CN116924956A - 蒽光二聚体衍生物、其制备、手性胺基蒽光二聚体衍生物、其制备及应用 - Google Patents
蒽光二聚体衍生物、其制备、手性胺基蒽光二聚体衍生物、其制备及应用 Download PDFInfo
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- CN116924956A CN116924956A CN202210338438.5A CN202210338438A CN116924956A CN 116924956 A CN116924956 A CN 116924956A CN 202210338438 A CN202210338438 A CN 202210338438A CN 116924956 A CN116924956 A CN 116924956A
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- photodimer
- anthracene
- derivative
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- JUTIJVADGQDBGY-UHFFFAOYSA-N anthracene photodimer Chemical class C12=CC=CC=C2C2C(C3=CC=CC=C33)C4=CC=CC=C4C3C1C1=CC=CC=C12 JUTIJVADGQDBGY-UHFFFAOYSA-N 0.000 title claims abstract description 29
- YUENFNPLGJCNRB-UHFFFAOYSA-N anthracen-1-amine Chemical compound C1=CC=C2C=C3C(N)=CC=CC3=CC2=C1 YUENFNPLGJCNRB-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 13
- 125000006651 (C3-C20) cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 6
- 125000002252 acyl group Chemical group 0.000 claims abstract description 6
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 15
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical group CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims description 4
- 239000012069 chiral reagent Substances 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 238000006482 condensation reaction Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 230000003301 hydrolyzing effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 125000003118 aryl group Chemical group 0.000 description 21
- 239000007787 solid Substances 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- -1 1-dimethylpropyl Chemical group 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 239000003446 ligand Substances 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 229940125898 compound 5 Drugs 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 150000002430 hydrocarbons Chemical group 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- 125000002950 monocyclic group Chemical group 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 125000006708 (C5-C14) heteroaryl group Chemical group 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 229910052724 xenon Inorganic materials 0.000 description 2
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 2
- ZQEBQGAAWMOMAI-ZETCQYMHSA-N (2s)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound CC(C)(C)OC(=O)N1CCC[C@H]1C(O)=O ZQEBQGAAWMOMAI-ZETCQYMHSA-N 0.000 description 1
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- 125000006218 1-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 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 compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- XNNQFQFUQLJSQT-UHFFFAOYSA-N bromo(trichloro)methane Chemical compound ClC(Cl)(Cl)Br XNNQFQFUQLJSQT-UHFFFAOYSA-N 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
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 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 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
- 238000010511 deprotection reaction Methods 0.000 description 1
- 125000005046 dihydronaphthyl group Chemical group 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004146 energy storage Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005549 heteroarylene group Chemical group 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 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
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 238000011907 photodimerization Methods 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000005551 pyridylene group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 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
- 238000010898 silica gel chromatography Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000011232 storage material Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- UJJDEOLXODWCGK-UHFFFAOYSA-N tert-butyl carbonochloridate Chemical compound CC(C)(C)OC(Cl)=O UJJDEOLXODWCGK-UHFFFAOYSA-N 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
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000005556 thienylene group Chemical group 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
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- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
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- C07C311/19—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
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Abstract
本发明公开一种蒽光二聚体衍生物,其特征在于,具有如下互为非对映异构体的式I‑1、或I‑2所示的结构,其中,所述R1选自H、C1‑10烷基、C3‑20环烷基;M选自或R2、R3各自独立地选自H、C1‑10烷基、C3‑20环烷基;R4、R5各自独立地选自H、C1‑10烷基、C1‑20酰基、C1‑20磺酰基、C1‑C20苄基、C1‑C20烷氧基羰基;n选自1或2。其具有高效、快速且容易拆分制备得到手性胺基蒽光二聚体衍生物等特点。本发明还公开了该蒽光二聚体衍生物的制备、手性胺基蒽光二聚体衍生物、其制备及应用。
Description
技术领域
本发明涉及手性有机化合物技术领域。更具体地,涉及一种蒽光二聚体衍生物、其制备、手性胺基蒽光二聚体衍生物、其制备及应用。
背景技术
发展新型骨架结构的手性配体或催化剂对过渡金属催化的有机合成方法学的应用具有重要研究意义。因此使得设计与合成新骨架的配体的研究,成为近几十年来合成化学领域的前沿热点,并不断在催化领域的重要创新研究取得新进展。
蒽光二聚体独特的几何结构和X型骨架常常的被应用于主客体识别、分子开关和能量存储材料等领域,并且以蒽光二聚体为核心骨架的手性单膦配体在钯催化的不对称反应中也取得系列重要进展。但其在有机合成中的应用目前仍十分有限,其主要的研究困难在于蒽光二聚体的立体异构体的拆分和分离提纯,以及较差的溶解度等问题。目前获得其骨架的手性配体均为制备色谱拆分,使其合成成本过高,在一定程度上限制了应用。
发明内容
基于以上事实,本发明的目的在于提供一种蒽光二聚体衍生物、其制备、手性胺基蒽光二聚体衍生物、其制备及应用。该蒽光二聚体衍生物具有高效、快速且容易拆分制备得到手性胺基蒽光二聚体衍生物等特点,同时,该拆分的成本低,方法简单。
一方面,本发明提供一种蒽光二聚体衍生物,其具有如下互为非对映异构体的式I-1、或I-2所示的结构:
其中,
所述R1选自H、C1-10烷基、C3-20环烷基;
M选自
R2、R3各自独立地选自H、C1-10烷基、C3-20环烷基;
R4、R5各自独立地选自H、C1-10烷基、C1-20酰基、C1-20磺酰基、C1-C20苄基、C1-C20烷氧基羰基;
n选自1或2。
进一步地,上述技术方案中,包含式I-1、或I-2所示的结构的对映异构体、消旋体或非对映异构体。
又一方面,本发明提供一种蒽光二聚体衍生物的制备方法,该方法包括如下步骤:
将式II所示化合物与式III-1所示化合物/>或式III-2所示化合物/>发生缩合反应,
得到式IV-1所示化合物或式IV-2所示化合物/>
将式IV-1所示化合物或式IV-2所示化合物与式V所示化合物与蒽发生[4+4]光反应,得到具有互为非对映异构体的式I-1、或I-2所示的结构的所述蒽光二聚体衍生物;
其中,所述R1、R2、R3、R4、R5及n的定义如上所示。
上述制备方法中,制备得到的产物为互为非对映异构体的式I-1、或I-2所示的结构的所述蒽光二聚体衍生物。也即,产物中同时含有互为非对应异构体的两种产物,式I-1和式I-2所示结构的物质的混合。
上述制备方法中,通过对式III-1所示化合物或式III-2所示化合物具体选择的改变,从而实现对得到的产物中式I-1和式I-2所示结构的物质的比例的调节。调节范围可在质量比0.01:99.99-99.99:0.01之间,优选质量比在0.1:99.9-99.9:0.1。从而克服了现有技术的方法中,只能生成确定的50:50质量比的两种产物,而无法进行调控的问题。
如需将两种物质进一步分离,可通过柱层析或重结晶的方式进行分离,在此不赘述。
又一方面,本发明提供一种手性胺基蒽光二聚体衍生物,其由如上所述的蒽光二聚体衍生物水解得到,该手性胺基蒽光体二聚衍生物具有如下式VI所示的结构:
其中,
Q1为NR1H,R1选自H、C1-10烷基、C3-20环烷基。
本发明中提供的手性胺基蒽光二聚体衍生物具有X型立体结构。
又一方面,本发明提供如上所述的手性胺基蒽光二聚体衍生物的制备方法,该方法包括如下步骤:
将所述蒽光二聚体衍生物进行水解,得到所述手性胺基蒽光二聚体衍生物。
进一步地,该方法具体包括如下步骤:
在强碱条件下,于溶剂中回流反应,得到所述手性胺基蒽光二聚体衍生物。
进一步地,所述强碱选自叔丁醇钠;所述溶剂选自正丁醇和二甲基亚砜。
又一方面,本发明提供如上所述的手性胺基蒽光二聚体衍生物在制备手性试剂或手性药物中间体中的应用。
进一步地,将所述手性胺基蒽光二聚体衍生物用于制备其它蒽光二聚衍生的平面手性配体或催化剂。
本发明中,蒽光二聚体衍生物的制备方法中,方法采用化学拆分法生成非对映异构体的方式,即蒽光二聚体衍生物与手性试剂作用,化学转变为一对非对映异构体,即制备得到蒽光二聚体衍生物;再利用其极性不同或溶解度差异将其分离,最后通过去保护的手段(水解)以获取对映体纯的手性胺基蒽光二聚体衍生物。
除非另有说明,本申请中基团的上标为基团标记,下标一般指该基团的个数。
“任选……取代”为被任意取代基取代或未取代。
本发明单独使用或用作后缀或前缀的“C1-10烷基”意指支链和直链饱和脂族烃基,其具有1至10个碳原子(或若提供了碳原子的具体数目,则指该具体数目)的支链和直链饱和脂族烃基。例如,所述烷基可以为C1-6烷基,所述“C1-6烷基”表示具有1、2、3、4、5、6个碳原子的烷基。烷基的实例包括但不限于甲基、乙基、丙基、丁基、戊基、己基、异丙基、异丁基、仲丁基、叔丁基、异戊基、2-甲基丁基、1-甲基丁基、1-乙基丙基、1,2-二甲基丙基、新戊基、1,1-二甲基丙基、4-甲基戊基、3-甲基戊基、2-甲基戊基、1-甲基戊基、2-乙基丁基、1-乙基丁基、3,3-二甲基丁基、2,2-二甲基丁基、1,1-二甲基丁基、2,3-二甲基丁基、1,3-二甲基丁基、1,2-二甲基丁基、2-乙基己基、3-乙基己基、2-己基癸基等,以及上述基团的全部异构形式。
本发明使用的术语“C3-20环烷基”意指饱和的烃环,其可包括稠合或桥接的多环***。环烷基在其环结构中优选具有3至20个碳原子。优选地,环烷基在其环结构中具有3、4、5或6个碳原子。例如,“C3-6环烷基”表示例如环丙基、环丁基、环戊基或环己基的基团。
本发明使用的术语“3-20元杂环基”指包含3至20个原子的饱和、不饱和或部分饱和的单环、二环或三环(除非另有说明),其中1、2、3、4或5个环原子选自氮、硫或氧,除非另有说明,其可通过碳或氮来连接,其中-CH2-基团任选被-C(O)-代替;及其中除非另有相反说明,环氮原子或环硫原子任选被氧化以形成N-氧化物或S-氧化物或环氮原子任选被季铵化;其中环中的-NH任选被乙酰基、甲酰基、甲基或甲磺酰基取代;及环任选被一个或多个卤素取代。应该理解的是,当杂环基中S原子和O原子的总数超过1时,这些杂原子不彼此相邻。若所述杂环基为二环或三环。
术语“C6-20芳基”应理解为表示具有6~20个碳原子的一价芳香性或部分芳香性的单环、双环或三环烃环,优选“C6-14芳基”。术语“C6-14芳基”应理解为优选表示具有6、7、8、9、10、11、12、13或14个碳原子的一价芳香性或部分芳香性的单环、双环或三环烃环(“C6-14芳基”),特别是具有6个碳原子的环(“C6芳基”),例如苯基;或联苯基,或者是具有9个碳原子的环(“C9芳基”),例如茚满基或茚基,或者是具有10个碳原子的环(“C10芳基”),例如四氢化萘基、二氢萘基或萘基,或者是具有13个碳原子的环(“C13芳基”),例如芴基,或者是具有14个碳原子的环(“C14芳基”),例如蒽基。
术语“5-20元杂芳基”应理解为包括这样的一价单环、双环或三环芳族环系:其具有5~20个环原子且包含1-5个独立选自N、O和S的杂原子,例如“5-14元杂芳基”。术语“5-14元杂芳基”应理解为包括这样的一价单环、双环或三环芳族环系:其具有5、6、7、8、9、10、11、12、13或14个环原子,特别是5或6或9或10个碳原子,且其包含1-5个,优选1-3个独立选自N、O和S的杂原子并且,另外在每一种情况下可为苯并稠合的。特别地,杂芳基选自噻吩基、呋喃基、吡咯基、噁唑基、噻唑基、咪唑基、吡唑基、异噁唑基、异噻唑基、噁二唑基、***基、噻二唑基、噻-4H-吡唑基等以及它们的苯并衍生物,例如苯并呋喃基、苯并噻吩基、苯并噁唑基、苯并异噁唑基、苯并咪唑基、苯并***基、吲唑基、吲哚基、异吲哚基等;或吡啶基、哒嗪基、嘧啶基、吡嗪基、三嗪基等,以及它们的苯并衍生物,例如喹啉基、喹唑啉基、异喹啉基等;或吖辛因基、吲嗪基、嘌呤基等以及它们的苯并衍生物;或噌啉基、酞嗪基、喹唑啉基、喹喔啉基、萘啶基、蝶啶基、咔唑基、吖啶基、吩嗪基、吩噻嗪基、吩噁嗪基等。
术语“C1-20酰基”应理解为具有酰基结构的另一端连接有C1-19的烷基、环烷基、芳基、杂芳基的单元。优选地,比如苯二甲酰基、乙酰基等。
术语“C1-20磺酰基”应理解为具有磺酰基结构的另一端连接有C1-20的烷基、环烷基、芳基、杂芳基的单元。优选地,比如对甲苯磺酰基等。
术语“C1-C20苄基”应理解为具有苄基各种取代芳基结构的苄基。优选地,比如苄基、对甲氧基苄基等。在本发明中,芳基包含取代和未取代的芳基,其中取代是指基团上的一个或多个氢原子被选自下组的取代基取代:C1-C4烷基、C3-C10环烷基、卤素、羟基、羧基、醛基、酰基、胺基。代表性的芳基包括带有给电子和/或吸电子取代基芳基,如对甲苯基、对甲氧基苯基、五氟苯基等。
术语“C1-20烷氧基羰基”应理解为具有烷氧基羰基结构的另一端连接有C1-19的烷基、环烷基、芳基、杂芳基的单元。优选地,比如叔丁氧羰基、苄氧羰基、笏甲氧羰基等。
除非另有说明,杂环基、杂芳基或亚杂芳基包括其所有可能的异构形式,例如其位置异构体。因此,对于一些说明性的非限制性实例,吡啶基或亚吡啶基包括吡啶-2-基、亚吡啶-2-基、吡啶-3-基、亚吡啶-3-基、吡啶-4-基和亚吡啶-4-基;噻吩基或亚噻吩基包括噻吩-2-基、亚噻吩-2-基、噻吩-3-基和亚噻吩-3-基。
本发明中,当所述结构具有手性时,除非明确说明是光学纯外,所涉及的化合物以及所画结构均指外消旋物,或者手性异构体的混合物。
本发明的有益效果如下:
本发明提供的蒽光二聚体衍生物因其独特的结构使得其具有更容易拆分成手性胺基蒽光二聚体衍生物(现有技术中获得手性胺基蒽光二聚体的方法需要使用制备型手性液相色谱进行分离,成本高)的特点。本发明的制备方法中,以廉价易得商业可用的起始原料和手性拆分试剂,快速地开发了一条制备蒽光二聚体衍生物以及采用该手性蒽光二聚体衍生物制备得到手性胺基蒽光二聚体衍生物的新路径。利用此平面手性的胺基蒽光二聚体衍生物,并结合其独特的立体骨架,可设计与合成出新型平面手性配体或催化剂。这将有助于开发更加友好、更加原子经济性的反应新体系,对社会发展具有重大的研究意义。
附图说明
下面结合附图对本发明的具体实施方式作进一步详细的说明。
图1示出实施例1制备得到的黄色固体粉末3的核磁谱图。
图2示出实施例1制备得到的化合物4a的核磁谱图。
图3示出实施例1制备得到的化合物4b的核磁谱图。
图4示出实施例2中制备得到的化合物(Sp)-5的HPLC分析结果谱图。
图5示出实施例2制备得到的化合物(Sp)-5的核磁谱图。
图6示出实施例2中制备得到的化合物(Rp)-5的HPLC分析结果谱图。
图7示出实施例3制备得到的白色固体7的核磁谱图。
图8示出实施例3制备得到的化合物8a和8b混合物的核磁谱图。
图9示出实施例4制备得到的化合物5的核磁谱图。
图10示出实施例5制备得到的化合物9的核磁谱图。
图11示出实施例6制备得到的化合物10的核磁谱图。
具体实施方式
为了更清楚地说明本发明,下面结合优选实施例和附图对本发明做进一步的说明。附图中相似的部件以相同的附图标记进行表示。本领域技术人员应当理解,下面所具体描述的内容是说明性的而非限制性的,不应以此限制本发明的保护范围。
以下,对各实施例中需要用到的原料进行如下说明:
实施例1:
茄形瓶中称取Boc-L-脯氨酸2(6.70g,31.0mmol,1.5equiv),加入二氯甲烷(62mL)进行溶解。在0℃下依次加入氯甲酸叔丁酯(4.20g,31.0mmol,1.5equiv)和三乙胺(3.10g,31.0mmol,1.5equiv),在0℃下搅拌20分钟。在0℃下加入1-氨基蒽1(4.00g,20.7mmol,1.0equiv)到该反应混合物中,搅拌1-2分钟后将反应恢复室温,搅拌10小时。将反应液转移到分液漏斗,依次加入饱和碳酸氢钠溶液、饱和氯化铵溶液洗涤,水相用二氯甲烷萃取3次。合并有机相,用无水硫酸钠干燥,减压除去溶剂,得到粗产物。用石油醚对该粗产物进行重结晶,得到黄白色固体粉末3(7.82g,97%产率)。
1H NMR(400MHz,Chloroform-d)δ10.10(s,1H),8.75(s,1H),8.44(s,1H),8.28(s,1H),8.10–7.95(m,2H),7.84–7.67(m,1H),7.55–7.43(m,3H),4.76–4.64(m,1H),3.59–3.40(m,2H),2.78–2.65(m,1H),2.26–1.91(m,3H),1.68(s,9H).具体核磁谱图如图1所示。
在充满氮气的手套箱中,将蒽(2.30g,12.8mmol,10.0equiv),化合物3(500mg,1.28mmol,1.0equiv)和脱气的甲苯(102mL)加入到厚壁耐压瓶中。将瓶盖拧紧,移出手套箱,在氙灯光源照射下室温搅拌24小时,混合物用硅藻土过滤,随后通过柱层析和重结晶分离得白色固体化合物4a(309mg,42%收率,98%纯度)和白色固体化合物4b(202mg,28%收率,96%纯度)。固体化合物4a和固体化合物4b容易进一步分离。
化合物4a:
1H NMR(400MHz,Chloroform-d)δ9.44(s,1H),7.48(s,1H),7.20(s,1H),6.93–6.74(m,13H),4.89–4.76(m,1H),4.71–4.54(m,4H),3.56–3.39(m,2H),2.75–2.62(m,1H),2.10–1.88(m,3H),1.78(s,9H).化合物4a的核磁谱图如图2所示。
化合物4b:
1H NMR(400MHz,Chloroform-d)δ9.10(s,1H),7.32(s,1H),7.01(s,1H),6.94–6.75(m,13H),4.89–4.76(m,1H),4.67–4.53(m,4H),3.65–3.44(m,2H),2.70–2.50(m,1H),2.12–1.90(m,3H),1.71(s,9H).化合物4b的核磁谱图如图3所示。
采用类似如上所述的方法用一些环状手性氨基酸生成制备如下表1所示的一些蒽光二聚体衍生物非对映异构体,其质量比也如下表1所示。
表1
实施例2
茄形瓶中加入4a(250mg,0.44mmol,1.0equiv),叔丁醇钠(861.6mg,8.79mmol,20.0equiv),正丁醇(40mL)和二甲基亚砜(2.35mL),在回流的条件下剧烈搅拌反应24h。在减压移除溶剂后,用少量二氯甲烷溶解瓶中残留固体将其倒入干净的分液漏斗,随后加入2M盐酸萃取,水相用二氯甲烷萃取三次,合并有机相,无水硫酸钠干燥,浓缩。残余固体在石油醚的条件下进行重结晶得黄色粉末(146mg,89%产率,99%纯度)。
使用Daicel AS柱的HPLC分析确定对映体(分析条件:正己烷/i-PrOH=95:5)。结果如图4所示。
1H NMR(400MHz,Chloroform-d)δ7.09(s,1H),6.98–6.78(m,11H),6.67–6.61(t,J=7.5Hz,1H),6.50–6.45(d,J=7.0Hz,1H),6.23–6.18(d,J=8.1Hz,1H),4.59–4.49(m,4H),3.58(s,2H).得到的(Sp)-5的核磁谱图如图5所示。
根据上述制备(Sp)-5的方法,水解4b(150mg,0.26mmol)得到黄色粉末(Rp)-5(84mg,86%产率,97%纯度)。
使用Daicel AS柱的HPLC分析确定对映体(分析条件:正己烷/i-PrOH=95:5),结果如图6所示。
1H NMR(400MHz,Chloroform-d)同上。
实施例3
茄形瓶中加入6(636mg,2.4mmol,1.2equiv),1-氨基蒽1(386mg,2.0mmol,1.0equiv),1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(460mg,2.2mmol,1.1equiv),1-羟基苯并***(460mg,2.2mmol,1.1equiv),在室温下搅拌24小时。将反应液转移到分液漏斗,加入少量水萃取,水相用二氯甲烷萃取3次。合并有机相,用无水硫酸钠干燥,减压除去溶剂,得到粗产物。粗产物用柱层析方法进一步纯化得到白色固体7(312mg,35%产率)。
1H NMR(400MHz,Chloroform-d)δ8.74(s,1H),8.49(s,1H),8.43(s,1H),8.02–7.96(m,3H),7.86–7.81(d,J=8.6Hz,1H),7.52–7.30(m,7H),5.38–5.27(m,1H),5.27–5.21(m,2H),4.61–4.51(m,1H),2.03–1.92(m,1H),1.91–1.81(m,1H),1.77–1.68(m,1H),1.08–1.01(m,6H).白色固体7的核磁谱图如图7所示。
在充满氮气的手套箱中,将蒽(1.78g,10.0mmol,10.0equiv),化合物7(440mg,1.0mmol,1.0equiv)和脱气的甲苯(68mL)加入到厚壁耐压瓶中。将瓶盖拧紧,移出手套箱,在氙灯光源照射下室温搅拌24小时,混合物用硅藻土过滤,随后通过柱层析分离得白色固体8a和8b的混合物(327mg,53%总产率)。8a和8b较难继续分离。
1H NMR(400MHz,Chloroform-d)δ8.23–8.00(m,1H),7.50–7.28(m,6H),7.23–7.14(m,1H),7.12–6.99(m,1H),6.97–6.88(m,5H),6.86–6.77(m,7H),5.42–5.18(m,3H),4.77–4.49(m,4H),4.46–4.37(m,1H),1.98–1.89(m,1H),1.88–1.78(m,1H),1.73–1.64(m,1H),1.59–1.55(m,1H),1.10–1.00(m,6H).其核磁谱图如图8所示。
采用类似如上所述的方法用一些开链手性氨基酸生成制备如下表2所示的一些蒽光二聚体衍生物非对映异构体,其质量比也如下表2所示。
表2
实施例4
茄形瓶中加入8(61.8mg,0.10mmol,1.0equiv),浓盐酸(1mL)和乙醇(2mL),在80℃加热的条件下剧烈搅拌反应12h。待反应结束,NaOH中和该反应液,水相用二氯甲烷萃取三次,合并有机相,在减压移除溶剂后,通过柱层析分离得目标产物(27mg,36%产率)。
1H NMR(400MHz,Chloroform-d)δ7.09(s,1H),6.98–6.78(m,11H),6.67–6.61(t,J=7.5Hz,1H),6.50–6.45(d,J=7.0Hz,1H),6.23–6.18(d,J=8.1Hz,1H),4.59–4.49(m,4H),3.58(s,2H).化合物5的核磁谱图如图9所示。
一些应用实施例:
实施例5
反应瓶中加入化合物5(100mg,0.27mmol,1.0equiv),亚硝酸钠(93mg,1.35mmol,5.0equiv),一溴三氯甲烷(107mg,0.54mmol,2.0equiv),二氯甲烷(5.0mL)和水(5.0ml),在室温下搅拌5分钟。随后加入乙酸(323mg,5.38mmol,20.0equiv),将该反应在室温下搅拌1小时。将反应液倒入分液漏斗,水相用二氯甲烷萃取3次,合并有机相,用饱和食盐水洗,无水硫酸钠干燥,减压下移除溶剂。粗产物用柱层析方法进一步纯化得到白色固体9(77.4mg,66%产率)。
从依据本方法拆分后的化合物5出发,可以得到光学纯的化合物9,化合物9的核磁谱图如图10所示。进而可根据参考文献(Org.Lett.2019,21,8158)制备光学纯的单膦配体diAnthPhos。
1H NMR(400MHz,Chloroform-d)δ7.18-7.16(m,1H),7.01(dd,J=8.0Hz,1.1Hz,1H),6.97-6.78(m,12H),6.66(dd,J=7.7Hz,7.7Hz,1H),5.06(d,J=11.0Hz,1H),4.59(d,J=11.1Hz,1H),4.55-4.51(m,2H).
实施例6
在空气中,化合物5(104mg,0.28mmol),浓硫酸(2.0mL)和醋酸(4.0mL)分别加入到40mL反应瓶中,于0℃搅拌5分钟。随后在0℃下10分钟内加入亚硝酸钠的水溶液(38mg,0.58mmol,2.0equiv,2.0mL H2O)反应1小时。最后再将B2Pin2(142mg,0.58mmol,2.0equiv,2.0mL H2O)缓慢滴加到反应体系中,于0℃下反应1小时,随后升温至室温反应3小时。反应结束后,加入氢氧化钠水溶液淬灭反应,调节pH值至中性。然后用二氯甲烷萃取,浓缩。使用硅胶柱色谱法纯化,得到白色固体10(68mg,50%产率)。
从依据本方法拆分后的化合物5出发,可以得到光学纯的化合物10,化合物10的核磁谱图如图11所示。进而可根据参考文献(Org.Lett.2021,23,5485)制备光学纯单膦配体DapPhos。
1H NMR(400MHz,Chloroform-d)δ7.36(d,J=7.5Hz,1H),7.04-6.99(m,2H),6.98-6.94(m,4H),6.90(dd,J=6.3,2.5Hz,1H),6.88-6.77(m,7H),5.50(d,J=11.1Hz,1H),4.62(d,J=11.1Hz,1H),4.58-4.54(m,2H),1.48(d,J=3.4Hz,12H).
显然,本发明的上述实施例仅仅是为清楚地说明本发明所作的举例,而并非是对本发明的实施方式的限定,对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动,这里无法对所有的实施方式予以穷举,凡是属于本发明的技术方案所引伸出的显而易见的变化或变动仍处于本发明的保护范围之列。
Claims (8)
1.一种蒽光二聚体衍生物,其特征在于,具有如下互为非对映异构体的式I-1、或I-2所示的结构:
其中,
所述R1选自H、C1-10烷基、C3-20环烷基;
M选自
R2、R3各自独立地选自H、C1-10烷基、C3-20环烷基;
R4、R5各自独立地选自H、C1-10烷基、C1-20酰基、C1-20磺酰基、C1-C20苄基、C1-C20烷氧基羰基;
n选自1或2。
2.如权利要求1所述的蒽光二聚体衍生物的制备方法,其特征在于,包括如下步骤:
将式II所示化合物与式III-1所示化合物/>或式III-2所示化合物发生缩合反应,
得到式IV-1所示化合物或式IV-2所示化合物/>
将式IV-1所示化合物或式IV-2所示化合物与式V所示化合物与蒽发生[4+4]光反应,得到具有互为非对映异构体的式I-1、或I-2所示的结构的所述蒽光二聚体衍生物;
其中,所述R1、R2、R3、R4、R5及n的定义同权利要求1。
3.根据权利要求2所述的制备方法,其特征在于,所述制备方法制备得到的互为非对映异构体的式I-1、或I-2所示的结构的质量比为0.1:99.9-99.9:0.1。
4.一种手性胺基蒽光二聚体衍生物,其特征在于,由如权利要求1所述的蒽光二聚体衍生物水解得到,该手性胺基蒽光二聚体衍生物具有如下式VI所示的结构:
其中,
Q1为NR1H,R1选自H、C1-10烷基、C3-20环烷基。
5.如权利要求4所述的手性胺基蒽光二聚体衍生物的制备方法,其特征在于,包括如下步骤:
将所述蒽光二聚体衍生物进行水解,得到所述手性胺基蒽光二聚体衍生物。
6.根据权利要求5所述的制备方法,其特征在于,具体包括如下步骤:
在强碱条件下,于溶剂中回流反应,得到所述手性胺基蒽光二聚体衍生物。
7.根据权利要求6所述的制备方法,其特征在于,所述强碱选自叔丁醇钠;所述溶剂选自正丁醇和二甲基亚砜。
8.如权利要求4所述的手性胺基蒽光二聚体衍生物在制备手性试剂或手性药物中间体中的应用。
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