂肪族非環式残基であるとき、少なくとも2個の世代を含む、[1]〜[4]のいずれか一項に記載のデンドリマー。
[6]表1に示された構造を有する、[1]のデンドリマー。
[7][1]のデンドリマーを製造する方法であって、
(a)2個以上の末端残基を含む多価の有機分子を供給する工程と;
(b)式(III)のニトロアルキルオキシラン化合物:
(c)前記コアに結合された式(B−2):
(d)デンドリマーを得るために、工程(b)及び/又は(c)において多価の有機分子の代わりにアミン化合物を式(III)のニトロアルキルオキシラン化合物と反応させる操作を、任意に1〜7回繰り返す工程と、
を含む、前記方法。
[8]前記多価の有機分子の末端官能基が、アミン、ヒドロキシル、チオール、又はこれらの2種以上の組み合わせである、[7]に記載の方法。
[9]R 4 とR 5 が、これらが結合する窒素と共にNO 2 基を形成しており、前記デンドリマーを、塩基を触媒としてアルデヒドと反応させること(ヘンリー反応);塩基を触媒としてα,β−不飽和エステル又はニトリルと反応させること(マイケル反応);塩基を触媒としてアミンの存在下でアルデヒドと反応させること(マンニッヒ反応);強塩基を触媒としてハロゲン化アルキルと反応させること(アルキル化);強塩基を触媒として塩化アシル又は他の活性化されたエステルと反応させること(アクリル化);塩基を触媒としてハロゲン化することのいずれかによって、更に機能化し、機能化されたデンドリマーを形成する、[7]又は[8]に記載の方法。
[10]R 4 とR 5 がHであり、前記デンドリマーを、エポキシド、アクリレート、酸の塩化物のいずれかと反応させることによって、更に機能化し、機能化されたデンドリマーを形成する、[7]又は[8]に記載の方法。
[11]前記デンドリマーを、染料、薬、又は薬を標的とする分子のいずれかによって、更に機能化する、[9]又は[10]に記載の方法。
[12]前記機能化されたデンドリマーが、表2に示された構造を有する、[10]に記載の方法。
Claims (5)
- 2個以上の末端残基を含み、多価の有機分子に由来したコアと;
そのコアから径方向に放射する第1〜第8世代とを含むデンドリマーであって、
前記第1〜第8世代は、
式(A):
を独立に有する2個以上の分子単位を含む1〜7の内側世代であって、最も内側の内側世代がR3に結合した炭素で末端残基を介して前記コアに結合した、1〜7の内側世代と;
前記内側世代の最も外側に結合した外側層であって、式(B):
を独立に有する2個以上の分子単位を含む、前記外側層と、
を含む、デンドリマー。 - 請求項1または2に記載のデンドリマーを製造する方法であって、
(a)2個以上の末端残基を含む多価の有機分子を供給する工程と;
(b)式(III)のニトロアルキルオキシラン化合物:
(c)前記コアに結合された式(B−2):
(d)デンドリマーを得るために、工程(b)及び/又は(c)において多価の有機分子の代わりにアミン化合物を式(III)のニトロアルキルオキシラン化合物と反応させる操作を、任意に1〜7回繰り返す工程と、
を含む、前記方法。 - R4とR5がHであり、前記デンドリマーを、エポキシド、アクリレート、酸の塩化物のいずれかと反応させることによって、更に機能化し、機能化されたデンドリマーを形成する、請求項3に記載の方法。
- 前記デンドリマーを、染料、薬、又は薬を標的とする分子のいずれかによって、更に機能化する、請求項4に記載の方法。
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