CN113773294B - Preparation method and application of flavone and isoflavone compounds - Google Patents
Preparation method and application of flavone and isoflavone compounds Download PDFInfo
- Publication number
- CN113773294B CN113773294B CN202111095970.0A CN202111095970A CN113773294B CN 113773294 B CN113773294 B CN 113773294B CN 202111095970 A CN202111095970 A CN 202111095970A CN 113773294 B CN113773294 B CN 113773294B
- Authority
- CN
- China
- Prior art keywords
- nmr
- cdcl
- formula
- follows
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 21
- 150000002515 isoflavone derivatives Chemical class 0.000 title claims abstract description 14
- 229930003944 flavone Natural products 0.000 title description 4
- 235000011949 flavones Nutrition 0.000 title description 4
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 title description 3
- 150000002212 flavone derivatives Chemical class 0.000 title description 3
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 title description 3
- -1 isoflavone compound Chemical class 0.000 claims abstract description 39
- 229930003935 flavonoid Natural products 0.000 claims abstract description 33
- 235000017173 flavonoids Nutrition 0.000 claims abstract description 33
- 150000002215 flavonoids Chemical class 0.000 claims abstract description 31
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 26
- CJWQYWQDLBZGPD-UHFFFAOYSA-N isoflavone Natural products C1=C(OC)C(OC)=CC(OC)=C1C1=COC2=C(C=CC(C)(C)O3)C3=C(OC)C=C2C1=O CJWQYWQDLBZGPD-UHFFFAOYSA-N 0.000 claims abstract description 26
- 235000008696 isoflavones Nutrition 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 13
- 239000002904 solvent Substances 0.000 claims abstract description 12
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical group C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 claims abstract description 10
- 239000003446 ligand Substances 0.000 claims abstract description 10
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 9
- 239000012298 atmosphere Substances 0.000 claims abstract description 6
- 239000007858 starting material Substances 0.000 claims abstract description 6
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 239000003513 alkali Substances 0.000 claims abstract description 5
- 239000011261 inert gas Substances 0.000 claims abstract description 3
- 125000003518 norbornenyl group Chemical group C12(C=CC(CC1)C2)* 0.000 claims abstract 3
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 150000002148 esters Chemical class 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 10
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 229910052710 silicon Inorganic materials 0.000 claims description 8
- 239000010703 silicon Substances 0.000 claims description 8
- 125000003368 amide group Chemical group 0.000 claims description 7
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 claims description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 6
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- 235000011181 potassium carbonates Nutrition 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- IHMXVSZXHFTOFN-UHFFFAOYSA-N 2-ethyloxolane Chemical compound CCC1CCCO1 IHMXVSZXHFTOFN-UHFFFAOYSA-N 0.000 claims description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims description 2
- 150000001345 alkine derivatives Chemical class 0.000 claims description 2
- 150000001502 aryl halides Chemical group 0.000 claims description 2
- ZOAIGCHJWKDIPJ-UHFFFAOYSA-M caesium acetate Chemical compound [Cs+].CC([O-])=O ZOAIGCHJWKDIPJ-UHFFFAOYSA-M 0.000 claims description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 235000011056 potassium acetate Nutrition 0.000 claims description 2
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 2
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 2
- 239000011736 potassium bicarbonate Substances 0.000 claims description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 2
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 claims description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 claims description 2
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 239000011630 iodine Substances 0.000 claims 1
- 229910052740 iodine Inorganic materials 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 6
- JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 abstract description 4
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 238000009776 industrial production Methods 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 68
- 239000011734 sodium Substances 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 150000002848 norbornenes Chemical class 0.000 description 6
- 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 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000004440 column chromatography Methods 0.000 description 4
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical compound C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 229930013032 isoflavonoid Natural products 0.000 description 4
- 150000003817 isoflavonoid derivatives Chemical class 0.000 description 4
- 235000012891 isoflavonoids Nutrition 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- SZDBDDKQJHHRGH-UHFFFAOYSA-N 3-iodochromen-4-one Chemical compound C1=CC=C2C(=O)C(I)=COC2=C1 SZDBDDKQJHHRGH-UHFFFAOYSA-N 0.000 description 3
- BXCNVYATLWNXFK-UHFFFAOYSA-N C(=O)OCC.C12CCC(C=C1)C2 Chemical compound C(=O)OCC.C12CCC(C=C1)C2 BXCNVYATLWNXFK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- OTAFHZMPRISVEM-UHFFFAOYSA-N chromone Chemical group C1=CC=C2C(=O)C=COC2=C1 OTAFHZMPRISVEM-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- HDIWKNXVBQPJCO-UHFFFAOYSA-N ethyl 2-methylsulfanyl-6-oxo-1h-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)NC1=O HDIWKNXVBQPJCO-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- SWGQITQOBPXVRC-UHFFFAOYSA-N methyl 2-bromobenzoate Chemical compound COC(=O)C1=CC=CC=C1Br SWGQITQOBPXVRC-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- OMBVEVHRIQULKW-DNQXCXABSA-M (3r,5r)-7-[3-(4-fluorophenyl)-8-oxo-7-phenyl-1-propan-2-yl-5,6-dihydro-4h-pyrrolo[2,3-c]azepin-2-yl]-3,5-dihydroxyheptanoate Chemical compound O=C1C=2N(C(C)C)C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C(C=3C=CC(F)=CC=3)C=2CCCN1C1=CC=CC=C1 OMBVEVHRIQULKW-DNQXCXABSA-M 0.000 description 1
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
- MEYCYYFOVOERCT-UHFFFAOYSA-N 2-iodochromen-4-one Chemical class C1=CC=C2OC(I)=CC(=O)C2=C1 MEYCYYFOVOERCT-UHFFFAOYSA-N 0.000 description 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
- 238000006676 Baker-Venkataraman rearrangement reaction Methods 0.000 description 1
- 238000003512 Claisen condensation reaction Methods 0.000 description 1
- NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 238000005874 Vilsmeier-Haack formylation reaction Methods 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 150000004777 chromones Chemical class 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940126540 compound 41 Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000012679 convergent method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- CNXMDTWQWLGCPE-UHFFFAOYSA-N ditert-butyl-(2-phenylphenyl)phosphane Chemical group CC(C)(C)P(C(C)(C)C)C1=CC=CC=C1C1=CC=CC=C1 CNXMDTWQWLGCPE-UHFFFAOYSA-N 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
- C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
- C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D335/00—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom
- C07D335/04—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D335/06—Benzothiopyrans; Hydrogenated benzothiopyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
- C07F9/65522—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0072—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the A ring of the steroid being aromatic
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a preparation method of flavonoid and isoflavone compounds, the reaction formula is shown as follows:
Description
Technical Field
The invention relates to the field of organic synthesis, in particular to a preparation method and application of flavone and isoflavone compounds.
Background
Flavones and isoflavones are a very important class of building blocks, widely occurring in natural products and drug molecules with biological activity (Eur J Med Chem,2014,84,206-239). Currently, methods for synthesizing flavonoids and isoflavones fall broadly into two categories (Chem Rev,2014,114,4960-4992;Chin Chem Lett,2020,31,3073-3082; mini-Rev Org Chem,2016,13,31-48; tetrahedron,2012,68, 8523-8538). One is obtained by reactions such as the aromatic reaction Claisen condensation (Med Chem Lett,2012,22,5455-5459), baker-Venkataraman rearrangement (J Chem Soc,1934,10,1767-1969) and Vilsmeier-Haack ([ 8]Org Prep Proced Int,2009,41,69-75), but these strategies mostly only allow the construction of C2 or C3 monosubstituted chromone compounds. The other is obtained by further derivatization of the chromone structure. However, these methods are generally a single task, and the structural diversity of the flavonoids and isoflavonoids obtained is limited, limiting their scope of use.
Therefore, development of a novel efficient and simple synthesis method is particularly important, and flavonoid and isoflavone compounds are synthesized by using simple and easily available raw materials.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention takes the simple and easily obtained iodized chromone compound as the initial raw material, and the flavonoid and isoflavone compound can be obtained by stirring and reacting in an organic solvent at 80-140 ℃ under the action of a palladium catalyst, a norbornene derivative, a phosphine ligand and alkali. The method has the advantages of easily available raw materials, simple operation, good chemical selectivity and wide substrate application range, and provides a very efficient and convergent method for synthesizing important drug molecules and natural products containing chromone structural units.
The invention aims to solve at least one of the technical problems existing in the prior art to a certain extent, and therefore, in a first aspect of the invention, the invention provides a preparation method of flavonoid and isoflavone compounds, wherein the reaction formula is as follows:
wherein the structural formulas of the flavonoid and the isoflavone compound are selected from one of a compound shown in a formula M, a compound shown in a formula J, a compound shown in a formula K and a compound shown in a formula L; b is aryl halide; c is alkene or alkyne; r is R 1 Selected from one of aryl, alkyl, alkoxy and halogen, m is taken from 0,1, 2, X is selected from O or S; r is R 2 Is one of alkyl, ester, nitro, amido, sulfonyl, alkoxy and halogen; n is 1, 2; p is taken from 0,1, 2, 3; r is R 3 And R is 4 Each independently selected from one of aryl, heteroaryl, alkyl, ester, silicon, amide, sulfonyl, phosphino, alkoxy, and hydrogen; r is R 5 Is silicon-based; r is R 6 Is one of alkyl, mercapto, alkoxy, p-toluenesulfonyloxy and halogen; r is taken from 0,1, 2; r is R 7 One selected from hydrogen, heteroaryl, alkyl, ester, hydroxy, cyano, alkoxy and halogen;
preferably, R 2 Is methyl, methoxy, ester, nitro,One of an amide group, a sulfonyl group, and a halogen; r is R 3 And R is 4 Each independently selected from one of naphthyl, heteroaryl, alkyl, ester, silicon, amide, sulfonyl, phosphino, alkoxy, and hydrogen; r is R 6 Is one of alkyl, mercapto, alkoxy, p-toluenesulfonyloxy and halogen; r is R 7 One selected from hydrogen, alkyl, ester, hydroxy, cyano, alkoxy, 2-methoxypyridine, thiophene, dibenzothiophene, and halogen;
the preparation method specifically comprises the following steps: under the inert gas atmosphere, using the compounds shown in the formula A, B and C as starting materials, stirring and reacting in a solvent H under the action of a palladium catalyst D, a phosphine ligand E, norbornene F and alkali G, and separating to obtain the flavonoid and isoflavone compound M, J, K or L.
In one or more embodiments of the invention, B is of the formula
Wherein Y is iodine, bromine or p-toluenesulfonyloxy.
In one or more embodiments of the invention, C is of the formula:
in one or more embodiments of the present invention, a method for preparing flavonoids and isoflavonoids is provided, the reaction formula is as follows:
the preparation method of the flavonoid and isoflavone compound comprises the following steps: under the atmosphere of protective gas, the compound shown in the formula A, the compound B1 (the structural formula is shown as above) and the compound C1 (the structural formula is shown as above) are used as starting materials, and under the action of a palladium catalyst D, a phosphine ligand E, a norbornene derivative F and a base G, the materials are stirred and reacted in a solvent H, and the materials are separated to obtain the flavonoid compound M or J.
In one or more embodiments of the present invention, a method for preparing flavonoids and isoflavonoids is provided, the reaction formula is as follows:
the preparation method of the flavonoid and isoflavone compound comprises the following steps: under the atmosphere of protective gas, taking a compound shown in a formula A, a compound B1 (the structural formula is shown as above) and a compound C2 (the structural formula is shown as above) as starting materials, stirring and reacting in a solvent H under the action of a palladium catalyst D, a phosphine ligand E, a norbornene derivative F and a base G, and separating to obtain the 2, 3-diaryl substituted chromone compound K, namely the flavonoid and isoflavone compound.
In one or more embodiments of the present invention, a method for preparing flavonoids and isoflavonoids is provided, the reaction formula is as follows:
the preparation method of the flavonoid and isoflavone compound comprises the following steps: under the atmosphere of protective gas, taking a compound shown in a formula A, B2 (the structural formula is shown as above) and C2 (the structural formula is shown as above) as starting materials, stirring and reacting in a solvent H under the action of a palladium catalyst D, a phosphine ligand E, a norbornene derivative F and a base G, and separating to obtain the isoflavone compound L.
In one or more embodiments of the present invention, the phosphine ligand E is selected from any one or more of triarylphosphine, dicyclohexyl (2 ',4',6' -triisopropyl- [1,1' -diphenyl ] -2-yl) phosphine, dicyclohexyl (2 ',6' -dimethoxy- [1,1' -diphenyl ] -2-yl) phosphine, 2' - (dicyclohexylphosphino) -N, N-dimethyl- [1,1' -diphenyl ] -2-amine, tris (2-furyl) phosphine, 2- (di-t-butylphosphino) biphenyl.
In one or more embodiments of the present invention, the norbornene derivative F has the structural formula as follows:
wherein R is 8 、R 9 Each independently is an ester group, carbonyl group, cyano group, amide group, or alkyl group; q is an integer, and q is more than or equal to 0 and less than or equal to 8; s is taken from 0,1, 2.
In one or more embodiments of the present invention, the base G is selected from any one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium acetate, cesium acetate, tripotassium phosphate, potassium bicarbonate, and potassium hydroxide.
In one or more embodiments of the present invention, the solvent H is selected from any one or more of 1, 4-epoxyhexa-ne, tetrahydrofuran, ethylene glycol dimethyl ether, toluene, acetonitrile, N-dimethylformamide, and N-methylpyrrolidone.
In one or more embodiments of the invention, the reaction temperature is controlled to be 80-140 ℃.
In one or more embodiments of the invention, the reaction time is controlled to be 18 to 60 hours.
In a second aspect of the invention, the invention provides an application of flavonoids and isoflavones in preparing a umbralisib core skeleton, wherein the flavonoids and isoflavones react with halogen to obtain the umbralisib core skeleton; the chemical formula of the umbralisib core skeleton is shown as the following formula N:
the flavonoid and isoflavone compound is selected from one of a compound shown in the following formula M, a compound shown in the formula J, a compound shown in the formula K and a compound shown in the formula L,
preferably, the flavonoid and isoflavone compound is a compound shown in a formula L;
wherein R is 1 Selected from one of aryl, alkyl, alkoxy and halogen, m is taken from 0,1, 2, X is selected from O or S; r is R 2 Is one of alkyl, ester, nitro, amido, sulfonyl, alkoxy and halogen; n is 1, 2; p is taken from 0,1, 2, 3; r is R 3 And R is 4 Each independently selected from one of aryl, heteroaryl, alkyl, ester, silicon, amide, sulfonyl, phosphino, alkoxy, and hydrogen; r is R 5 Is silicon-based; r is R 6 Is one of alkyl, mercapto, alkoxy, p-toluenesulfonyloxy and halogen; r is taken from 0,1, 2; r is R 7 One selected from hydrogen, heteroaryl, alkyl, ester, hydroxy, cyano, alkoxy and halogen; y is iodine, bromine or p-toluenesulfonyloxy;
preferably, R 2 Is one of methyl, methoxy, ester, nitro, amido, sulfonyl and halogen; r is R 3 And R is 4 Each independently selected from one of naphthyl, heteroaryl, alkyl, ester, silicon, amide, sulfonyl, phosphino, alkoxy, and hydrogen; r is R 6 Is one of alkyl, mercapto, alkoxy, p-toluenesulfonyloxy and halogen; r is R 7 One selected from hydrogen, alkyl, ester, hydroxy, cyano, alkoxy, 2-methoxypyridine, thiophene, dibenzothiophene, and halogen;
preferably, the chemical formula of the flavonoid and isoflavone compound for preparing the umbralisib core skeleton is shown as follows:
compared with the prior art, the invention has the following advantages and beneficial effects:
1. the invention provides a preparation method of flavonoid and isoflavone compounds, which mainly comprises the raw materials of iodo-chromone compounds, aryl or alkyl halides, olefin compounds and aryl potassium trifluoroborate, wherein the raw materials are all commercialized reagents, no special treatment is needed, and the preparation method is low in cost or large in mass production with a simple method.
2. Compared with the catalyst norbornene used in similar reactions in the prior art, the catalyst norbornene derivative used in the reactions related to the preparation method provided by the invention has the advantages that the dosage is greatly reduced, and the preparation cost is reduced.
3. The catalyst used in the reaction related to the preparation method of the invention is relatively cheap metal palladium and phosphorus ligand, which is an important supplement compared with other catalysts or complexes
4. The preparation method has good substrate application range and functional group compatibility;
5. the invention provides a preparation method of flavonoid and isoflavone compounds, which can prepare a large amount of flavonoid compounds, is suitable for industrial production and has great application potential.
6. The invention also provides application of the prepared flavonoid and isoflavone compound in preparing a umbralisib core skeleton.
Detailed Description
The scheme of the present invention will be explained below with reference to examples. It will be appreciated by those skilled in the art that the following examples are illustrative of the present invention and should not be construed as limiting the scope of the invention. The examples are not to be construed as limiting the specific techniques or conditions described in the literature in this field or as per the specifications of the product. The methods used are conventional methods known in the art unless otherwise specified, and the consumables and reagents used are commercially available unless otherwise specified. Unless otherwise defined, the technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In addition, any method or material similar or equivalent to those described may be used in the present invention.
Example 1:
palladium acetate (1.2 mg,0.005 mmol), triphenylphosphine (1.4 mg,0.005 mmol), potassium carbonate (13.8 mg,0.1 mmol) and 3-iodochromone (27.2 mg,0.1 mmol) were added to a reaction tube which was dried and equipped with a magnetic stirrer under argon, followed by dried 1, 4-epoxyhexane (1 mL) in which 1-ethyl formate-2-norbornene (8.3 mg,0.05 mmol) was dissolved. After that, methyl o-bromobenzoate (21.5 mg,0.1 mmol) and styrene (12.5 mg,0.12 mmol) were added again to the above solution. The resulting mixture was reacted at 100℃for 18 hours under an argon atmosphere. After the completion of the reaction, the mixture was cooled to room temperature, filtered through celite, washed with ethyl acetate, the solvent was removed by distillation under reduced pressure, and the compound 1 was isolated and purified by column chromatography (yellow oily liquid, 90% yield).
Examples 2 to 40 are as follows:
example 41:
palladium acetate (1.2 mg,0.005 mmol), triphenylphosphine (1.4 mg,0.005 mmol), potassium carbonate (13.8 mg,0.1 mmol), 3-iodochromone (27.2 mg,0.1 mmol) and potassium phenyltrifluoroborate (27.6 mg,0.15 mmol) were added to a dry reaction tube equipped with a magnetic stirrer under argon and dried tetrahydrofuran (1 mL) in which ethyl 1-formate-2-norbornene (8.3 mg,0.05 mmol) was dissolved. Methyl o-bromobenzoate (21.5 mg,0.1 mmol) was then added to the above solution. The resulting mixture was reacted at 120℃for 36 hours under an argon atmosphere. After the completion of the reaction, the mixture was cooled to room temperature, filtered through celite, washed with ethyl acetate, the solvent was removed by distillation under the reduced pressure, and the compound 41 (colorless oily liquid, 64% yield) was isolated and purified by column chromatography.
Examples 42 to 54 are as follows:
/>
example 55:
palladium acetate (1.2 mg,0.005 mmol), triphenylphosphine (1.4 mg,0.005 mmol), potassium carbonate (13.8 mg,0.1 mmol), 3-iodochromone (27.2 mg,0.1 mmol) and potassium phenyltrifluoroborate (27.6 mg,0.15 mmol) were added to a reaction tube which was dried and equipped with a magnetic stirrer under argon atmosphere, and then dried tetrahydrofuran (1 mL) in which ethyl 1-formate-2-norbornene (8.3 mg,0.05 mmol) and methyl iodide (14.2 mg,0.1 mmol) were dissolved was added. The resulting mixture was reacted at 100℃under an argon atmosphere for 36 hours. After the completion of the reaction, the mixture was cooled to room temperature, filtered through celite, washed with ethyl acetate, the solvent was removed by distillation under the reduced pressure, and the compound 55 (colorless oily liquid, 41% yield) was isolated and purified by column chromatography.
Examples 56-66 are as follows:
/>
example 67:
compound 66 (11.0 mg,0.044 mmol) was added to a dry reaction tube equipped with a magnetic stirrer under argon and 1mL of CCl was added 4 Heating to 80 deg.C, gradually dripping Br 2 (6.8. Mu.L, 0.132 mmol) CCl 4 (0.5 mL) and reacted under dark conditions. The reaction was monitored by GC, after completion of the reaction, cooled to room temperature, quenched with sodium thiosulfate solution, the organics extracted with methylene chloride (3×5 mL), dried over anhydrous sodium sulfate, the solvent removed under reduced pressure and the crude product purified by direct column chromatography to afford compound 67 (colorless oily liquid, 99% yield).
The product obtained in example 1 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.34(dd,J＝7.9,1.7Hz,1H),8.16(dd,J＝7.4,1.8Hz,1H),7.91(d,J＝16.2Hz,1H),7.71–7.62(m,3H),7.57(dd,J＝7.1,1.8Hz,1H),7.45–7.41(m,1H),7.39(d,J＝8.4Hz,1H),7.29–7.22(m,4H),7.19–7.15(m,1H),6.59(d,J＝16.3Hz,1H),3.69(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.53,166.37,163.84,155.57,138.21,134.16,133.90,133.61,132.42,131.35,131.08,130.64,130.58,128.57,127.62,126.54,126.40,125.22,123.88,119.83,118.10,117.81,52.70；HRMS(ESI-TOF):calc’d for C 25 H 19 O 4 + [M+H + ]383.1278,found383.1269.
the product obtained in example 2 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.64–8.62(m,1H),8.09(dd,J＝7.8,1.3Hz,1H),7.66(td,J＝7.5,1.5Hz,1H),7.61–7.54(m,4H),7.48(d,J＝16.3Hz,1H),7.46(dd,J＝7.6,1.3Hz,1H),7.25–7.14(m,5H),6.71(d,J＝16.4Hz,1H),3.71(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ179.75,166.34,150.13,138.18,137.27,136.69,134.29,132.59,131.72,131.34,131.09,131.04,130.56,129.94,129.86,129.63,128.55,127.67,126.70,125.65,122.23,52.58；HRMS(ESI-TOF):calc’d for C 25 H 18 NaO 3 S + [M+Na + ]421.0869,found421.0879.
the product obtained in example 3 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.14(dd,J＝7.4,1.8Hz,1H),7.94(d,J＝16.2Hz,1H),7.69–7.61(m,2H),7.57(d,J＝7.1Hz,1H),7.53(t,J＝8.3Hz,1H),7.26–7.21(m,4H),7.18–7.14(m,1H),6.94(d,J＝8.4Hz,1H),6.84(d,J＝8.3Hz,1H),6.57(d,J＝16.2Hz,1H),4.04(s,3H),3.69(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.40,166.56,161.71,160.31,157.58,138.49,133.86,133.65,133.60,132.30,131.45,131.04,130.85,130.48,128.54,127.45,126.50,119.77,118.95,114.47,109.83,106.40,56.57,52.70；HRMS(ESI-TOF):calc’d for C 26 H 20 NaO 5 + [M+Na + ]435.1203,found435.1201.
the product obtained in example 4 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.15(dd,J＝7.7,1.5Hz,1H),8.12(d,J＝1.0Hz,1H),7.88(d,J＝16.3Hz,1H),7.70–7.62(m,2H),7.56(dd,J＝7.4,1.6Hz,1H),7.46(dd,J＝8.5,2.2Hz,1H),7.30–7.22(m,5H),7.19–7.15(m,1H),6.60(d,J＝16.2Hz,1H),3.68(s,3H),2.49(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.59,166.46,163.68,153.90,138.28,135.14,134.89,134.01,132.37,131.36,131.07,130.72,130.51,128.56,127.57,126.55,125.68,123.55,120.01,117.95,117.58,52.70,21.19；HRMS(ESI-TOF):calc’d for C 26 H 20 NaO 4 + [M+Na + ]419.1254,found419.1244.
the product obtained in example 5 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.18(dd,J＝7.4,1.8Hz,1H),7.97(dd,J＝8.3,2.7Hz,1H),7.90(d,J＝16.2Hz,1H),7.72–7.64(m,2H),7.56(dd,J＝7.1,1.8Hz,1H),7.42–7.35(m,2H),7.28–7.22(m,4H),7.20–7.16(m,1H),6.55(d,J＝16.2Hz,1H),3.71(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.74(d,J＝2.4Hz),165.18(d,J＝209.7Hz),159.73(d,J＝246.0Hz),151.83,138.08,134.44,133.76,132.52,131.31,131.15,130.72,130.54,128.60,127.74,126.58,125.01(d,J＝7.3Hz),121.88(d,J＝25.9Hz),119.97(d,J＝8.0Hz),119.51,117.56,111.16(d,J＝23.9Hz),52.73； 19 F NMR(376MHz,CDCl 3 ):δ-115.40；HRMS(ESI-TOF):calc’d for C 25 H 17 FNaO 4 + [M+Na + ]423.1003,found423.0997.
the product obtained in example 6 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.29(d,J＝2.6Hz,1H),8.19–8.17(m,1H),7.88(d,J＝16.3Hz,1H),7.70–7.66(m,2H),7.60–7.55(m,2H),7.35(d,J＝8.9Hz,1H),7.28–7.22(m,4H),7.20–7.16(m,1H),6.55(d,J＝16.3Hz,1H),3.71(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.31,166.15,164.04,153.88,138.00,134.55,133.80,133.65,132.53,131.28,131.15,131.10,130.74,130.50,128.58,127.76,126.58,125.77,124.79,119.60,119.42,118.19,52.72；HRMS(ESI-TOF):calc’d for C 25 H 17 ClNaO 4 + [M+Na + ]439.0708,found439.0706.
the product obtained in example 7 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.45(d,J＝2.4Hz,1H),8.17(dd,J＝7.6,1.6Hz,1H),7.87(d,J＝16.2Hz,1H),7.72(dd,J＝8.8,2.5Hz,1H),7.66(qd,J＝7.4,1.7Hz,2H),7.56(dd,J＝7.3,1.6Hz,1H),7.29(d,J＝8.9Hz,1H),7.25–7.21(m,4H),7.20–7.16(m,1H),6.54(d,J＝16.3Hz,1H),3.71(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.16,166.15,164.02,154.31,137.99,136.53,134.58,133.64,132.53,131.28,131.16,130.75,130.49,128.99,128.59,127.77,126.59,125.17,119.83,119.41,118.58,118.30,52.73；HRMS(ESI-TOF):calc’d for C 25 H 17 BrNaO 4 + [M+Na + ]483.0202,found483.0198.
the product obtained in example 8 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.15(dd,J＝7.7,1.5Hz,1H),7.92(d,J＝16.3Hz,1H),7.71(d,J＝3.1Hz,1H),7.69–7.62(m,2H),7.56(dd,J＝7.3,1.6Hz,1H),7.34(d,J＝9.1Hz,1H),7.29–7.22(m,5H),7.19–7.15(m,1H),6.59(d,J＝16.2Hz,1H),3.93(s,3H),3.69(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.34,166.42,163.70,157.11,150.51,138.30,134.03,133.98,132.39,131.37,131.09,130.72,130.55,128.60,127.60,126.55,124.46,123.79,120.00,119.29,117.37,105.41,56.07,52.72；HRMS(ESI-TOF):calc’d for C 26 H 20 NaO 5 + [M+Na + ]435.1203,found435.1196.
the product obtained in example 9 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.22(d,J＝8.1Hz,1H),8.16(dd,J＝7.4,1.7Hz,1H),7.91(d,J＝16.3Hz,1H),7.70–7.62(m,2H),7.56(dd,J＝7.2,1.8Hz,1H),7.29–7.22(m,5H),7.19–7.15(m,2H),6.59(d,J＝16.3Hz,1H),3.70(s,3H),2.48(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.44,166.40,163.54,155.69,144.91,138.27,133.99,132.37,131.36,131.04,130.65,130.48,128.54,127.54,126.78,126.51,126.14,121.64,119.97,117.94,117.48,52.68,21.92；HRMS(ESI-TOF):calc’d for C 26 H 20 NaO 4 + [M+Na + ]419.1254,found419.1249.
the product obtained in example 10 is characterized as follows:
1 HNMR(400MHz,CDCl 3 ):δ8.36(dd,J＝8.9,6.3Hz,1H),8.18(dd,J＝7.7,1.4Hz,1H),7.88(dd,J＝16.2,1.0Hz,1H),7.72–7.64(m,2H),7.56(dd,J＝7.4,1.5Hz,1H),7.28–7.22(m,4H),7.20–7.14(m,2H),7.07(dd,J＝8.9,2.4Hz,1H),6.56(dd,J＝16.3,0.9Hz,1H),3.73(s,3H)； 13 CNMR(100MHz,CDCl 3 ):δ176.64,166.15,165.65(d,J＝254.7Hz),163.99,156.45(d,J＝13.2Hz),138.05,134.51,133.63,132.53,131.32,131.14,130.70,130.47,128.99(d,J＝10.5Hz),128.57,127.72,126.55,120.75(d,J＝2.2Hz),119.46,118.20,114.05(d,J＝22.6Hz),104.37(d,J＝25.3Hz),52.71； 19 F NMR(376MHz,CDCl 3 ):δ-103.29；HRMS(ESI-TOF):calc’d for C 25 H 17 FNaO 4 + [M+Na + ]423.1003,found423.1001.
the product obtained in example 11 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.28(d,J＝8.4Hz,1H),8.18(dd,J＝7.6,1.6Hz,1H),7.88(d,J＝16.3Hz,1H),7.72–7.66(m,2H),7.56(dd,J＝7.4,1.6Hz,1H),7.42(d,J＝1.7Hz,1H),7.40(dd,J＝8.4,1.9Hz,1H),7.28–7.22(m,4H),7.20–7.16(m,1H),6.55(d,J＝16.3Hz,1H),3.74(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.74,166.12,163.92,155.62,139.59,138.03,134.57,133.63,132.55,131.32,131.17,130.74,130.45,128.59,127.85,127.76,126.58,126.08,122.41,119.44,118.41,117.86,52.75；HRMS(ESI-TOF):calc’d for C 25 H 17 ClNaO 4 + [M+Na + ]439.0708,found439.0707.
the product obtained in example 12 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.19(d,J＝8.4Hz,1H),8.21–8.14(m,1H),7.88(d,J＝16.2Hz,1H),7.71–7.63(m,2H),7.59(d,J＝1.8Hz,1H),7.56(t,J＝2.0Hz,1H),7.54–7.53(m,1H),7.27–7.22(m,4H),7.20–7.15(m,1H),6.54(d,J＝16.2Hz,1H),3.73(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.85,166.12,163.88,155.58,138.03,134.58,133.64,132.57,131.32,131.18,130.75,130.45,128.85,128.60,127.89,127.81,127.77,126.59,122.77,120.93,119.45,118.45,52.77；HRMS(ESI-TOF):calc’d for C 25 H 17 BrNaO 4 + [M+Na + ]483.0202,found483.0199.
the product obtained in example 13 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.24(d,J＝8.9Hz,1H),8.16(dd,J＝7.6,1.7Hz,1H),7.89(d,J＝16.3Hz,1H),7.71–7.62(m,2H),7.56(dd,J＝7.2,1.7Hz,1H),7.28–7.22(m,4H),7.19–7.15(m,1H),7.01(dd,J＝8.9,2.3Hz,1H),6.79(d,J＝2.3Hz,1H),6.58(d,J＝16.2Hz,1H),3.88(s,3H),3.71(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.99,166.48,164.15,163.32,157.29,138.31,134.10,133.98,132.43,131.41,131.10,130.68,130.51,128.57,127.85,127.57,126.55,119.95,117.94,117.84,114.79,99.81,55.93,52.73；HRMS(ESI-TOF):calc’d for C 26 H 20 NaO 5 + [M+Na + ]435.1203,found435.1195.
the product obtained in example 14 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.18(dd,J＝7.3,1.8Hz,1H),7.88(d,J＝16.3Hz,1H),7.77(ddd,J＝8.2,3.0,1.8Hz,1H),7.69(td,J＝7.3,1.7Hz,2H),7.57(dd,J＝6.9,1.9Hz,1H),7.28–7.24(m,4H),7.24–7.17(m,2H),6.54(d,J＝16.3Hz,1H),3.76(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ175.68,166.04,163.82,158.42(dd,J＝248.6,9.5Hz),151.41(dd,J＝257.4,11.7Hz),141.26(d,J＝10.8Hz),137.88,135.01,133.29,132.57,131.45,131.20,130.93,130.59,128.63,127.91,126.63,126.06(d,J＝8.1Hz),119.13,118.09,108.92(dd,J＝28.8,20.1Hz),106.44(dd,J＝23.4,4.4Hz),53.14(d,J＝84.3Hz)； 19 F NMR(376MHz,CDCl 3 ):δ-112.27,-128.79；HRMS(ESI-TOF):calc’d for C 25 H 16 F 2 NaO 4 + [M+Na + ]441.0909,found441.0906.
the product obtained in example 15 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ10.17(d,J＝8.6Hz,1H),8.16(d,J＝6.9Hz,1H),8.04(d,J＝9.0Hz,1H),7.90(d,J＝8.0Hz,1H),7.82(d,J＝16.4Hz,1H),7.77(d,J＝8.0Hz,1H),7.69–7.60(m,4H),7.42(d,J＝9.0Hz,1H),7.31(d,J＝7.6Hz,2H),7.26(t,J＝7.2Hz,2H),7.19(d,J＝7.1Hz,1H),6.76(d,J＝16.3Hz,1H),3.67(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ179.26,166.53,161.20,156.69,138.20,135.52,134.48,133.61,132.40,131.55,131.08,130.93,130.87,130.84,130.53,129.35,128.58,128.43,127.65,127.27,126.61,120.41,119.99,117.44,116.86,52.69；HRMS(ESI-TOF):calc’d for C 29 H 20 NaO 4 + [M+Na + ]455.1254,found455.1247.
the product obtained in example 16 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(dd,J＝5.5,2.2Hz,1H),8.21(dd,J＝4.3,1.9Hz,1H),7.86(d,J＝16.2Hz,1H),7.70–7.62(m,2H),7.58(ddd,J＝8.6,7.1,1.7Hz,1H),7.53(dd,J＝6.9,1.9Hz,1H),7.38(t,J＝7.5Hz,1H),7.28–7.22(m,5H),7.20–7.14(m,2H),7.10(t,J＝7.3Hz,2H),7.07–7.03(m,2H),6.57(d,J＝16.2Hz,1H),5.11(s,2H)； 13 C NMR(100MHz,CDCl 3 ):δ177.30,165.83,163.64,155.39,138.22,134.68,134.13,133.91,133.43,132.54,131.32,130.57,128.58,128.49,128.46,127.63,126.57,126.39,125.00,123.79,119.81,118.12,117.75,67.77；HRMS(ESI-TOF):calc’d for C 31 H 22 NaO 4 + [M+Na + ]481.1410,found481.1402.
the product obtained in example 17 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.30(dd,J＝8.0,1.6Hz,1H),8.01(d,J＝16.2Hz,1H),7.66–7.63(m,2H),7.60–7.50(m,3H),7.42(t,J＝7.4Hz,1H),7.38–7.34(m,3H),7.27(t,J＝7.5Hz,2H),7.20(t,J＝7.1Hz,1H),6.75(d,J＝16.2Hz,1H),2.94(s,3H),2.90(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.41,169.83,162.13,155.41,138.16,137.42,134.79,133.69,131.54,131.10,130.65,129.02,128.62,127.79,127.70,126.63,126.42,125.31,123.75,119.65,118.50,117.66,39.24,35.10；HRMS(ESI-TOF):calc’d for C 26 H 21 NNaO 3 + [M+Na + ]418.1414,found481.1409.
the product obtained in example 18 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.31(d,J＝7.1Hz,1H),8.01(d,J＝16.3Hz,1H),7.69–7.62(m,3H),7.61–7.54(m,2H),7.44–7.41(m,2H),7.36–7.35(m,2H),7.30–7.26(m,2H),7.22–7.18(m,1H),6.76(d,J＝16.3Hz,1H),3.46(s,3H),3.15(s,3H)； 13 C NMR(150MHz,CDCl 3 ):δ177.58,169.70,162.50,155.39,138.27,135.65,134.66,133.67,131.62,131.31,130.44,129.61,128.63,128.57,127.67,126.65,126.43,125.32,123.75,119.96,118.25,117.73,61.39,32.86；HRMS(ESI-TOF):calc’d for C 26 H 21 NNaO 4 + [M+Na + ]434.1363,found434.1357.
the product obtained in example 19 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.35(dd,J＝8.0,1.7Hz,1H),8.29–8.27(m,1H),7.86(d,J＝16.3Hz,1H),7.82–7.78(m,2H),7.69(ddd,J＝8.6,7.2,1.7Hz,1H),7.65–7.63(m,1H),7.46(t,J＝7.8Hz,1H),7.39(d,J＝8.4Hz,1H),7.25–7.22(m,4H),7.21–7.18(m,1H),6.50(d,J＝16.3Hz,1H),3.16(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.29,160.93,155.37,139.98,137.81,135.22,134.08,133.98,132.61,132.57,131.55,130.68,128.68,127.98,126.70,126.59,125.60,123.99,119.28,117.52,45.07；HRMS(ESI-TOF):calc’d for C 24 H 18 NaO 4 S + [M+Na + ]425.0818,found425.0814.
the product obtained in example 20 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.33(dd,J＝8.0,1.7Hz,1H),8.29(dd,J＝8.0,1.5Hz,1H),7.83–7.73(m,3H),7.67(td,J＝7.1,1.7Hz,2H),7.45(t,J＝7.5Hz,1H),7.37(d,J＝8.4Hz,1H),7.30–7.24(m,4H),7.22–7.18(m,1H),6.61(d,J＝16.2Hz,1H)； 13 C NMR(100MHz,CDCl 3 ):δ177.31,159.87,155.61,148.02,137.78,135.46,133.90,133.83,132.67,131.65,128.64,128.39,127.97,126.65,126.39,125.53,125.42,123.76,118.90,118.87,117.89；HRMS(ESI-TOF):calc’d for C 23 H 15 NNaO 4 + [M+Na + ]392.0893,found392.0887.
the product obtained in example 21 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.32(dd,J＝8.0,1.6Hz,1H),7.87(d,J＝16.1Hz,1H),7.76(d,J＝2.6Hz,1H),7.66(ddd,J＝8.5,7.1,1.7Hz,1H),7.56(d,J＝8.4Hz,1H),7.44(t,J＝7.6Hz,1H),7.35(d,J＝8.5Hz,1H),7.33–7.26(m,5H),7.23–7.19(m,1H),6.63(d,J＝16.1Hz,1H),3.99(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.44,161.64,160.13,155.60,149.13,137.96,135.14,133.80,133.77,128.64,127.89,126.67,126.37,125.42,123.78,120.36,119.50,119.25,118.82,117.87,110.60,56.36；HRMS(ESI-TOF):calc’d for C 24 H 17 NNaO 5 + [M+Na + ]422.0999,found422.0994.
the product obtained in example 22 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.32(dd,J＝8.0,1.7Hz,1H),8.09(d,J＝8.4Hz,1H),7.89(d,J＝16.2Hz,1H),7.64(ddd,J＝8.6,7.1,1.7Hz,1H),7.60(dd,J＝8.5,2.2Hz,1H),7.55(d,J＝2.2Hz,1H),7.42(t,J＝7.6Hz,1H),7.37(d,J＝8.4Hz,1H),7.28–7.22(m,4H),7.20–7.16(m,1H),6.50(d,J＝16.2Hz,1H),3.67(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.32,165.43,161.97,155.54,138.90,138.01,135.54,134.83,133.77,132.51,131.21,130.73,128.98,128.64,127.83,126.63,126.46,125.38,123.85,119.20,118.39,117.82,52.86；HRMS(ESI-TOF):calc’d for C 25 H 17 ClNaO 4 + [M+Na + ]439.0708,found439.0701.
the product obtained in example 23 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.34(dd,J＝8.0,1.7Hz,1H),7.97(d,J＝4.2Hz,1H),7.95(d,J＝10.5Hz,1H),7.64(ddd,J＝8.6,7.0,1.7Hz,1H),7.49–7.47(m,1H),7.46–7.40(m,2H),7.38(d,J＝8.4Hz,1H),7.31–7.23(m,4H),7.20–7.15(m,1H),6.61(d,J＝16.3Hz,1H),3.67(s,3H),2.51(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.56,166.65,164.09,155.56,141.03,138.32,133.99,133.53,132.98,131.64,131.32,131.05,130.59,128.56,127.56,126.57,126.39,125.16,123.89,120.07,118.07,117.79,52.65,21.49；HRMS(ESI-TOF):calc’d for C 26 H 20 NaO 4 + [M+Na + ]419.1254,found419.1250.
the product obtained in example 24 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.33(dd,J＝8.0,1.6Hz,1H),7.96(d,J＝16.3Hz,1H),7.67–7.63(m,2H),7.49(d,J＝8.5Hz,1H),7.43(t,J＝7.6Hz,1H),7.39(d,J＝8.4Hz,1H),7.32–7.30(m,2H),7.28–7.24(m,2H),7.21–7.16(m,2H),6.63(d,J＝16.3Hz,1H),3.95(s,3H),3.68(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.62,166.47,163.89,161.01,155.56,138.35,133.96,133.53,132.94,132.38,128.59,127.57,126.58,126.40,126.03,125.15,123.89,120.17,118.13,117.99,117.77,116.00,55.90,52.80；HRMS(ESI-TOF):calc’d for C 26 H 21 O 5 + [M+Na + ]413.1384,found413.1378.
the product obtained in example 25 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.97(d,J＝2.4Hz,1H),8.51(dd,J＝8.4,2.4Hz,1H),8.34(d,J＝7.2Hz,1H),7.86–7.80(m,2H),7.71–7.67(m,1H),7.47(t,J＝7.6Hz,1H),7.39(d,J＝8.4Hz,1H),7.27–7.26(m,4H),7.24–7.19(m,1H),6.51(d,J＝16.2Hz,1H),3.79(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.11,164.39,160.51,155.57,148.74,139.55,137.58,135.78,134.01,132.95,132.58,128.71,128.14,126.85,126.62,126.52,126.15,125.60,123.77,118.86,118.58,117.77,53.38；HRMS(ESI-TOF):calc’d for C 25 H 17 NNaO 6 + [M+Na + ]450.0948,found450.0946.
the product obtained in example 26 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.32(dd,J＝8.0,1.7Hz,1H),7.89(d,J＝16.3Hz,1H),7.83(dd,J＝8.9,2.7Hz,1H),7.64(ddd,J＝8.6,7.1,1.7Hz,1H),7.55(dd,J＝8.5,5.3Hz,1H),7.42(ddd,J＝8.1,7.1,1.1Hz,1H),7.39–7.34(m,2H),7.28–7.22(m,4H),7.20–7.15(m,1H),6.53(d,J＝16.2Hz,1H),3.69(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.34,165.11(d,J＝2.8Hz),163.23(d,J＝252.9Hz),162.47,155.46,137.96,134.45,133.61,133.42(d,J＝8.4Hz),132.95(d,J＝7.6Hz),129.96(d,J＝3.7Hz),128.53,127.68,126.46,126.35,125.22,123.75,119.60,119.40(d,J＝3.7Hz),118.36(d,J＝3.2Hz),118.14,117.67,52.91； 19 F NMR(376MHz,CDCl 3 ):δ-108.10；HRMS(ESI-TOF):calc’d for C 25 H 17 FNaO 4 + [M+Na + ]423.1003,found423.0995.
the product obtained in example 27 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.31(dd,J＝8.0,1.7Hz,1H),8.19(dd,J＝7.4,1.8Hz,1H),7.73–7.65(m,3H),7.49–7.38(m,4H),7.17(d,J＝15.8Hz,1H),3.72(s,3H),3.69(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.92,168.33,168.11,165.86,155.45,135.94,134.05,133.05,132.71,131.40,131.23,131.11,130.14,126.49,125.73,123.85,122.54,117.87,116.07,52.71,51.61；HRMS(ESI-TOF):calc’d for C 21 H 16 NaO 6 + [M+Na + ]387.0839,found387.0835.
the product obtained in example 28 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.31(dd,J＝8.0,1.6Hz,1H),8.17(dd,J＝7.7,1.5Hz,1H),7.73–7.63(m,3H),7.49(d,J＝8.7Hz,1H),7.45(t,J＝7.5Hz,1H),7.40(d,J＝9.5Hz,1H),7.37(d,J＝2.1Hz,1H),7.07(d,J＝15.7Hz,1H),3.71(s,3H),1.43(s,9H)； 13 C NMR(100MHz,CDCl 3 ):δ177.02,167.85,167.21,165.88,155.44,134.53,133.97,133.11,132.69,131.35,131.23,131.01,130.14,126.49,125.65,124.92,123.91,117.85,116.18,80.14,52.69,28.25；HRMS(ESI-TOF):calc’d for C 24 H 22 NaO 6 + [M+Na + ]429.1309,found429.1305.
the product obtained in example 29 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.31(dd,J＝8.0,1.7Hz,1H),8.17(dd,J＝7.6,1.5Hz,1H),8.14(d,J＝15.1Hz,1H),7.71–7.62(m,3H),7.50(dd,J＝7.3,1.4Hz,1H),7.45(ddd,J＝8.1,7.2,1.1Hz,1H),7.39(dd,J＝8.4,1.1Hz,1H),7.13(d,J＝15.1Hz,1H),3.70(s,3H),3.17(s,3H),2.98(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.57,167.93,167.48,165.92,155.46,133.93,133.32,133.27,132.77,131.39,130.94,130.02,126.31,125.61,123.97,122.05,117.94,116.47,52.63,37.47,35.85；HRMS(ESI-TOF):calc’d for C 22 H 19 NNaO 5 + [M+Na + ]400.1155,found400.1151.
the product obtained in example 30 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.29(dd,J＝8.0,1.7Hz,1H),8.17(dd,J＝7.6,1.6Hz,1H),7.71–7.62(m,3H),7.48–7.33(m,4H),6.93(dd,J＝25.0,17.3Hz,1H),4.00(p,J＝7.2Hz,4H),3.71(s,3H),1.24(t,J＝7.0Hz,6H)； 13 C NMR(100MHz,CDCl 3 ):δ177.16,167.91,165.82,155.46,139.54(d,J＝8.1Hz),134.07,132.98,132.74,131.43,131.20,131.11,130.17,126.38,125.73,124.02,119.67(d,J＝184.4Hz),117.91,116.05(d,J＝21.6Hz),61.77(d,J＝5.3Hz),52.71,16.42(d,J＝6.5Hz)； 31 P NMR(162MHz,CDCl 3 )δ19.35；HRMS(ESI-TOF):calc’d for C 23 H 23 NaO 7 P + [M+Na + ]465.1074,found465.1070.
the product obtained in example 31 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(ddd,J＝9.1,7.6,1.7Hz,2H),8.15(d,J＝15.0Hz,1H),7.84(d,J＝7.2Hz,2H),7.79–7.71(m,2H),7.71–7.65(m,1H),7.57(t,J＝7.3Hz,1H),7.53–7.46(m,3H),7.47–7.43(m,1H),7.40(d,J＝8.4Hz,1H),7.11(d,J＝15.0Hz,1H),3.74(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.63,169.54,165.77,155.46,140.91,134.40,133.27,133.04,132.87,132.37,131.58,131.51,131.22,130.23,129.30,127.76,126.37,126.08,123.66,117.99,114.61,52.83；HRMS(ESI-TOF):calc’d for C 25 H 18 NaO 6 S + [M+Na + ]469.0716,found469.0713.
the product obtained in example 32 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.28(dd,J＝8.0,1.7Hz,1H),8.05–8.03(m,1H),7.70–7.66(m,1H),7.62–7.55(m,2H),7.46–7.39(m,3H),7.27(s,1H),3.75(s,3H),3.71(s,3H),1.59(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.47,167.95,166.69,163.07,156.19,134.05,133.61,133.37,132.20,130.98,130.77,130.73,130.54,130.39,126.43,125.49,123.25,118.42,117.88,52.72,52.07,14.81；HRMS(ESI-TOF):calc’d for C 22 H 18 NaO 6 + [M+Na + ]401.0996,found401.1002.
the product obtained in example 33 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.29(dd,J＝7.9,1.7Hz,1H),8.10(dd,J＝7.7,1.4Hz,1H),7.66–7.59(m,3H),7.51(dd,J＝7.2,1.6Hz,1H),7.43–7.41(m,1H),7.38(d,J＝8.5Hz,1H),6.76(d,J＝19.4Hz,1H),6.44(d,J＝19.3Hz,1H),3.70(s,3H),-0.04(s,9H)； 13 C NMR(100MHz,CDCl 3 ):δ177.61,166.51,163.68,155.72,137.96,134.29,134.02,133.56,132.13,131.20,130.86,130.82,130.33,126.37,125.16,124.13,119.57,117.84,52.70,-1.52；HRMS(ESI-TOF):calc’d for C 22 H 22 NaO 4 Si + [M+Na + ]401.1180,found401.1179.
the product obtained in example 34 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.31(dd,J＝8.0,1.7Hz,1H),8.13(dd,J＝7.8,1.4Hz,1H),7.69–7.60(m,3H),7.51(dd,J＝7.7,1.2Hz,1H),7.42(ddd,J＝8.1,7.2,1.1Hz,1H),7.38(dd,J＝8.4,1.0Hz,1H),6.29–6.16(m,2H),5.32(dd,J＝10.8,3.2Hz,1H),3.71(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.58,166.33,163.84,155.69,133.94,133.61,132.46,131.18,131.06,130.46,130.42,127.81,126.40,125.20,124.01,120.86,118.27,117.83,52.71；HRMS(ESI-TOF):calc’d for C 19 H 14 NaO 4 + [M+Na + ]329.0784,found329.0784.
the product obtained in example 35 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(dd,J＝8.0,1.7Hz,1H),8.06(dd,J＝7.4,1.7Hz,1H),7.64–7.56(m,3H),7.44(dd,J＝7.2,1.7Hz,1H),7.38–7.34(m,2H),7.30(dd,J＝8.4,1.0Hz,1H),3.61(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.43,166.27,163.72,155.53,134.15,133.39,132.39,131.49,131.07,130.16,126.46,125.98,124.96,123.88,118.88,117.68,52.53；HRMS(ESI-TOF):calc’d for C 17 H 12 NaO 4 + [M+Na + ]303.0628,found303.0620.
the product obtained in example 36 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.38(d,J＝7.9Hz,1H),8.19(dd,J＝7.2,1.8Hz,1H),8.07(d,J＝16.3Hz,1H),7.79–7.73(m,2H),7.71–7.65(m,5H),7.61(dd,J＝7.1,1.8Hz,1H),7.47–7.38(m,5H),6.74(d,J＝16.2Hz,1H),3.71(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.55,166.43,163.84,155.60,135.66,134.26,133.94,133.71,133.63,133.09,132.45,131.41,131.12,130.75,130.63,128.18,128.14,127.71,126.95,126.45,126.28,125.93,125.25,123.90,123.32,120.19,118.22,117.83,52.73；HRMS(ESI-TOF):calc’d for C 29 H 20 NaO 4 + [M+Na + ]455.1254,found455.1251.
the product obtained in example 37 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.35(dd,J＝8.0,1.7Hz,1H),8.20(dd,J＝7.4,1.8Hz,1H),7.99–7.93(m,2H),7.74–7.65(m,5H),7.60(dd,J＝7.1,1.7Hz,1H),7.51(s,1H),7.45(t,J＝7.5Hz,1H),7.43–7.36(m,2H),7.27–7.25(m,1H),7.18(d,J＝8.1Hz,2H),7.13(t,J＝7.6Hz,1H),6.65(d,J＝16.4Hz,1H),3.70(s,3H),2.32(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.59,166.27,163.83,155.60,145.11,135.66,135.11,133.97,133.67,132.59,131.30,131.24,130.70,130.55,130.00,129.16,126.95,126.40,125.29,124.93,124.12,123.90,123.50,121.83,121.12,120.47,118.06,117.88,113.87,52.73,21.67；HRMS(ESI-TOF):calc’d for C 34 H 25 NNaO 6 S + [M+Na + ]598.1295,found598.1293.
the product obtained in example 38 is characterized as follows:
1 H NMR(400MHz,Methanol-d 4 ):δ8.22(dd,J＝8.2,1.7Hz,1H),8.12(dd,J＝7.8,1.3Hz,1H),7.78–7.73(m,2H),7.68(td,J＝7.6,1.4Hz,1H),7.59(dd,J＝7.5,1.4Hz,1H),7.51–7.47(m,2H),6.56(d,J＝16.0Hz,1H),6.16(d,J＝16.1Hz,1H),3.71(s,3H),1.14(s,6H)； 13 C NMR(100MHz,CDCl 3 ):δ177.51,166.86,162.98,155.73,144.10,133.82,133.59,132.28,131.04,130.94,130.84,130.42,126.28,125.17,123.74,118.22,117.85,116.84,71.23,52.75,29.66；HRMS(ESI-TOF):calc’d for C 22 H 20 NaO 5 + [M+Na + ]387.1203,found387.1205.
the product obtained in example 39 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.29(dd,J＝8.1,1.7Hz,1H),7.70(d,J＝2.6Hz,1H),7.66(ddd,J＝8.6,7.1,1.7Hz,1H),7.53(d,J＝8.5Hz,1H),7.45–7.39(m,1H),7.36(d,J＝8.4Hz,1H),7.26(q,J＝4.3,3.5Hz,4H),7.05(d,J＝8.5Hz,1H),6.98(d,J＝15.9Hz,1H),6.65(dd,J＝8.4,2.7Hz,1H),6.58(d,J＝2.6Hz,1H),6.19(d,J＝15.9Hz,1H),5.91(s,1H),3.91(s,3H),2.82–2.71(m,2H),2.09(dd,J＝12.9,3.4Hz,1H),1.99–1.81(m,4H),1.71–1.65(m,2H),1.46–1.33(m,5H),1.27–1.20(m,1H),1.13(td,J＝12.6,4.1Hz,1H),0.87(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ178.00,161.58,159.74,155.84,153.86,149.16,142.79,138.27,133.98,133.47,132.50,126.47,126.29,125.51,123.57,120.54,119.71,119.30,117.97,116.87,115.37,112.74,110.29,84.50,56.32,49.57,47.43,43.41,39.44,37.32,32.52,29.76,27.44,26.30,23.50,14.24；HRMS(ESI-TOF):calc’d for C 36 H 35 NNaO 7 + [M+Na + ]616.2306,found616.2293.
the product obtained in example 40 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.28(dd,J＝8.0,1.7Hz,1H),8.09(dd,J＝7.7,1.5Hz,1H),7.74(dd,J＝7.5,1.5Hz,1H),7.65(qd,J＝8.2,7.7,1.7Hz,2H),7.59(td,J＝7.6,1.5Hz,1H),7.45–7.40(m,2H),3.72(s,3H),0.95(s,21H)； 13 C NMR(100MHz,CDCl 3 ):δ176.35,168.92,166.32,155.79,134.01,133.88,132.18,130.85,130.79,130.59,130.11,126.32,125.67,122.97,118.06,109.26,100.24,97.73,52.65,18.65,11.24；HRMS(ESI-TOF):calc’d for C 28 H 32 NaO 4 Si + [M+Na + ]483.1962,found483.1956.
the product obtained in example 41 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.33(dd,J＝8.3,1.7Hz,1H),7.95(dd,J＝7.6,1.5Hz,1H),7.68(ddd,J＝8.8,7.3,1.7Hz,1H),7.46–7.35(m,4H),7.23–7.16(m,6H),3.76(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.27,166.93,162.82,156.27,134.45,133.81,132.48,131.86,131.47,131.02,130.83,130.48,129.87,128.04,127.61,126.60,125.23,123.92,123.26,117.91,52.70；HRMS(ESI-TOF):calc’d for C 23 H 16 NaO 4 + [M+Na + ]379.0941,found379.0934.
the product obtained in example 42 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.10(s,1H),7.94(dd,J＝7.6,1.4Hz,1H),7.49(dd,J＝8.5,2.2Hz,1H),7.41(ddd,J＝14.9,7.4,1.5Hz,2H),7.37–7.31(m,2H),7.21–7.16(m,5H),3.75(s,3H),2.49(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.32,167.01,162.65,154.57,135.16,135.08,134.54,132.66,131.80,131.46,131.07,130.89,130.45,129.80,128.03,127.54,125.85,123.57,123.08,117.67,52.70,21.14；HRMS(ESI-TOF):calc’d for C 24 H 18 NaO 4 + [M+Na + ]393.1097,found393.1109.
the product obtained in example 43 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ7.97–7.94(m,2H),7.46–7.33(m,4H),7.26–7.16(m,6H),3.77(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.57(d,J＝2.4Hz),166.77,163.17,159.74(d,J＝246.6Hz),152.52,134.28,132.17,131.95,131.42,130.95,130.70,130.53,130.01,128.10,127.74,125.07(d,J＝7.3Hz),122.67,122.06(d,J＝25.5Hz),120.04(d,J＝8.2Hz),111.36(d,J＝23.6Hz),52.72； 19 F NMR(376MHz,CDCl 3 ):δ-115.47；HRMS(ESI-TOF):calc’d for C 23 H 15 FNaO 4 + [M+Na + ]397.0847,found397.0849.
the product obtained in example 44 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.28(dd,J＝8.0,1.7Hz,1H),7.66(ddd,J＝8.7,7.2,1.7Hz,1H),7.41(td,J＝7.5,1.1Hz,1H),7.39–7.26(m,6H),7.25–7.18(m,4H),3.01(s,3H),2.80(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.04,170.12,161.46,156.15,136.88,133.74,132.44,131.70,131.41,129.50,128.74,128.08,127.66,127.03,126.74,125.25,123.96,123.68,117.65,39.15,35.10；HRMS(ESI-TOF):calc’d for C 24 H 19 NNaO 3 + [M+Na + ]392.1257,found392.1260.
the product obtained in example 45 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.32(dd,J＝8.0,1.7Hz,1H),8.08(dd,J＝7.9,1.5Hz,1H),7.70(ddd,J＝8.6,7.2,1.7Hz,1H),7.56–7.47(m,2H),7.47–7.43(m,1H),7.40(d,J＝8.4Hz,1H),7.28(d,J＝1.7Hz,1H),7.23(s,5H)； 13 C NMR(100MHz,CDCl 3 ):δ177.06,159.40,156.28,148.22,134.11,133.28,132.68,131.83,130.95,130.85,129.00,128.36,128.09,126.59,125.58,124.91,123.90,118.05；HRMS(ESI-TOF):calc’d for C 21 H 13 NNaO 4 + [M+Na + ]366.0737,found366.0728.
the product obtained in example 46 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.32(dd,J＝7.9,1.7Hz,1H),7.97(dd,J＝7.6,1.5Hz,1H),7.69(ddd,J＝8.6,7.2,1.7Hz,1H),7.50–7.37(m,4H),7.22–7.11(m,2H),6.98–6.94(m,2H),6.92–6.84(m,1H),3.77(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.93,166.78,163.23,162.50(d,J＝245.5Hz),156.26,134.74(d,J＝8.7Hz),134.15,134.00,132.04,131.31,130.75,130.62,130.15,129.50(d,J＝8.6Hz),126.84(d,J＝3.1Hz),126.59,125.41,123.82,122.24,118.16,117.96,114.66(d,J＝21.1Hz),52.76； 19 F NMR(376MHz,CDCl 3 ):δ-113.72；HRMS(ESI-TOF):calc’d for C 23 H 15 FNaO 4 + [M+Na + ]397.0847,found397.0845.
the product obtained in example 47 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.32(dd,J＝8.2,1.6Hz,1H),7.95(dd,J＝7.3,1.7Hz,1H),7.69(td,J＝7.7,1.7Hz,1H),7.48–7.38(m,4H),7.21(dd,J＝7.2,1.7Hz,1H),7.15–7.06(m,3H),7.00(dt,J＝7.0,1.7Hz,1H),3.77(s,3H),2.30(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.07,166.86,163.00,156.25,138.01,134.38,133.89,133.20,132.00,131.38,130.79,130.49,129.99,129.21,128.37,127.97,126.59,126.33,125.31,123.88,122.85,117.94,52.74,16.03；HRMS(ESI-TOF):calc’d for C 24 H 18 NaO 4 S + [M+Na + ]425.0818,found425.0818.
the product obtained in example 48 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.33–8.30(m,1H),7.95(dd,J＝7.4,1.6Hz,1H),7.69–7.65(m,1H),7.45–7.36(m,4H),7.18(dd,J＝7.5,1.6Hz,1H),7.13(d,J＝8.7Hz,2H),6.75(d,J＝8.7Hz,2H),3.75(s,3H),3.75(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.55,167.03,162.55,158.97,156.26,134.67,133.73,132.19,131.91,131.50,130.84,130.48,129.76,126.60,125.15,124.62,123.87,122.81,117.88,113.63,55.27,52.69；HRMS(ESI-TOF):calc’d for C 24 H 18 NaO 5 + [M+Na + ]409.1046,found409.1042.
the product obtained in example 49 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.30(dd,J＝7.9,1.7Hz,1H),7.96(dd,J＝7.8,1.4Hz,1H),7.69(ddd,J＝8.7,7.2,1.7Hz,1H),7.62–7.59(m,2H),7.49–7.38(m,4H),7.25(d,J＝8.2Hz,2H),7.12(d,J＝8.7Hz,3H),6.81(d,J＝8.6Hz,2H),3.75(s,3H),2.43(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.92,166.67,163.14,156.23,148.95,145.35,134.18,134.02,132.34,132.28,131.92,131.59,131.36,130.83,130.52,130.01,129.79,128.64,126.49,125.43,123.74,122.06,122.00,117.96,52.74,21.84；HRMS(ESI-TOF):calc’d for C 30 H 22 NaO 7 S + [M+Na + ]549.0978,found549.0985.
the product obtained in example 50 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.33–8.31(m,1H),7.95(dd,J＝7.6,1.6Hz,1H),7.67(ddd,J＝8.8,7.5,1.8Hz,1H),7.47–7.35(m,4H),7.19(dd,J＝7.5,1.5Hz,1H),7.09(d,J＝8.1Hz,2H),7.01(d,J＝7.8Hz,2H),3.75(s,3H),2.26(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.42,166.99,162.55,156.25,137.25,134.59,133.72,131.87,131.48,130.81,130.45,129.77,129.35,128.83,126.60,125.14,123.89,123.18,117.87,52.68,21.39；HRMS(ESI-TOF):calc’d for C 24 H 18 NaO 4 + [M+Na + ]393.1097,found393.1096.
the product obtained in example 51 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.32(dd,J＝8.4,1.7Hz,1H),7.95–7.93(m,1H),7.66(ddd,J＝8.8,7.2,1.7Hz,1H),7.44–7.37(m,4H),7.21(dd,J＝6.8,2.2Hz,1H),7.01(d,J＝2.2Hz,1H),6.94(dd,J＝8.4,2.3Hz,1H),6.64(d,J＝8.4Hz,1H),3.75(s,6H),2.10(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.67,167.07,162.39,157.22,156.25,134.74,133.67,133.18,131.85,131.45,130.83,130.39,129.67,129.51,126.61,126.14,125.09,124.09,123.89,123.06,117.88,109.64,55.32,52.67,16.34；HRMS(ESI-TOF):calc’d for C 25 H 20 NaO 5 + [M+Na + ]423.1203,found423.1204.
the product obtained in example 52 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.31(dd,J＝8.0,1.7Hz,1H),8.00(dd,J＝7.5,1.7Hz,1H),7.92(d,J＝2.4Hz,1H),7.69(ddd,J＝8.7,7.2,1.7Hz,1H),7.53(dd,J＝8.5,2.4Hz,1H),7.49–7.41(m,4H),7.20(dd,J＝7.0,1.9Hz,1H),6.65(d,J＝8.5Hz,1H),3.85(s,3H),3.76(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.32,166.67,163.33,163.27,156.30,148.63,141.20,134.26,134.00,132.26,131.40,130.83,130.75,130.16,126.53,125.39,123.64,121.59,119.88,117.98,110.28,53.54,52.73；HRMS(ESI-TOF):calc’d for C 23 H 17 NNaO 5 + [M+Na + ]410.0999,found410.1001.
the product obtained in example 53 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.34(dd,J＝7.9,1.7Hz,1H),8.06–8.04(m,1H),7.68(ddd,J＝8.6,7.2,1.7Hz,1H),7.53–7.47(m,2H),7.48–7.39(m,2H),7.38–7.34(m,1H),7.28–7.26(m,1H),6.83(dd,J＝5.1,3.6Hz,1H),6.76(dd,J＝3.6,1.2Hz,1H),3.75(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.59,166.51,163.22,155.97,134.70,133.95,132.53,132.40,130.85,130.75,130.65,130.27,129.29,127.11,126.66,126.24,125.42,123.40,117.92,117.15,52.72；HRMS(ESI-TOF):calc’d for C 21 H 14 NaO 4 S + [M+Na + ]385.0505,found385.0497.
the product obtained in example 54 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.36(dd,J＝8.2,1.7Hz,1H),8.10(d,J＝1.7Hz,1H),8.03–7.97(m,1H),7.94(dd,J＝7.7,1.4Hz,1H),7.82–7.78(m,1H),7.71(ddd,J＝8.8,7.2,1.7Hz,1H),7.66(d,J＝8.3Hz,1H),7.49–7.44(m,2H),7.43–7.40(m,2H),7.37(dd,J＝7.6,1.5Hz,1H),7.32(td,J＝7.5,1.4Hz,1H),7.26–7.21(m,2H),3.80(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.42,166.99,163.10,156.31,139.70,138.88,135.59,135.51,134.41,133.91,132.01,131.49,130.85,130.48,129.96,129.56,128.80,126.77,126.62,125.33,124.43,124.30,123.90,123.02,122.87,122.46,121.73,117.96,52.76；HRMS(ESI-TOF):calc’d for C 29 H 18 NaO 4 S + [M+Na + ]485.0818,found485.0828.
the product obtained in example 55 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.24(dd,J＝7.9,1.7Hz,1H),7.66(ddd,J＝8.6,7.1,1.7Hz,1H),7.48–7.41(m,3H),7.41–7.34(m,2H),7.32–7.27(m,2H),2.33(s,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.93,163.45,156.06,133.48,133.27,130.57,128.55,127.92,126.45,124.96,123.81,123.66,117.78,19.70；HRMS(ESI-TOF):calc’d for C 16 H 12 NaO 2 + [M+Na + ]259.0730,found259.0727.
the product obtained in example 56 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.24(dd,J＝7.9,1.7Hz,1H),7.67(ddd,J＝8.7,7.1,1.7Hz,1H),7.48–7.35(m,5H),7.29–7.26(m,2H),2.60(q,J＝7.5Hz,2H),1.27(t,J＝7.6Hz,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.25,167.54,156.18,133.45,133.24,130.49,128.58,127.91,126.43,124.92,123.64,123.21,117.82,26.31,12.10；HRMS(ESI-TOF):calc’d for C 17 H 14 NaO 2 + [M+Na + ]273.0886,found273.0884.
the product obtained in example 57 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ7.86(dd,J＝8.3,3.1Hz,1H),7.50–7.41(m,3H),7.41–7.34(m,2H),7.28–7.25(m,2H),2.60(q,J＝7.5Hz,2H),1.26(t,J＝7.5Hz,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.47(d,J＝2.2Hz),167.86,159.51(d,J＝245.7Hz),152.37,132.87,130.40,128.62,128.03,124.72(d,J＝7.3Hz),122.60,121.65(d,J＝25.5Hz),119.89(d,J＝8.4Hz),111.11(d,J＝23.4Hz),26.27,12.03； 19 F NMR(376MHz,CDCl 3 ):δ-115.94；HRMS(ESI-TOF):calc’d for C 17 H 13 FNaO 2 + [M+Na + ]291.0792,found291.0795.
the product obtained in example 58 was characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(dd,J＝8.0,1.7Hz,1H),7.66(ddd,J＝8.7,7.1,1.7Hz,1H),7.47–7.35(m,5H),7.28–7.26(m,2H),2.57(t,J＝7.7Hz,2H),1.69(dq,J＝9.1,7.6Hz,2H),1.36–1.25(m,2H),0.85(t,J＝7.3Hz,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.23,166.79,156.15,133.44,133.29,130.57,128.54,127.88,126.43,124.91,123.71,123.63,117.81,32.42,29.71,22.43,13.84；HRMS(ESI-TOF):calc’d for C 19 H 18 NaO 2 + [M+Na + ]301.1199,found301.1200.
the product obtained in example 59 was characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(dd,J＝8.0,1.7Hz,1H),7.67(ddd,J＝8.8,7.0,1.7Hz,1H),7.47–7.35(m,5H),7.28–7.26(m,2H),3.35(t,J＝6.2Hz,2H),3.26(s,3H),2.69–2.65(m,2H),2.01–1.94(m,2H)； 13 C NMR(100MHz,CDCl 3 ):δ177.19,166.10,156.13,133.52,133.11,130.54,128.60,127.97,126.45,124.99,123.91,123.63,117.82,71.65,58.65,29.63,27.53；HRMS(ESI-TOF):calc’d for C 19 H 18 NaO 3 + [M+Na + ]317.1148,found 317.1145.
the product obtained in example 60 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(dd,J＝7.9,1.7Hz,1H),7.67(ddd,J＝8.7,7.1,1.8Hz,1H),7.47–7.35(m,5H),7.29–7.26(m,2H),3.62(t,J＝6.3Hz,2H),2.71–2.69(t,J＝7.6Hz,2H),1.99–1.92(m,2H),1.59(s,1H)； 13 C NMR(100MHz,CDCl 3 ):δ177.15,165.99,156.12,133.58,133.08,130.49,128.69,128.06,126.46,125.05,123.95,123.60,117.80,61.90,30.41,29.21；HRMS(ESI-TOF):calc’d for C 18 H 16 NaO 3 + [M+Na + ]303.0992,found 303.0987.
the product obtained in example 61 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.24(dd,J＝8.0,1.7Hz,1H),7.69(ddd,J＝8.7,7.1,1.8Hz,1H),7.48–7.38(m,5H),7.27–7.24(m,2H),2.77–2.74(m,2H),2.36(t,J＝7.2Hz,2H),2.07(p,J＝7.3Hz,2H)； 13 C NMR(100MHz,CDCl 3 ):δ176.97,163.62,156.00,133.83,132.51,130.36,128.87,128.35,126.55,125.32,124.57,123.58,118.78,117.81,31.48,23.45,16.97；HRMS(ESI-TOF):calc’d for C 19 H 15 NNaO 2 + [M+Na + ]312.0995,found 312.0992.
the product obtained in example 62 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(dd,J＝7.9,1.7Hz,1H),7.67(ddd,J＝8.7,7.1,1.7Hz,1H),7.47–7.35(m,5H),7.27–7.25(m,2H),4.05(q,J＝7.1Hz,2H),2.64(t,J＝7.6Hz,2H),2.31(t,J＝7.4Hz,2H),2.04(p,J＝7.5Hz,2H),1.20(t,J＝7.1Hz,3H)； 13 C NMR(100MHz,CDCl 3 ):δ177.14,172.83,165.34,156.09,133.59,132.96,130.50,128.65,128.03,126.45,125.06,124.13,123.59,117.86,60.63,33.57,31.91,22.73,14.30；HRMS(ESI-TOF):calc’d for C 21 H 20 NaO 4 + [M+Na + ]359.1254,found359.1246.
the product obtained in example 63 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.24(dd,J＝7.9,1.7Hz,1H),7.67(ddd,J＝8.6,7.1,1.7Hz,1H),7.48–7.36(m,5H),7.27–7.25(m,2H),3.46(t,J＝6.4Hz,2H),2.62(t,J＝7.5Hz,2H),1.92–1.82(m,2H),1.83–1.73(m,2H)； 13 C NMR(100MHz,CDCl 3 ):δ177.14,165.66,156.11,133.60,133.03,130.51,128.68,128.06,126.47,125.07,124.02,123.62,117.83,44.41,31.89,31.80,24.74；HRMS(ESI-TOF):calc’d for C 19 H 17 ClNaO 2 + [M+Na + ]335.0809,found335.0803.
the product obtained in example 64 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(dd,J＝8.0,1.7Hz,1H),7.66(ddd,J＝8.7,7.1,1.7Hz,1H),7.47–7.35(m,5H),7.28–7.26(m,2H),4.87(t,J＝4.3Hz,1H),4.01–3.77(m,4H),2.75–2.71(m,2H),2.11–2.04(m,2H)； 13 C NMR(100MHz,CDCl 3 ):δ177.18,165.65,156.11,133.53,132.98,130.51,128.59,128.00,126.45,125.00,123.81,123.64,117.82,103.32,65.14,31.23,27.13；HRMS(ESI-TOF):calc’d for C 20 H 18 NaO 4 + [M+Na + ]345.1097,found 345.1092.
the product obtained in example 65 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ8.23(dd,J＝8.0,1.7Hz,1H),7.68(ddd,J＝8.6,7.1,1.8Hz,1H),7.48(d,J＝8.4Hz,1H),7.42–7.35(m,4H),7.10–7.07(m,2H),6.83(s,1H),6.76(dd,J＝8.1,1.9Hz,1H),6.63(d,J＝8.1Hz,1H),4.52(t,J＝8.6Hz,2H),3.10(t,J＝8.7Hz,2H),2.98–2.90(m,2H),2.87–2.77(m,2H)； 13 C NMR(100MHz,CDCl 3 ):δ177.19,165.45,158.82,156.10,133.54,132.99,132.08,130.51,128.47,127.97,127.91,127.33,126.47,125.00,124.97,124.26,123.63,117.78,109.24,71.32,35.13,33.06,29.84；HRMS(ESI-TOF):calc’d for C 25 H 20 NaO 3 + [M+Na + ]391.1305,found 391.1301.
the product obtained in example 66 is characterized as follows:
1 H NMR(400MHz,CDCl 3 ):δ7.85(dd,J＝8.2,3.1Hz,1H),7.48(dd,J＝9.2,4.2Hz,1H),7.44–7.36(m,2H),7.09(td,J＝8.6,2.6Hz,1H),7.04(d,J＝7.6Hz,1H),6.99(dt,J＝9.5,2.1Hz,1H),2.60(q,J＝7.6Hz,2H),1.27(t,J＝7.5Hz,3H)； 13 C NMR(100MHz,CDCl 3 ):δ176.19,168.04,162.89(d,J＝246.4Hz),159.61(d,J＝246.3Hz),152.38,135.01(d,J＝8.4Hz),130.17(d,J＝8.6Hz),126.24(d,J＝2.9Hz),124.65(d,J＝7.3Hz),121.88(d,J＝25.5Hz),121.64,119.96(d,J＝8.0Hz),117.61(d,J＝21.4Hz),115.12(d,J＝21.0Hz),111.16(d,J＝23.9Hz),26.29,11.99； 19 F NMR(376MHz,CDCl 3 ):δ-113.01,-115.59；HRMS(ESI-TOF):calc’d for C 17 H 12 F 2 NaO 2 + [M+Na + ]309.0698,found309.0699.
the product obtained in example 67 was characterized as follows:
1 H NMR(400MHz,DMSO-d6):δ7.91(dd,J＝9.2,4.2Hz,1H),7.80(td,J＝8.6,3.1Hz,1H),7.74(dd,J＝8.3,3.1Hz,1H),7.55(q,J＝7.9Hz,1H),7.31(td,J＝8.9,2.6Hz,1H),7.24–7.14(m,2H),4.98(q,J＝6.8Hz,1H),1.97(d,J＝6.8Hz,3H)； 13 C NMR(100MHz,DMSO-d6):δ175.29,162.16,161.95(d,J＝244.1Hz),159.17(d,J＝244.8Hz),151.65,133.55(d,J＝8.2Hz),130.53(d,J＝8.6Hz),126.12,123.80(d,J＝7.4Hz),123.04(d,J＝25.4Hz),121.21(d,J＝8.5Hz),119.74,117.16,115.37(d,J＝20.9Hz),109.96(d,J＝23.7Hz),42.76,22.07； 19 F NMR(376MHz,DMSO-d6):δ-113.04,-114.86；HRMS(ESI-TOF):calc’d for C 17 H 12 BrF 2 O 2 + [M+H + ]364.9983,found364.9978.
while embodiments of the present invention have been shown and described above, it should be understood that the above embodiments are illustrative and not to be construed as limiting the present invention, and that variations, modifications, alternatives and variations of the above embodiments may be made by those skilled in the art within the scope of the present invention and are intended to be included within the scope of the present invention.
Claims (4)
1. A preparation method of flavonoid and isoflavone compounds is characterized in that the reaction formula is as follows:
the structural formulas of the flavonoid and isoflavone compounds are selected from one of a compound shown in a formula M, a compound shown in a formula J, a compound shown in a formula K and a compound shown in a formula L; b is aryl halide; c is alkene or alkyne; r is R 1 Selected from one of aryl, alkyl, alkoxy and halogen, m is taken from 0,1, 2, X is selected from O or S; r is R 2 Is one of alkyl, ester, nitro, amido, sulfonyl, alkoxy and halogen; n is 1, 2; p is taken from 0,1, 2, 3; r is R 3 And R is 4 Each independently selected from one of aryl, heteroaryl, alkyl, ester, silicon, amide, sulfonyl, phosphino, alkoxy, and hydrogen; r is R 5 Is silicon-based; r is R 6 Is one of alkyl, mercapto, alkoxy, p-toluenesulfonyloxy and halogen; r is taken from 0,1, 2; r is R 7 One selected from hydrogen, heteroaryl, alkyl, ester, hydroxy, cyano, alkoxy and halogen;
the preparation method specifically comprises the following steps: under the inert gas atmosphere, taking a compound shown in a formula A, B and C as starting materials, stirring and reacting in a solvent H under the action of a palladium catalyst D, a phosphine ligand E, a norbornene derivative F and alkali G, and separating to obtain the flavonoid and isoflavone compound;
the structural formula B is
Wherein Y is iodine, bromine or p-toluenesulfonyloxy;
the structural formula C is as follows:
the phosphine ligand E is selected from any one or more of triarylphosphine, dicyclohexyl (2 ',4',6' -triisopropyl- [1,1' -diphenyl ] -2-yl) phosphine, dicyclohexyl (2 ',6' -dimethoxy- [1,1' -diphenyl ] -2-yl) phosphine, 2' - (dicyclohexylphosphino) -N, N-dimethyl- [1,1' -diphenyl ] -2-amine, tri (2-furyl) phosphine and 2- (di-tert-butyl phosphine) biphenyl;
the alkali G is selected from any one or more of sodium carbonate, potassium carbonate, cesium carbonate, potassium acetate, cesium acetate, tripotassium phosphate, potassium bicarbonate and potassium hydroxide;
the solvent H is selected from any one or more of 1, 4-epoxyhexaane, tetrahydrofuran, ethylene glycol dimethyl ether, toluene, acetonitrile, N-dimethylformamide and N-methylpyrrolidone;
the palladium catalyst D is palladium acetate;
the structural formula of the norbornene derivative F is shown as follows:
wherein R is 8 、R 9 Each independently is an ester group, carbonyl group, cyano group, amide group, or alkyl group; q is an integer, and q is more than or equal to 0 and less than or equal to 8; s is taken from 0,1, 2.
2. The method for preparing flavonoid and isoflavone compound according to claim 1, wherein the reaction temperature is controlled to be 80-140 ℃.
3. The method for preparing flavonoid and isoflavone compound according to claim 1, wherein the reaction time is controlled to be 18-60 hours.
4. An application of isoflavone compound prepared by the preparation method of flavonoid and isoflavone compound in preparing a umbralisib core skeleton, characterized in that the isoflavone compound reacts with halogen to obtain the umbralisib core skeleton; the chemical formula of the umbralisib core skeleton is shown as the following formula N:
the isoflavone compound is a compound shown in a formula L,
wherein R is 1 One selected from aryl, alkyl, alkoxy and halogen, m is taken from 0,1, 2, X is O; p is taken from 0,1, 2, 3; r is R 6 Is one of alkyl, mercapto, alkoxy, p-toluenesulfonyloxy and halogen; r is taken from 0,1, 2; r is R 7 One selected from the group consisting of a hydrogen atom, a heterocyclic aryl group, an alkyl group, an ester group, a hydroxyl group, a cyano group, an alkoxy group, and a halogen; y is iodine or bromine;
the chemical formula of the isoflavone compound for preparing the umbralisib core skeleton is shown as follows:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111095970.0A CN113773294B (en) | 2021-09-18 | 2021-09-18 | Preparation method and application of flavone and isoflavone compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111095970.0A CN113773294B (en) | 2021-09-18 | 2021-09-18 | Preparation method and application of flavone and isoflavone compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN113773294A CN113773294A (en) | 2021-12-10 |
| CN113773294B true CN113773294B (en) | 2023-07-21 |
Family
ID=78852119
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111095970.0A Active CN113773294B (en) | 2021-09-18 | 2021-09-18 | Preparation method and application of flavone and isoflavone compounds |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113773294B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945389A (en) * | 2014-03-27 | 2015-09-30 | 中国科学院上海药物研究所 | Xanthone cross-color ketone compound as well as preparation method and application thereof |
| WO2016054491A1 (en) * | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2535338A1 (en) * | 1975-08-07 | 1977-02-17 | Bayer Ag | Substd. chroman (4) ones prodn. - by reacting (2)-hydroxy-acetophenones and ketootkk ketones in presence of sec. amines |
| US8158810B2 (en) * | 2006-07-27 | 2012-04-17 | Gilead Sciences, Inc. | ALDH-2 inhibitors in the treatment of addiction |
| CN102241657A (en) * | 2011-05-04 | 2011-11-16 | 陕西师范大学 | Synthesis of isoflavone compound through Stille crossed coupling reaction |
| CN111732567B (en) * | 2020-06-17 | 2022-07-08 | 遵义医科大学 | Chromone framework-containing polycyclic compound, and preparation method and application thereof |
| CN112898256B (en) * | 2021-01-29 | 2023-01-31 | 遵义医科大学 | Preparation method of 1, 2-dihydrocyclopenta [ b ] chromene-3, 9-diketone compound |
-
2021
- 2021-09-18 CN CN202111095970.0A patent/CN113773294B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945389A (en) * | 2014-03-27 | 2015-09-30 | 中国科学院上海药物研究所 | Xanthone cross-color ketone compound as well as preparation method and application thereof |
| WO2016054491A1 (en) * | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN113773294A (en) | 2021-12-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108341828A (en) | It is used to prepare the method and its intermediate of eribulin | |
| CN105175346B (en) | A kind of method of synthesizing rosuvastatin spit of fland calcium intermediate | |
| Meshram et al. | Bismuthtriflate-catalyzed Reaction of N-Alkylisatins with Allyltrimethylsilane | |
| CN113773294B (en) | Preparation method and application of flavone and isoflavone compounds | |
| CN115894554A (en) | Preparation method of phosphonic acid compound | |
| JP2019014675A (en) | Phenyl phenol derivative and method for producing dibenzofuran derivative using the same | |
| CN110240572B (en) | Synthesis method of trans-1, 1-cyclopropane dicarboxylic acid ester | |
| CA2708143C (en) | Intermediates in the synthesis of zearalenone macrolide analogs | |
| CN106243079B (en) | The Preparation Method And Their Intermediate compound of bicyclic alcohols | |
| CN108727323B (en) | Method for catalytically synthesizing trifluoromethyl substituted homoisoflavone compound by using N-heterocyclic carbene | |
| CN106317001B (en) | The method that one pot reaction prepares polycyclic furan compound under no catalyst, condition of no solvent | |
| CN104926674A (en) | (Z)-3-dimethylamino-2-phenoxy-alpha, beta-unsaturated amide and preparation method thereof | |
| CN112174819A (en) | Alkenyl aryl ether and preparation method thereof | |
| CN106243072B (en) | The method that alkali-free, condition of no solvent prepare furane derivative by Feist-Benary reactions | |
| JP5448572B2 (en) | Acetyl compound, method for producing the acetyl compound, and method for producing a naphthol compound using the acetyl compound | |
| EP3233776B1 (en) | Formation of chromanes based on intermolecular reaction of alkynes with dimethylfuran in the presence of gold(i) complexes | |
| CN105111175B (en) | Synthetic method of 3-hydroxy-6-nitroflavone prepared through adopting one-step method | |
| CN115433097B (en) | Method for preparing 4-butoxybenzoic acid (2-diethylaminoethyl) ester without metal | |
| JP2005314260A (en) | Method for producing flavone c glycoside | |
| CA2902009A1 (en) | Isohexide monotriflates and process for synthesis thereof | |
| CN114835694B (en) | Method for synthesizing chiral 3, 4-dihydro-2H-pyran compounds in aqueous medium | |
| KR102381035B1 (en) | Novel Synthtic Method for gaylussacin derivatives | |
| CN110577483B (en) | Green synthesis method of 3, 3-disubstituted-2-indolone | |
| CN110467556B (en) | Nucleophilic reaction method for catalyzing imine ions and acetophenone by nickel | |
| JP5280858B2 (en) | 1,1'-Biphenyls Axial Chirality Ligand Linked at 5,5 'Position and Method for Producing the Same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |