CN115572287A - Chiral amino acid C-glucoside and synthesis method thereof - Google Patents
Chiral amino acid C-glucoside and synthesis method thereof Download PDFInfo
- Publication number
- CN115572287A CN115572287A CN202211216395.XA CN202211216395A CN115572287A CN 115572287 A CN115572287 A CN 115572287A CN 202211216395 A CN202211216395 A CN 202211216395A CN 115572287 A CN115572287 A CN 115572287A
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- Prior art keywords
- nmr
- phenyl
- amino acid
- acetone
- chiral amino
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- 150000001413 amino acids Chemical class 0.000 title abstract description 12
- 238000001308 synthesis method Methods 0.000 title abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims abstract description 7
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 6
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims abstract description 4
- JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 claims abstract description 4
- HFMDLUQUEXNBOP-UHFFFAOYSA-N n-[4-amino-1-[[1-[[4-amino-1-oxo-1-[[6,9,18-tris(2-aminoethyl)-15-benzyl-3-(1-hydroxyethyl)-12-(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1-oxobutan-2-yl] Chemical compound OS(O)(=O)=O.N1C(=O)C(CCN)NC(=O)C(NC(=O)C(CCN)NC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)CCCCC(C)CC)CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C1CC1=CC=CC=C1 HFMDLUQUEXNBOP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000005037 alkyl phenyl group Chemical group 0.000 claims abstract description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 31
- -1 amino acid C-glycoside Chemical class 0.000 claims description 31
- 229930182476 C-glycoside Natural products 0.000 claims description 15
- 239000003054 catalyst Substances 0.000 claims description 12
- 239000003446 ligand Substances 0.000 claims description 12
- 150000001875 compounds Chemical class 0.000 claims description 11
- 229910052763 palladium Inorganic materials 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 229940125904 compound 1 Drugs 0.000 claims description 8
- 229940125782 compound 2 Drugs 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 125000004799 bromophenyl group Chemical group 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 3
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 6
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 239000000348 glycosyl donor Substances 0.000 abstract description 3
- 239000002243 precursor Substances 0.000 abstract description 3
- 125000001424 substituent group Chemical group 0.000 abstract description 3
- 229930182478 glucoside Natural products 0.000 abstract description 2
- 150000008131 glucosides Chemical class 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 101
- CSCPPACGZOOCGX-MICDWDOJSA-N 1-deuteriopropan-2-one Chemical compound [2H]CC(C)=O CSCPPACGZOOCGX-MICDWDOJSA-N 0.000 description 80
- 238000004896 high resolution mass spectrometry Methods 0.000 description 51
- 239000011734 sodium Substances 0.000 description 31
- 244000089409 Erythrina poeppigiana Species 0.000 description 21
- 235000009776 Rathbunia alamosensis Nutrition 0.000 description 21
- 229910004161 SiNa Inorganic materials 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 235000019439 ethyl acetate Nutrition 0.000 description 5
- 238000006206 glycosylation reaction Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 150000000700 C-glycosides Chemical class 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000012973 diazabicyclooctane Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 238000012746 preparative thin layer chromatography Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 125000002306 tributylsilyl group Chemical group C(CCC)[Si](CCCC)(CCCC)* 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IGRCWJPBLWGNPX-UHFFFAOYSA-N 3-(2-chlorophenyl)-n-(4-chlorophenyl)-n,5-dimethyl-1,2-oxazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N(C)C(=O)C1=C(C)ON=C1C1=CC=CC=C1Cl IGRCWJPBLWGNPX-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000000370 acceptor Substances 0.000 description 2
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229930182830 galactose Natural products 0.000 description 2
- 230000013595 glycosylation Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
- RUHJZSZTSCSTCC-UHFFFAOYSA-N 2-(bromomethyl)naphthalene Chemical compound C1=CC=CC2=CC(CBr)=CC=C21 RUHJZSZTSCSTCC-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- UPULOMQHYQDNNT-UHFFFAOYSA-N 5h-1,3-oxazol-2-one Chemical class O=C1OCC=N1 UPULOMQHYQDNNT-UHFFFAOYSA-N 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- REDUQXCPUSNJOL-UHFFFAOYSA-N C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O Chemical compound C(C1=CC=CC=C1)NC(CN(C(C1=CC=C(C=C1)C(C)C)=O)CC1=CC=C(C=C1)C(NO)=O)=O REDUQXCPUSNJOL-UHFFFAOYSA-N 0.000 description 1
- 238000003584 Ferrier rearrangement reaction Methods 0.000 description 1
- 102000002068 Glycopeptides Human genes 0.000 description 1
- 108010015899 Glycopeptides Proteins 0.000 description 1
- UGJBHEZMOKVTIM-UHFFFAOYSA-N N-formylglycine Chemical compound OC(=O)CNC=O UGJBHEZMOKVTIM-UHFFFAOYSA-N 0.000 description 1
- 230000004988 N-glycosylation Effects 0.000 description 1
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- KSCRVOKQPYZBHZ-IXPOFIJOSA-N benzyl n-[(2s)-1-[[(2s)-1-[[(2s)-1-(1,3-benzothiazol-2-yl)-1-oxo-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@H]1C(NCC1)=O)C(=O)C=1SC2=CC=CC=C2N=1)C(C)C)C(=O)OCC1=CC=CC=C1 KSCRVOKQPYZBHZ-IXPOFIJOSA-N 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000005517 carbenium group Chemical group 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- IRPXADUBAQAOKL-UHFFFAOYSA-N chembl1408927 Chemical compound C1=CC=C2C(N=NC3=C4C=CC(=CC4=CC(=C3O)S(O)(=O)=O)S(O)(=O)=O)=CC=C(S(O)(=O)=O)C2=C1 IRPXADUBAQAOKL-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 239000000386 donor Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000005858 glycosidation reaction Methods 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 150000002338 glycosides Chemical class 0.000 description 1
- 239000000937 glycosyl acceptor Substances 0.000 description 1
- 125000003147 glycosyl 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
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000000543 intermediate Substances 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
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- GQNZGCARKRHPOH-RQIKCTSVSA-N miocamycin Chemical compound C1[C@](OC(C)=O)(C)[C@@H](OC(=O)CC)[C@H](C)O[C@H]1O[C@H]1[C@H](N(C)C)[C@@H](O)[C@H](O[C@@H]2[C@H]([C@H](OC(=O)CC)CC(=O)O[C@H](C)C/C=C/C=C/[C@H](OC(C)=O)[C@H](C)C[C@@H]2CC=O)OC)O[C@@H]1C GQNZGCARKRHPOH-RQIKCTSVSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 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
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000144 pharmacologic effect Effects 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
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000725 suspension Substances 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
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- KTQKOGBTMNDCFG-UHFFFAOYSA-N tert-butyl(diphenyl)silicon Chemical compound C=1C=CC=CC=1[Si](C(C)(C)C)C1=CC=CC=C1 KTQKOGBTMNDCFG-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
Classifications
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- 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 System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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 System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/1892—Preparation; Treatments not provided for in C07F7/20 by reactions not provided for in C07F7/1876 - C07F7/1888
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Abstract
The invention belongs to the field of glucoside synthesis, and discloses chiral amino acid C-glucoside and a synthesis method thereof, wherein the chiral amino acid C-glucoside has a structure shown in a general formula I or an enantiomer and a diastereomer shown in the general formula I:
wherein P is selected from TBDPS, TBS, TIPS, ac, piv, bz, boc, bn, naphthylmethyl, TMS, TES, TBDMS, methyl, PMB, tr, MMT, DMT, MOM, BOM, MTM, THP, MEM, PMBOM, cbz, fmoc, R is selected from alkyl, phenyl, bn, PMB, -CH 2 CH 2 SMe and Ar are selected from phenyl, alkyl phenyl and halogenated phenyl. The invention uses 3, 4-cyclic carbonate-galactosyl sugar protected by a protecting group as a glycosyl donor, uses an amino acid precursor oxazoline-5-ketone as an acceptor, and the two react to obtain a C-glucoside compound with a novel skeleton, and the reaction has excellent beta-selectivity and high yield,Good enantioselectivity, mild reaction conditions and suitability for substrates of various substituent groups and protecting groups.
Description
Technical Field
The invention belongs to the field of glucoside synthesis, and particularly relates to chiral amino acid C-glucoside and a synthesis method thereof.
Background
Sugar chemistry is closely related to biochemistry and has been the focus of carbohydrate chemistry research. In this field, with the intensive research on carbohydrates and their conjugates in biochemical pathways, there is an increasing interest in glycosylation reactions that form glycosidic bonds. Studies have shown that C-glycosides have a higher metabolic stability compared to O-or N-type glycosidic linkages, and thus have good physicochemical and pharmacological properties. Many C-type glycoside natural products, including C-type glycosyl amino acid analogs and derivatized glycopeptides, have therapeutic uses.
On the other hand, in glycosylation reactions, steric control of the C-glycosidic bond is a difficult problem due to the lack of anomeric carbon effect and intramolecular aglycone transfer. Ferrier rearrangement of unsaturated glycosyl donors via carbenium intermediates is a classical method to construct anomeric carbon chiral centers and alpha-selectivity can often be achieved. Transition metal catalysis can be used to generate C-glycosyl linkages, particularly Heck-type glycosylation of saccharides.
The palladium-catalyzed decarboxylation reaction of saccharides and allyl carbonates opens up a practical way for selective glycosylation to obtain O-, N-or C-glycosides, and the reaction does not generally require the use of strong bases, which can increase substrate compatibility. For the synthesis of C-glycosides, the Zhokunkun team reacted arylboronic acids as nucleophiles with 3, 4-O-cyclic carbonate glycals, with steric guidance for the α -selective introduction of aryl groups.
In view of the foregoing, β -selective C-glycosylation remains a lack of effective methods and needs to be developed.
Disclosure of Invention
The invention aims to provide a chiral amino acid C-glycoside compound with a novel structure.
The invention also aims to provide a synthetic method of the compound.
In order to achieve one of the purposes, the invention adopts the following technical scheme:
a chiral amino acid C-glycoside having the structure of formula I or an enantiomer, diastereomer of formula I:
wherein P is selected from TBDPS, TBS, TIPS, ac, piv, bz, boc, bn, naphthylmethyl, TMS, TES, TBDMS, methyl, PMB, tr, MMT, DMT, MOM, BOM, MTM, THP, MEM, PMBOM, cbz, fmoc,
r is selected from alkyl, phenyl, bn, PMB, -CH 2 CH 2 SMe，
Ar is selected from phenyl, alkyl phenyl and halogenated phenyl.
Further, P is selected from TBDPS, TBS, TIPS, ac, piv, bz, boc, bn, naphthylmethyl, TMS, TES, TBDMS, PMB, MOM.
Further, the P is selected from TBDPS, TBS, TIPS, ac, piv, bz, boc, bn, naphthylmethyl.
Further, R is selected from (C1-C4) alkyl, phenyl, bn, PMB and-CH 2 CH 2 SMe。
Further, R is selected from methyl, isopropyl, sec-butyl, isobutyl, phenyl, bn, PMB, -CH 2 CH 2 SMe。
Further, ar is selected from phenyl, (C1-C4) alkyl substituted phenyl, fluorophenyl, chlorophenyl, bromophenyl.
Further, ar is selected from phenyl, methylphenyl, ethylphenyl, fluorophenyl, chlorophenyl and bromophenyl.
Further, ar is selected from phenyl, methylphenyl and bromophenyl.
Further, ar is selected from phenyl, p-methylphenyl, m-methylphenyl and p-bromophenyl.
Further, the chiral amino acid C-glycoside is selected from the following compounds or their enantiomers, diastereomers:
a method for synthesizing chiral amino acid C-glucoside comprises the following steps: in the presence of a palladium catalyst, compound 1 and compound 2 react as follows:
further, the palladium catalyst is selected from Pd (OAc) 2 、Pd(PPh 3 ) 4 、Pd(acac) 2 、Pd 2 (dba) 3 、[Pd(allyl)Cl] 2 。
Further, the reaction adds a ligand selected from the following compounds:
further, the amount of the palladium catalyst is at least 1mol%.
Further, the ligand is used in an amount of at least 2mol%.
The amount of the palladium catalyst, ligand used is based on the amount of compound 1, for example, the amount of the palladium catalyst is written in the form of 5mol%, which means that 0.05mol of the palladium catalyst is used per 1mol of compound 1; the amount of ligand used is written in the form of 7.5mol%, meaning that 0.075mol of ligand is used per 1mol of compound 1.
Further, the molar ratio of compound 1 to compound 2 is 1: (1-3).
Further, the reaction takes dichloromethane, dichloroethane, chloroform, tetrahydrofuran or acetonitrile as a solvent.
Further, the temperature of the reaction is 25 ℃ or higher.
Further, the reaction time is more than 0.5 h.
Further, DABCO was added to the reaction in an amount of 120mol%.
TMS means trimethylsilyl; TES refers to triethylsilyl; TBDMS refers to tert-butyl dimethyl silicon base; TBDPS refers to tert-butyl diphenyl silicon base; TBS means tert-butyl dimethylsilyl group; TIPS refers to triisopropylsilyl groups.
Bn represents a benzyl group; PMB refers to p-methoxybenzyl; tr means trityl; MMT means p-methoxytrityl; DMT refers to dimethoxytrityl; MOM is methoxymethyl; BOM means benzyloxymethyl; MTM refers to thiomethyl; THP means tetrahydropyranyl; MEM means 2-methoxyethoxymethyl; PMBOM refers to p-methoxybenzyloxymethyl.
Ac means acetyl; piv means pivaloyl; bz is benzoyl; boc means tert-butoxycarbonyl; cbz means benzyloxycarbonyl; fmoc refers to 9-fluorenylmethoxycarbonyl; naphthylmethyl refers to
DABCO refers to 1, 4-diazabicyclo [2.2.2] octane; TBAF means tetra-n-butylammonium fluoride; EDCI refers to 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide.
As used herein, "alkyl" refers to a saturated aliphatic hydrocarbon group which is a straight or branched chain group containing 1 to 20 carbon atoms, preferably an alkyl group containing 1 to 12 carbon atoms, more preferably an alkyl group containing 1 to 6 carbon atoms. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, isopentyl, neopentyl, hexyl, 2-hexyl, 3-methylpentyl.
The invention has the following beneficial effects:
the invention uses 3, 4-cyclic carbonate-galactosyl sugar protected by a protecting group as a glycosyl donor, uses an amino acid precursor oxazoline-5-ketone as an acceptor, and the two react to obtain a C-glucoside compound with a novel framework, and the reaction has excellent beta-selectivity, high yield, good enantioselectivity and mild reaction conditions, and is suitable for substrates of various substituent groups and protecting groups.
Detailed Description
All solvents and reagents were purchased from commercial products and no further purification was required unless otherwise indicated. Thin Layer Chromatography (TLC) using 60GF254 silica gel plate; the silica gel column chromatography uses Qingdao marine silica gel (60, the particle size is 0.040-0.063 mm); TLC color development was performed using UV light (254, 365nm). 1 H and 13 c nuclear magnetic resonance spectroscopy 400 Mm using Bruker DPXOr Bruker DPX500 Mr NMR instrument, the solvent is DMSO-d 6 、CDCl 3 Or acetone-d 6 Tetramethylsilane (TMS) is used as an internal standard; chemical shifts are in ppm and coupling constants are in Hz. In that 1 In HNMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, p represents quintet, m represents multiplet, br represents broad. 13 Data for C nuclear magnetic resonance are reported in units of chemical shifts δ (ppm). High Resolution Mass Spectrometry (HRMS) analysis was performed using Q-exact (Thermo Scientific).
Example 1
Synthesis of a substrate
Compounds 1a-1h are according to [ (a) Dai, y ]; tian, B.; chen, h.; zhang, q.acs Catalysis 2019,9,2909-2915; (b) Dai, y; zheng, j.; zhang, q.organic Letters 2018,20,3923-3927; (c) Meng, s.; zhong, w.; yao, w.; li, Z. organic Letters 2020,22,2981-2986.
Compound 1i was prepared as follows:
according to literature [ Dai, y ]; zheng, j.; zhang, Q.organic Letters 2018,20,3923-3927, prepares s-1i.
The carbonate derivative s-1i (226mg, 1.3mmol) was slowly treated with sodium hydride (78mg, 1.95mmol) in anhydrous DMF (2 mL) at 0 deg.C (ice bath). After 10 min, 2- (bromomethyl) -naphthalene (431mg, 1.95mmol) was added and the resulting mixture was stirred at room temperature overnight. Complete consumption of the starting material was detected by TLC chromatography. The reaction mixture was cooled to 0 ℃ with NH 4 Aqueous Cl was quenched and then extracted with EtOAc (10 mL. Times.2), and the combined organic phases were washed with water (15 mL) and brine (15 mL). The separated organic phase is passed over Na 2 SO 4 Drying and concentrating to obtain crude productThe product was purified by silica gel column chromatography (EtOAc/petroleum ether = 1/3) to give galactose donor 1i as a white powder (yield 62%).
1 H NMR(400MHz,CDCl 3 )δ7.86–7.83(m,3H),7.78(s,1H),7.51–7.44(m,3H),6.68(d,J＝6.3Hz,1H),5.15(ddd,J＝7.7,3.1,1.1Hz,1H),4.96–4.91(m,2H),4.75(t,J＝12.4Hz,2H),4.10(td,J＝6.7,1.6Hz,1H),3.88–3.78(m,2H)； 13 C NMR(100MHz,CDCl 3 )δ154.0,149.2,134.6,133.2,133.1,128.4,127.9,127.7,126.8,126.3,126.1,125.6,98.0,73.9,73.2,72.5,68.8,68.0；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 18 H 16 O 5 Na,335.0895; found 335.0891.
Preparing oxazolinone derivative 2 [ a) Badiola, e ] according to literature procedures; fisher, b.; g. Lolo mez-Bengoa, E.; mielgo, a.; olaizola, i.; urrouzuno, i.; garcia, j.m.; odiozola, j.m.; razkin, j.; oiarbide, m.; palomo, C.journal of the American Chemical Society 2014,136,17869-17881; (b) Gerwick, W.H.; fenic, W.the Journal of Organic Chemistry 1983,48,3325-3329; de Mello, a.c.; momo, p.b.; burtoloso, a.c.b.; amarante, G.W. the Journal of Organic Chemistry 2018,83, 11399-11406.
Step 1, synthesizing N-benzoyl amino acid. The corresponding natural amino acid (40mmol, 1equiv) was slowly dissolved in 2N NaOH (50mL, 100mmol, 2.5equiv) at 0 ℃ and benzoyl chloride (1.05 equiv) was added dropwise at this temperature. After the addition was complete, the mixture was stirred at 0 ℃ for a further 30 minutes. Subsequently, the mixture was allowed to warm to room temperature or 75 ℃ and stirred for two more hours. After cooling to 0 ℃ with an ice bath, the reaction mixture was acidified with 6N HCl to give a white precipitate. The mixture was held at 0 ℃ for one hour after which the solid was collected, washed with cold water and air dried without further purification and the crude was used in the next step.
Step 2, synthesizing oxazoline ketone derivative 2. To the anhydrous CH of N-benzoylamino acid (10 mmol) at room temperature 2 Cl 2 To the suspension (30 mL) was added EDCI-HCl (2.5g, 13mmol, 1.3equiv). The reaction mixture was washed with water (20 mL) and brine (20 mL), then Na 2 SO 4 And (5) drying. The solvent was removed under reduced pressure to give the crude product, which was purified by silica gel column chromatography to give the product. The patterns of compounds 2a-2g are consistent with literature reports.
Compound 2h: 1 H NMR(400MHz,CDCl 3 )δ7.92(d,J＝7.9Hz,2H),7.31(d,J＝8.0Hz,2H),4.30(d,J＝4.4Hz,1H),2.45(s,3H),2.45–2.36(m,1H),1.16(d,J＝6.9Hz,3H),1.04(d,J＝6.9Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ178.0,161.7,143.4,129.5,127.8,123.1,70.6,31.2,21.7,18.7,17.5；HRMS(ESI)m/z:[M+H]accurate mass calculation C 13 H 16 NO 2 218.1181; found 218.1177.
Compound 2i: 1 H NMR(400MHz,CDCl 3 )δ7.91–7.88(m,2H),7.29(d,J＝8.4Hz,2H),4.40(dz,J＝3.9Hz,0.54H),4.35(d,J＝4.3Hz,0.46H),2.43(s,3H),2.18–2.08(m,1H),1.74–1.33(m,2H),1.17–0.90(m,6H)； 13 C NMR(100MHz,CDCl 3 )δ178.7,177.9,161.7,161.6,143.3,129.5,129.5,127.8,127.8,123.1,69.7,69.1,37.7,26.2,25.0,21.7,15.4,14.4,11.8,11.7；HRMS(ESI)m/z:[M+H]accurate mass calculation C 14 H 18 NO 2 232.1338; found 232.1332.
Compound 2j: 1 H NMR(400MHz,CDCl 3 )δ7.88(d,J＝8.3Hz,2H),7.28(d,J＝8.0Hz,2H),4.40(dd,J＝8.9,5.7Hz,1H),2.43(s,3H),2.11–2.01(m,1H),1.83(ddd,J＝13.6,7.8,5.7Hz,1H),1.71–1.64(m,1H),1.03(d,J＝6.7Hz,3H),1.01(d,J＝6.7Hz,3H)； 13 C NMR(100MHz,CDCl 3 )δ179.2,161.4,143.3,129.5,127.8,123.2,63.9,40.8,25.2,22.7,22.0,21.7；HRMS(ESI)m/z:[M+H]accurate mass calculation C 14 H 18 NO 2 232.1338; found 232.1333.
Compound 2k: 1 H NMR(400MHz,CDCl 3 )δ7.88(d,J＝8.0Hz,2H),7.29(d,J＝8.0Hz,2H),4.58(dd,J＝7.2,5.8Hz,1H),2.73(t,J＝7.1Hz,2H),2.43(s,3H),2.30(dtd,J＝14.1,7.0,5.8Hz,1H),2.18–2.09(m,4H)； 13 C NMR(100MHz,CDCl 3 )δ178.6,162.1,143.5,129.5,127.9,123.0,63.6,30.5,30.0,21.7,15.1；HRMS(ESI)m/z:[M+H]accurate mass calculation C 13 H 16 NO 2 S,250.0902; found 250.0897.
Example 2
The inventors contemplate the use of amino acids as the glycal acceptor, which is more complex to control than the C-glycosyl acceptors used in the prior art, due to the possible O-or N-glycosylation of amino acids. The inventor takes 6-O-TBDPS-3, 4-cyclic carbonate-galactosyl sugar 1a as glycosyl donor and 4-benzyl-2-p-methylphenyl oxazoline-5-ketone 2a as amino acid precursor to optimize reaction conditions.
a: the reaction conditions are as follows: 1a (0.1 mmol), 2a (1.2 equiv) and [ Pd ]]Catalyst (5 mol%), ligand (7.5 mol%) and solvent (2 mL) were reacted at room temperature for 12 hours in yield 1 H NMR determination using Ph 3 CH as internal standard. b: the reaction time was 2 hours. c: the reaction time was 0.5 hour.
Screening for phosphine ligand, L1 formed diastereomers b- (R) -3a and b- (S) -3a in a ratio of 36 to 64, with an overall yield of 91%, and good b-selectivityAnd (4) selectivity. Screening of the Palladium catalyst, pd (acac) 2 Dr can be increased to 31:69, the total yield is 96%, if only Pd (PPh) is used 3 ) 4 Without the use of ligand, the overall yield drops to 48%. Screening the solvent in CH 2 Cl 2 Compared to other solvents, no significant improvement was achieved. When the reaction time was reduced to 2 hours, the dr of b-3a was 31.5.
1 H NMR(400MHz,acetone-d 6 )δ7.76–7.70(m,6H),7.45–7.37(m,6H),7.27(d,J＝7.9Hz,2H),7.20–7.12(m,5H),6.26(ddd,J＝10.4,5.7,2.0Hz,1H),6.08(dd,J＝10.3,1.5Hz,1H),4.60(d,J＝2.0Hz,1H),4.00–3.93(m,2H),3.87–3.79(m,2H),3.42(d,J＝13.5Hz,1H),3.31(d,J＝13.5Hz,1H),3.22(d,J＝9.5Hz,1H),2.36(s,3H),0.99(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.5,161.4,144.3,136.3,136.3,135.4,134.4,134.2,131.9,131.2,130.5,130.2,128.8,128.6,128.5,127.8,123.7,79.6,78.0,77.6,64.5,62.4,39.5,27.1,21.5,19.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 39 H 41 NO 5 SiNa,654.2652; found 654.2662.
1 H NMR(400MHz,acetone-d 6 )δ7.76–7.71(m,6H),7.46–7.38(m,6H),7.30–7.27(m,2H),7.21–7.11(m,5H),6.30(ddd,J＝10.2,5.8,2.0Hz,1H),6.14(dd,J＝10.3,1.8Hz,1H),4.70(d,J＝1.9Hz,1H),3.96(ddt,J＝7.5,5.7,1.7Hz,1H),3.90–3.79(m,3H),3.40(d,J＝13.3Hz,1H),3.31(d,J＝13.3Hz,1H),2.84(d,J＝9.9Hz,1H),2.37(s,3H),1.04(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.9,162.0,144.4,136.3,136.2,135.1,134.3,134.1,131.8,131.8,131.2,130.5,130.3,128.8,128.6,128.5,128.5,127.9,127.8,123.7,79.3,78.0,77.8,64.5,62.4,39.5,27.1,21.5,19.7.；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 39 H 41 NO 5 SiNa,654.2652; found 654.2660.
The general synthetic method comprises the following steps:
pd (acac) was added to a sealed Schlenk tube equipped with a magnetic stir bar under an argon atmosphere 2 (1.5mg, 5mol%), ligand L1 (4.1mg, 7.5mol%), compound 1 (0.1 mmol), compound 2 (0.12 mmol). Then adding anhydrous CH 2 Cl 2 (2 mL), the resulting mixture was degassed and fill-degassed three times. The reaction mixture was stirred at room temperature and monitored by TLC until compound 1 was completely consumed in two hours. The solvent was removed under reduced pressure to give the crude product, which was purified by preparative TLC (EtOAc/petroleum ether) to give the products β - (R) -3 and β - (S) -3. For substrate 2g, 2h, 2i, 1.2 equivalents of DABCO were additionally added.
The subsequent development of the substrate is carried out, the methyl group of the phenyl group at the C2 position of compound 2 is in the ortho position, which has no effect on the yield, and the yield is reduced by replacing the methyl group with bromine. No substituent group is arranged on the benzene ring, and the yield and the dr value are not obviously influenced. The benzyl group at C4 position of compound 2 was changed to p-methoxybenzyl group with no change in dr ratio (31); by conversion to isobutyl and-CH 2 CH 2 SMe, reduced diastereoselectivity. These glycosidation reactions all show absolute β -selectivity. The inventors continued to investigate the effect of the protecting group for the hydroxyl group at position 6 of the galactan 1 on the reaction. In addition to the TBDPS group, the other silicon-based analogues TBS, TIPS, did not have any effect on the reaction and improved yields were obtained with similar diastereoselectivities. Ac and Piv protected galactose in high yield (94% and 98%), dr values identical (36. Benzoyl and Boc protecting groups were also tolerated with a minor adverse effect on diastereoselectivity (42,the yield was very good (89%), the dr value was medium (35).
Example 3
1 H NMR(400MHz,acetone-d 6 )δ7.75(dd,J＝7.4,1.8Hz,2H),7.71–7.69(m,2H),7.65–7.62(m,2H),7.45–7.31(m,8H),7.22–7.11(m,5H),6.28(ddd,J＝10.3,5.7,2.0Hz,1H),6.14(dd,J＝10.3,1.6Hz,1H),4.61(d,J＝2.2Hz,1H),4.00–3.92(m,2H),3.87–3.78(m,2H),3.41(d,J＝13.5Hz,1H),3.34(d,J＝13.5Hz,1H),3.08(d,J＝9.2Hz,1H),2.33(s,3H),0.98(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.5,161.4,139.4,136.3,136.3,135.4,134.4,134.2,134.1,131.9,131.2,130.5,130.5,129.5,128.9,128.8,128.6,127.9,126.5,125.7,79.6,78.1,77.7,64.5,62.4,39.5,27.0,21.1,19.6；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 39 H 41 NO 5 SiNa,654.2652; found 654.2658.
1 H NMR(400MHz,acetone-d 6 )δ7.76–7.73(m,4H),7.65–7.63(m,2H),7.44–7.34(m,8H),7.22–7.14(m,5H),6.30(ddd,J＝10.3,5.8,1.9Hz,1H),6.15(dd,J＝10.3,1.6Hz,1H),4.70(d,J＝2.0Hz,1H),3.99–3.95(m,1H),3.91–3.79(m,3H),3.41(d,J＝13.3Hz,1H),3.32(d,J＝13.3Hz,1H),2.81(d,J＝9.9Hz,1H),2.35(s,3H),1.04(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.9,162.0,139.5,136.3,136.3,135.1,134.4,134.3,134.2,131.8,131.2,130.5,130.5,129.6,128.9,128.8,128.6,128.6,127.9,127.8,126.5,125.7,79.4,78.1,77.9,64.6,62.4,39.5,27.1,21.1,19.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 39 H 41 NO 5 SiNa,654.2652; found 654.2657.
Example 4
1 H NMR(400MHz,acetone-d 6 )δ7.76–7.64(m,8H),7.45–7.36(m,6H),7.21–7.11(m,5H),6.27(ddd,J＝10.4,5.6,2.0Hz,1H),6.16(dd,J＝10.3,1.5Hz,1H),4.62(d,J＝2.2Hz,1H),4.00–3.91(m,2H),3.88–3.75(m,2H),3.42(d,J＝13.5Hz,1H),3.35(d,J＝13.5Hz,1H),3.13(d,J＝9.0Hz,1H),0.97(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.1,160.6,136.3,136.3,135.2,134.3,134.1,132.9,131.9,131.1,130.5,130.5,130.2,128.8,128.5,127.9,127.7,127.7,125.7,79.7,77.9,77.8,64.6,62.4,39.4,27.0,19.6；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 38 H 38 BrNO 5 SiNa,718.1600; found 718.1602.
1 H NMR(400MHz,acetone-d 6 )δ7.77–7.68(m,8H),7.46–7.38(m,6H),7.20–7.12(m,5H),6.29(ddd,J＝10.4,5.7,1.9Hz,1H),6.18(dd,J＝10.2,1.6Hz,1H),4.70(d,J＝2.0Hz,1H),3.98–3.95(m,1H),3.89–3.77(m,3H),3.43(d,J＝13.4Hz,1H),3.31(d,J＝13.4Hz,1H),2.87(d,J＝8.8Hz,1H),1.03(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.5,161.2,136.3,136.3,135.0,134.3,134.1,133.0,131.8,131.2,130.5,130.3,128.8,128.6,128.6,128.0,127.9,127.7,125.7,79.5,78.3,77.9,64.6,62.4,39.5,27.1,19.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 38 H 38 BrNO 5 SiNa,718.1600; found 718.1602.
Example 5
1 H NMR(400MHz,acetone-d 6 )δ7.85–7.82(m,2H),7.76–7.69(m,4H),7.59–7.55(m,1H),7.48–7.36(m,8H),7.22–7.10(m,5H),6.27(ddd,J＝10.3,5.7,2.1Hz,1H),6.13(dd,J＝10.3,1.7Hz,1H),4.62(d,J＝1.9Hz,1H),4.00–3.92(m,2H),3.88–3.79(m,2H),3.43(d,J＝13.5Hz,1H),3.34(d,J＝13.5Hz,1H),3.17(d,J＝9.3Hz,1H),0.98(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ178.0,162.0,159.7,144.4,136.3,136.3,134.3,134.2,132.3,131.8,130.5,130.3,128.6,128.6,128.5,127.8,126.8,123.8,114.1,79.3,78.2,77.8,64.5,62.4,55.3,38.7,27.1,21.5,19.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 38 H 39 NO 5 SiNa,640.2495; found 640.2502.
1 H NMR(400MHz,acetone-d 6 )δ7.84(dd,J＝8.0,1.4Hz,2H),7.76–7.73(m,4H),7.62–7.58(m,1H),7.50–7.38(m,8H),7.22–7.13(m,5H),6.30(ddd,J＝10.3,5.7,2.0Hz,1H),6.16(dd,J＝10.2,1.6Hz,1H),4.70(d,J＝1.9Hz,1H),3.97(ddd,J＝9.8,5.7,1.7Hz,1H),3.91–3.80(m,3H),3.43(d,J＝13.3Hz,1H),3.32(d,J＝13.3Hz,1H),2.85(d,J＝9.8Hz,1H),1.04(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.8,161.9,136.3,136.3,135.1,134.3,134.1,133.6,131.8,131.2,130.5,130.5,129.6,128.8,128.6,128.5,128.5,127.9,127.8,126.6,79.4,78.1,77.8,64.6,62.4,39.5,27.1,19.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 38 H 39 NO 5 SiNa,640.2495; found 640.2499.
Example 6
1 H NMR(400MHz,acetone-d 6 )δ7.76–7.70(m,6H),7.47–7.37(m,6H),7.27(d,J＝8.0Hz,2H),7.11(d,J＝8.3Hz,2H),6.72(d,J＝8.5Hz,2H),6.26(ddd,J＝10.3,5.7,2.0Hz,1H),6.07(dd,J＝10.3,1.6Hz,1H),4.58(d,J＝2.2Hz,1H),3.99–3.93(m,2H),3.89–3.75(m,2H),3.66(s,3H),3.35(d,J＝13.7Hz,1H),3.25(d,J＝13.7Hz,1H),3.18(d,J＝9.5Hz,1H),2.36(s,3H),1.00(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.6,161.4,159.7,144.3,136.3,136.3,134.4,134.1,132.2,131.8,130.5,130.5,130.2,128.6,128.5,127.9,127.0,123.8,114.1,79.5,78.0,77.8,64.5,62.4,55.3,38.7,27.1,21.5,19.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 40 H 43 NO 6 SiNa,684.2757; found 684.2765.
1 H NMR(400MHz,acetone-d 6 )δ7.76–7.72(m,6H),7.46–7.38(m,6H),7.30–7.28(m,2H),7.11–7.09(m,2H),6.71(d,J＝8.3Hz,2H),6.30(ddd,J＝10.5,5.9,2.0Hz,1H),6.13(dd,J＝10.4,1.6Hz,1H),4.67(s,1H),3.98–3.94(m,1H),3.90–3.79(m,3H),3.66(s,3H),3.33(d,J＝13.5Hz,1H),3.25(d,J＝13.5Hz,1H),2.83(d,J＝10.1Hz,1H),2.37(s,3H),1.05(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ178.0,162.0,159.7,144.4,136.3,136.3,134.3,134.2,132.3,131.8,130.5,130.3,128.6,128.6,128.5,127.8,126.8,123.8,114.1,79.3,78.2,77.8,64.5,62.4,55.3,38.7,27.1,21.5,19.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 40 H 43 NO 6 SiNa,684.2757; found 684.2761.
Example 7
1 H NMR(400MHz,acetone-d 6 )δ7.92(d,J＝8.1Hz,2H),7.78–7.75(m,2H),7.70–7.68(m,2H),7.63–7.61(m,2H),7.49–7.33(m,11H),6.19(ddd,J＝10.3,5.8,2.2Hz,1H),5.63(dd,J＝10.3,1.6Hz,1H),4.83(d,J＝2.0Hz,1H),3.93(ddt,J＝7.5,5.8,1.8Hz,1H),3.85(dd,J＝8.9,4.1Hz,1H),3.78–3.71(m,2H),2.68(d,J＝9.4Hz,1H),2.39(s,3H),0.93(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ176.2,161.7,144.5,136.3,136.3,135.4,134.3,134.0,131.9,130.5,130.3,129.6,129.5,128.8,128.6,128.5,127.7,127.2,123.9,79.9,79.4,78.4,64.3,62.2,27.0,21.6,19.6；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 38 H 39 NO 5 SiNa,640.2495; found 640.2505.
1 H NMR(400MHz,acetone-d 6 )δ7.97(d,J＝8.0Hz,2H),7.80–7.78(m,2H),7.72–7.68(m,4H),7.49–7.37(m,11H),6.19(ddd,J＝10.2,5.8,1.9Hz,1H),5.60(dd,J＝10.4,1.7Hz,1H),5.01(d,J＝2.0Hz,1H),3.95–3.90(m,1H),3.87–3.80(m,2H),3.74–3.70(m,1H),2.81(d,J＝9.4Hz,1H),2.43(s,3H),1.02(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.6,162.4,144.7,136.2,136.2,135.8,134.3,134.0,131.3,130.5,130.4,130.4,129.6,129.6,128.8,128.6,128.5,127.2,127.1,123.9,80.7,79.4,77.3,64.5,62.1,27.1,21.6,19.6；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 38 H 39 NO 5 SiNa,640.2495; found 640.2498.
Example 8
1 H NMR(400MHz,acetone-d 6 )δ7.85(d,J＝8.0Hz,2H),7.73–7.70(m,2H),7.67–7.65(m,2H),7.46–7.32(m,8H),6.24(ddd,J＝10.3,5.7,2.1Hz,1H),6.05(dd,J＝10.3,1.6Hz,1H),4.45(d,J＝2.0Hz,1H),3.97–3.93(m,1H),3.90–3.85(m,1H),3.77–3.72(m,2H),2.89(d,J＝9.4Hz,1H),2.39(s,3H),1.56(s,3H),0.96(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ178.7,161.3,144.2,136.3,136.3,134.3,134.1,131.6,130.5,130.5,130.2,128.6,128.5,127.8,124.2,79.3,78.6,72.8,64.3,62.3,27.0,21.5,19.8,19.6；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 33 H 37 NO 5 SiNa,578.2339; found 578.2342.
1 H NMR(400MHz,acetone-d 6 )δ7.85(d,J＝7.9Hz,2H),7.72–7.69(m,4H),7.45–7.34(m,8H),6.27(ddd,J＝10.4,5.8,1.9Hz,1H),6.13(dd,J＝10.2,1.7Hz,1H),4.53(d,J＝2.0Hz,1H),3.96–3.91(m,1H),3.83–3.76(m,2H),3.73–3.67(m,1H),2.73(d,J＝9.8Hz,1H),2.41(s,3H),1.56(s,3H),1.01(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ179.5,161.8,144.3,136.3,136.2,134.3,134.1,131.4,130.5,130.3,128.6,128.6,128.5,127.6,124.2,79.1,78.5,72.8,64.4,62.3,27.1,21.6,19.7,19.6；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 33 H 38 NO 5 Si,556.2519; found 556.2519.
Example 9
1 H NMR(400MHz,acetone-d 6 )δ7.87(d,J＝8.0Hz,2H),7.70–7.68(m,2H),7.65–7.63(m,2H),7.45–7.32(m,8H),6.24(ddd,J＝10.4,5.7,2.1Hz,1H),6.03(dd,J＝10.3,1.5Hz,1H),4.66(d,J＝2.0Hz,1H),3.94–3.90(m,1H),3.86–3.79(m,1H),3.76–3.70(m,2H),2.75(d,J＝9.6Hz,1H),2.49(hept,J＝7.1Hz,1H),2.39(s,3H),1.09(d,J＝6.8Hz,3H),0.94(s,9H),0.90(d,J＝6.7Hz,3H)； 13 C NMR(100MHz,acetone-d 6 )δ178.5,161.8,144.3,136.3,134.3,134.0,131.9,130.5,130.3,128.7,128.5,127.2,123.9,80.2,79.4,76.5,64.4,62.4,32.1,27.0,21.5,19.6,17.3,17.0；HRMS(ESI)m/z:[M+Na]Precise qualityQuantity calculation C 35 H 41 NO 5 SiNa,606.2652; found 606.2658.
1 H NMR(400MHz,acetone-d 6 )δ7.89(d,J＝8.0Hz,2H),7.76–7.73(m,4H),7.48–7.38(m,8H),6.25(ddd,J＝10.2,5.9,1.9Hz,1H),5.85(dd,J＝10.2,1.7Hz,1H),4.74(d,J＝1.9Hz,1H),3.94–3.78(m,4H),2.61(hept,J＝7.1Hz,1H),2.57(d,J＝10.4Hz,1H),2.43(s,3H),1.07–1.04(m,12H),0.96(d,J＝6.8Hz,3H)； 13 C NMR(100MHz,acetone-d 6 )δ178.7,162.4,144.6,136.3,136.3,134.3,134.2,132.2,130.5,130.5,128.7,128.6,127.7,123.7,79.7,79.2,75.3,64.5,62.3,31.7,27.1,21.6,19.7,17.1,16.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 35 H 41 NO 5 SiNa,606.2652; found 606.2656.
Example 10
1 H NMR(400MHz,acetone-d 6 )δ7.87(d,J＝7.9Hz,2H),7.69–7.67(m,2H),7.63–7.60(m,2H),7.43–7.31(m,8H),6.26(ddd,J＝10.4,5.8,2.0Hz,1H),6.09(d,J＝10.4Hz,1H),4.68(d,J＝2.0Hz,1H),3.91(dd,J＝9.1,6.3Hz,1H),3.84–3.77(m,1H),3.73–3.67(m,2H),2.59(d,J＝9.7Hz,1H),2.38(s,3H),2.18(ddt,J＝10.4,7.0,3.5Hz,1H),1.12–1.00(m,5H),0.92–0.86(m,12H)； 13 C NMR(100MHz,acetone-d 6 )δ178.9,161.6,144.2,136.2,134.3,134.0,131.9,130.5,130.3,128.6,128.5,128.5,127.1,124.0,80.9,79.3,76.5,64.3,62.4,38.9,27.0,24.9,21.5,19.6,13.2,11.9；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 36 H 43 NO 5 SiNa,620.2808; found 620.2814.
1 H NMR(400MHz,acetone-d 6 )δ7.88(d,J＝8.0Hz,2H),7.74–7.72(m,4H),7.45–7.37(m,8H),6.26(ddd,J＝10.2,5.9,1.9Hz,1H),5.90(dd,J＝10.2,1.7Hz,1H),4.81(d,J＝2.0Hz,1H),3.91(dd,J＝10.4,6.0Hz,1H),3.86–3.80(m,3H),2.57(d,J＝10.5Hz,1H),2.43(s,3H),2.33(dqd,J＝10.1,7.0,3.1Hz,1H),1.68(dqd,J＝15.0,7.4,2.9Hz,1H),1.19(ddd,J＝13.4,10.4,7.1Hz,1H),1.03(s,9H),0.99(d,J＝6.9Hz,3H),0.89(t,J＝7.4Hz,3H)； 13 C NMR(100MHz,acetone-d 6 )δ178.6,162.4,144.6,136.3,136.3,134.2,134.1,132.1,130.5,130.4,128.6,128.6,128.6,127.7,123.7,79.8,79.1,75.3,64.5,62.3,38.0,27.1,23.8,21.6,19.6,12.7,11.9；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 36 H 43 NO 5 SiNa,620.2808; found 620.2812.
Example 11
1 H NMR(400MHz,acetone-d 6 )δ7.88(d,J＝8.0Hz,2H),7.72–7.69(m,2H),7.66–7.64(m,2H),7.46–7.32(m,8H),6.23(ddd,J＝10.3,5.7,2.1Hz,1H),6.03(dd,J＝10.4,1.1Hz,1H),4.46(d,J＝2.3Hz,1H),3.93(dd,J＝8.9,6.1Hz,1H),3.85(dt,J＝9.9,5.0Hz,1H),3.76–3.70(m,2H),2.83(d,J＝9.4Hz,1H),2.39(s,3H),2.14(dd,J＝14.0,4.9Hz,1H),1.83(dd,J＝14.0,8.0Hz,1H),1.68–1.59(m,1H),0.95(s,9H),0.91(d,J＝6.7Hz,3H),0.82(d,J＝6.6Hz,3H)； 13 C NMR(100MHz,acetone-d 6 )δ179.1,161.3,144.3,136.3,136.3,134.3,134.0,131.8,130.5,130.5,130.3,128.6,128.5,127.6,124.1,79.3,78.9,76.2,64.3,62.3,42.1,27.0,25.4,24.4,23.0,21.5,19.6；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 36 H 43 NO 5 SiNa,620.2808; found 620.2808.
1 H NMR(400MHz,acetone-d 6 )δ7.87(d,J＝8.0Hz,2H),7.73–7.71(m,4H),7.45–7.36(m,8H),6.24(ddd,J＝10.4,5.8,1.9Hz,1H),6.06(dd,J＝10.3,1.6Hz,1H),4.50(d,J＝2.0Hz,1H),3.93–3.89(m,1H),3.83–3.71(m,3H),2.68(d,J＝9.8Hz,1H),2.42(s,3H),2.08(dd,J＝14.1,6.0Hz,1H),1.92(dd,J＝14.1,6.6Hz,1H),1.64–1.55(m,1H),1.02(s,9H),0.88(d,J＝6.6Hz,3H),0.85(d,J＝6.6Hz,3H)； 13 C NMR(100MHz,acetone-d 6 )δ179.4,161.9,144.5,136.3,136.3,134.3,134.1,131.6,130.5,130.4,128.6,128.6,128.5,127.9,124.0,79.2,78.7,76.6,64.4,62.3,42.0,27.1,25.5,24.2,23.6,21.6,19.6；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 36 H 43 NO 5 SiNa,620.2808; found 620.2814.
Example 12
1 H NMR(400MHz,acetone-d 6 )δ7.88(d,J＝8.0Hz,2H),7.73–7.71(m,2H),7.68–7.66(m,2H),7.46–7.32(m,8H),6.24(ddd,J＝10.3,5.8,2.1Hz,1H),6.02(dd,J＝10.7,1.7Hz,1H),4.50(d,J＝2.0Hz,1H),3.96–3.92(m,1H),3.90–3.85(m,1H)3.79–3.71(m,2H),2.97(d,J＝9.3Hz,1H),2.58–2.51(m,1H),2.46–2.28(m,6H),2.00(s,3H),0.97(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ178.4,162.3,144.4,136.3,136.3,134.3,134.1,131.9,130.5,130.5,130.3,128.7,128.5,127.5,124.1,79.4,78.3,75.5,64.3,62.3,32.4,29.2,27.0,21.6,19.6,14.8；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 35 H 41 NO 5 SSiNa,638.2372; found 638.2374.
1 H NMR(400MHz,acetone-d 6 )7.87(d,J＝8.0Hz,2H),7.74–7.72(m,4H),7.46–7.35(m,8H),6.25(ddd,J＝10.4,5.7,1.9Hz,1H),6.06(dd,J＝10.3,1.6Hz,1H),4.57(d,J＝2.0Hz,1H),3.95–3.91(m,1H),3.86–3.73(m,3H),2.75(d,J＝9.7Hz,1H),2.55–2.48(m,1H),2.44–2.31(m,6H),2.01(s,3H),1.03(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ178.8,162.7,144.5,136.3,136.3,134.3,134.1,131.8,130.5,130.4,128.7,128.6,128.5,127.7,124.0,79.3,78.1,76.0,64.4,62.3,32.7,28.9,27.1,21.6,19.6,14.9；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 35 H 41 NO 5 SSiNa,638.2372; found 638.2377.
Example 13
1 H NMR(400MHz,acetone-d 6 )δ7.73(d,J＝8.0Hz,2H),7.30(d,J＝8.0Hz,2H),7.21–7.10(m,5H),6.27(ddd,J＝10.4,5.8,2.0Hz,1H),6.11(dd,J＝10.2,1.6Hz,1H),4.59(d,J＝2.1Hz,1H),3.93–3.89(m,1H),3.85(dd,J＝10.5,5.6Hz,1H),3.72(dd,J＝10.5,6.3Hz,1H),3.61(ddd,J＝7.1,4.0,1.5Hz,1H),3.40(d,J＝13.4Hz,1H),3.33(d,J＝13.5Hz,1H),2.99(d,J＝9.4Hz,1H),2.38(s,3H),0.84(s,9H),0.00(s,6H)； 13 C NMR(100MHz,acetone-d 6 )δ177.6,161.3,144.3,135.3,132.0,131.2,130.2,128.8,128.5,127.8,127.7,123.8,79.6,78.0,77.7,63.7,62.2,39.6,26.2,21.5,18.8,-5.1,-5.4；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 29 H 37 NO 5 SiNa,530.2339; found 530.2342.
1 H NMR(400MHz,acetone-d 6 )δ7.73(d,J＝8.1Hz,2H),7.31(d,J＝8.0Hz,2H),7.21–7.12(m,5H),6.30(ddd,J＝10.3,5.9,1.9Hz,1H),6.13(dd,J＝10.2,1.7Hz,1H),4.66(d,J＝2.0Hz,1H),3.90–3.86(m,1H),3.77(dd,J＝10.1,5.6Hz,1H),3.71–3.62(m,2H),3.40(d,J＝13.3Hz,1H),3.28(d,J＝13.3Hz,1H),2.69(d,J＝10.0Hz,1H),2.39(s,3H),0.89(s,9H),0.06(s,3H),0.05(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ177.9,162.0,144.4,135.1,131.9,131.2,130.3,128.8,128.5,127.9,127.7,123.8,79.2,78.1,77.8,63.5,62.1,39.5,26.2,21.5,18.8,-5.2,-5.4；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 29 H 38 NO 5 Si,508.2519; found 508.2517.
Example 14
1 H NMR(400MHz,acetone-d 6 )δ7.72(d,J＝8.0Hz,2H),7.30(d,J＝8.0Hz,2H),7.21–7.10(m,5H),6.28(ddd,J＝10.4,5.8,2.0Hz,1H),6.08(dd,J＝10.3,1.6Hz,1H),4.61(d,J＝2.0Hz,1H),3.98–3.93(m,2H),3.83(dd,J＝10.2,6.2Hz,1H),3.66(td,J＝6.0,1.7Hz,1H),3.42(d,J＝13.4Hz,1H),3.32(d,J＝13.5Hz,1H),3.02(d,J＝9.5Hz,1H),2.38(s,3H),1.11–0.97(m,21H)； 13 C NMR(100MHz,acetone-d 6 )δ177.6,161.3,144.3,135.3,132.0,131.2,130.2,128.8,128.5,127.8,127.7,123.8,79.7,78.1,77.8,64.0,62.3,39.6,21.5,18.3,12.6；HRMS(ESI)m/z:[M+Na]Accurate mass calculation C 32 H 43 NO 5 SiNa,572.2808; found 572.2813.
1 H NMR(400MHz,acetone-d 6 )δ7.73(d,J＝8.1Hz,2H),7.31(d,J＝7.9Hz,2H),7.21–7.12(m,5H),6.31(ddd,J＝10.3,5.9,1.9Hz,1H),6.13(dd,J＝10.2,1.7Hz,1H),4.68(d,J＝2.0Hz,1H),3.94–3.85(m,2H),3.79(dd,J＝10.1,6.2Hz,1H),3.69(td,J＝6.1,1.6Hz,1H),3.40(d,J＝13.3Hz,1H),3.29(d,J＝13.3Hz,1H),2.73(d,J＝10.1Hz,1H),2.39(s,3H),1.15–1.01(m,21H)； 13 C NMR(100MHz,acetone-d 6 )δ177.9,162.0,144.4,135.2,132.0,131.2,130.3,128.8,128.5,127.9,127.7,123.8,79.3,78.1,77.8,63.9,62.2,39.5,21.5,18.3,18.3,12.6；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 32 H 44 NO 5 Si,550.2989(ii) a Found 550.2993.
Example 15
1 H NMR(400MHz,acetone-d 6 )δ7.74(d,J＝8.3Hz,2H),7.31(d,J＝7.8Hz,2H),7.22–7.11(m,5H),6.24(ddd,J＝10.3,5.6,2.1Hz,1H),6.12(dd,J＝10.3,1.7Hz,1H),4.54(d,J＝2.0Hz,1H),4.30(dd,J＝11.6,7.6Hz,1H),4.16(dd,J＝11.6,4.7Hz,1H),3.93(ddt,J＝7.7,5.7,2.1Hz,1H),3.80(ddd,J＝7.2,4.7,2.2Hz,1H),3.51(d,J＝9.2Hz,1H),3.39(d,J＝13.5Hz,1H),3.34(d,J＝13.5Hz,1H),2.39(s,3H),1.89(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ177.3,170.8,161.5,144.3,135.3,131.4,131.2,130.2,128.8,128.5,127.8,127.8,123.8,77.7,77.4,76.7,64.3,62.3,39.2,21.5,20.6；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 25 H 26 NO 6 436.1760; found 436.1763.
1 H NMR(400MHz,acetone-d 6 )δ7.74(d,J＝8.0Hz,2H),7.31(d,J＝7.9Hz,2H),7.23–7.13(m,5H),6.26(ddd,J＝10.3,5.7,1.9Hz,1H),6.14(dd,J＝10.3,1.6Hz,1H),4.63(d,J＝2.2Hz,1H),4.21–4.12(m,2H),3.92–3.88(m,1H),3.82(ddd,J＝7.0,4.8,1.8Hz,1H),3.42(d,J＝13.3Hz,1H),3.27(d,J＝13.3Hz,1H),3.08(d,J＝9.6Hz,1H),2.39(s,3H),2.01(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ177.1,170.0,161.2,143.6,134.3,130.5,130.4,129.5,128.0,127.7,127.1,127.0,123.0,77.1,76.7,75.7,63.6,61.5,38.7,20.7,19.9；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 25 H 26 NO 6 436.1760; found 436.1757.
Example 16
1 H NMR(400MHz,acetone-d 6 )δ7.73(d,J＝8.0Hz,2H),7.30(d,J＝7.9Hz,2H),7.29–7.11(m,5H),6.25(ddd,J＝10.4,5.5,2.0Hz,1H),6.14(dd,J＝10.3,1.5Hz,1H),4.55(d,J＝2.1Hz,1H),4.28(dd,J＝11.3,7.7Hz,1H),4.18(dd,J＝11.6,4.5Hz,1H),3.96–3.92(m,1H),3.82(ddd,J＝7.2,4.5,2.0Hz,1H),3.46(d,J＝9.2Hz,1H),3.40(d,J＝13.5Hz,1H),3.33(d,J＝13.5Hz,1H),2.38(s,3H),1.08(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.3,176.5,160.6,143.4,134.5,130.6,130.3,129.4,128.0,127.7,127.0,123.0,77.1,76.7,76.0,63.6,61.6,38.5,38.3,26.4,20.7；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 28 H 31 NO 6 Na,500.2049; found 500.2053.
1 H NMR(400MHz,acetone-d 6 )δ7.72(d,J＝8.0Hz,2H),7.30(d,J＝7.9Hz,2H),7.21–7.12(m,5H),6.27(ddd,J＝10.4,5.6,1.9Hz,1H),6.18(dd,J＝10.3,1.5Hz,1H),4.65(d,J＝2.1Hz,1H),4.21(dd,J＝11.5,7.5Hz,1H),4.14(dd,J＝11.5,4.7Hz,1H),3.91(ddd,J＝9.5,5.3,2.2Hz,1H),3.85(ddd,J＝7.1,4.7,1.8Hz,1H),3.41(d,J＝13.3Hz,1H),3.28(d,J＝13.3Hz,1H),3.10(d,J＝9.6Hz,1H),2.38(s,3H),1.19(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ178.1,177.8,161.9,144.4,135.1,131.3,131.2,130.3,128.8,128.5,127.9,127.9,123.8,77.9,77.8,76.6,64.3,62.4,39.4,39.2,27.4,21.5；HRMS(ESI)m/z:[M+Na]Accurate mass calculation of C 28 H 31 NO 6 Na,500.2049; found 500.2050.
Example 17
1 H NMR(400MHz,acetone-d 6 )δ7.91(d,J＝7.5Hz,2H),7.71(d,J＝8.0Hz,2H),7.63–7.59(m,1H),7.45(t,J＝7.7Hz,2H),7.26(d,J＝8.0Hz,2H),7.21–7.10(m,5H),6.28(ddd,J＝10.5,5.5,2.0Hz,1H),6.19(dd,J＝10.4,1.4Hz,1H),4.59(d,J＝2.0Hz,1H),4.55–4.47(m,2H),4.06(ddd,J＝9.4,5.1,2.4Hz,1H),3.99(ddd,J＝7.3,4.9,2.1Hz,1H),3.57(d,J＝9.0Hz,1H),3.37(t,J＝13.9Hz,2H),2.38(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ177.3,166.5,161.5,144.2,135.3,133.7,131.4,131.2,131.1,130.2,130.1,129.2,128.8,128.4,127.9,127.8,123.8,77.8,77.4,76.8,65.0,62.4,39.2,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 30 H 28 NO 6 498.1917; found 498.1921.
1 H NMR(400MHz,acetone-d 6 )δ8.06(d,J＝8.3Hz,2H),7.74(d,J＝8.0Hz,2H),7.65(t,J＝7.4Hz,1H),7.52(t,J＝7.7Hz,2H),7.30(d,J＝7.9Hz,2H),7.22–7.12(m,5H),6.30(ddd,J＝10.5,5.5,1.9Hz,1H),6.18(dd,J＝10.3,1.6Hz,1H),4.68(d,J＝2.0Hz,1H),4.49(dd,J＝11.6,4.6Hz,1H),4.42(dd,J＝11.5,7.4Hz,1H),4.04–4.01(m,2H),3.44(d,J＝13.3Hz,1H),3.27(d,J＝13.4Hz,1H),3.22(d,J＝9.6Hz,1H),2.38(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ177.9,166.6,162.0,144.4,135.1,133.9,131.3,131.3,131.1,130.3,130.2,129.3,128.7,128.5,127.9,127.9,123.8,77.9,77.6,76.6,65.1,62.5,39.5,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation of C 30 H 28 NO 6 498.1917; found 498.1919.
Example 18
1 H NMR(400MHz,acetone-d 6 )δ7.73(d,J＝7.9Hz,2H),7.31(d,J＝7.9Hz,2H),7.22–7.11(m,5H),6.25(ddd,J＝10.5,5.6,2.0Hz,1H),6.10(dd,J＝10.3,1.5Hz,1H),4.58(d,J＝2.2Hz 1H),4.28(dd,J＝11.5,7.5Hz,1H),4.20(dd,J＝11.5,4.2Hz,1H),3.94(ddd,J＝8.8,5.5,2.5Hz,1H),3.82(ddd,J＝7.0,4.1,1.9Hz,1H),3.46(d,J＝9.2Hz,1H),3.40(d,J＝13.5Hz,1H),3.33(d,J＝13.5Hz,1H),2.38(s,3H),1.38(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.4,161.4,154.2,144.3,135.3,131.4,131.2,130.3,128.8,128.5,127.9,127.8,123.8,81.9,77.7,77.5,76.7,67.3,62.4,39.4,27.8,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 28 H 32 NO 7 494.2179; found 494.2182.
1 H NMR(400MHz,acetone-d 6 )δ7.74(d,J＝7.9Hz,2H),7.31(d,J＝7.9Hz,2H),7.25–7.10(m,5H),6.27(ddd,J＝9.9,5.5,1.6Hz,1H),6.13(dd,J＝10.3,1.2Hz,1H),4.64(d,J＝2.1Hz,1H),4.21(dd,J＝11.6,7.4Hz,1H),4.15(dd,J＝11.5,4.3Hz,1H),3.92–3.88(m,1H),3.85–3.81(m,1H),3.41(d,J＝13.3Hz,1H),3.28(d,J＝13.3Hz,1H),3.03(d,J＝9.8Hz,1H),2.39(s,3H),1.45(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ177.9,162.1,154.2,144.4,135.1,131.3,131.3,130.3,128.8,128.5,127.9,127.8,123.8,82.0,77.9,77.4,76.5,67.2,62.4,39.5,27.8,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 28 H 32 NO 7 494.2179; found 494.2182.
Example 19
1 H NMR(400MHz,acetone-d 6 )δ7.77–7.74(m,2H),7.30(d,J＝8.0Hz,2H),7.27–7.11(m,10H),6.25(ddd,J＝10.3,5.6,2.1Hz,1H),6.16(dd,J＝10.4,1.6Hz,1H),4.58(q,J＝1.9Hz,1H),4.53(d,J＝12.4Hz,1H),4.46(d,J＝12.3Hz,1H),3.91(d,J＝6.6Hz,1H),3.79(ddd,J＝6.7,4.5,2.1Hz,1H),3.74(dd,J＝10.6,4.5Hz,1H),3.60(dd,J＝10.6,6.9Hz,1H),3.39(q,J＝13.4Hz,1H),3.35(q,J＝13.5Hz,1H),3.16(d,J＝9.1Hz,1H),2.39(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ177.5,161.3,144.3,139.9,135.4,131.7,131.2,130.3,128.9,128.8,128.5,128.0,127.9,127.8,127.7,123.9,78.7,77.9,77.6,73.7,70.9,62.7,39.3,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 30 H 30 NO 5 484.2124; found 484.2127.
1 H NMR(400MHz,acetone-d 6 )δ7.73(d,J＝8.3Hz,2H),7.37–7.12(m,12H),6.27(ddd,J＝10.3,5.8,2.0Hz,1H),6.14(dd,J＝10.3,1.7Hz,1H),4.67(q,J＝1.9Hz,1H),4.55(s,2H),3.88(ddt,J＝9.6,5.8,1.9Hz,1H),3.82(ddd,J＝6.8,4.8,1.9Hz,1H),3.66(dd,J＝10.4,4.9Hz,1H),3.56(dd,J＝10.4,6.8Hz,1H),3.42(d,J＝13.3Hz,1H),3.28(d,J＝13.3Hz,1H),2.82(d,J＝9.8Hz,1H),2.38(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ178.1,161.9,144.4,139.8,135.2,131.7,131.2,130.3,129.0,128.8,128.5,128.2,128.0,127.9,127.7,123.8,78.1,78.0,77.7,73.5,70.6,62.6,39.5,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation of C 30 H 30 NO 5 484.2124; found 484.2127.
Example 20
1 H NMR(400MHz,acetone-d 6 )δ7.86–7.81(m,2H),7.77–7.74(m,3H),7.70(s,1H),7.50–7.44(m,2H),7.33(dd,J＝8.5,1.7Hz,1H),7.28(d,J＝8.0Hz,2H),7.23–7.11(m,5H),6.26(ddd,J＝10.3,5.6,2.1Hz,1H),6.18(dd,J＝10.3,1.6Hz,1H),4.71(dd,J＝12.6,0.9Hz,1H),4.63(dd,J＝12.6,0.9Hz,1H),4.59(q,J＝1.9Hz,1H),3.94(ddt,J＝9.2,5.5,1.9Hz,1H),3.85–3.79(m,2H),3.70–3.64(m,1H),3.38(s,2H),3.19(d,J＝9.1Hz,1H),2.36(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ177.5,161.3,144.3,137.6,135.4,134.2,133.7,131.7,131.2,130.3,128.8,128.6,128.5,128.5,128.4,127.8,127.7,126.7,126.4,126.4,126.4,123.9,78.8,77.9,77.6,73.9,71.0,62.7,39.3,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 34 H 32 NO 5 534.2280; found 534.2286.
1 H NMR(400MHz,acetone-d 6 )δ7.89–7.84(m,4H),7.70(d,J＝8.3Hz,2H),7.52–7.45(m,3H),7.27–7.11(m,7H),6.27(ddd,J＝10.3,5.7,2.0Hz,1H),6.15(dd,J＝10.3,1.6Hz,1H),4.75–4.71(m,2H),4.69(q,J＝1.8Hz,1H),3.92–3.84(m,2H),3.70(dd,J＝10.5,4.6Hz,1H),3.60(dd,J＝10.5,6.8Hz,1H),3.42(d,J＝13.3Hz,1H),3.29(d,J＝13.3Hz,1H),2.84(d,J＝9.8Hz,1H),2.35(s,3H)； 13 C NMR(100MHz,acetone-d 6 )δ178.1,161.9,144.4,137.4,135.2,134.2,133.8,131.7,131.2,130.3,128.8,128.7,128.6,128.5,128.4,127.9,127.7,126.8,126.7,126.5,126.5,123.8,78.1,78.0,77.8,73.5,70.7,62.7,39.5,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 34 H 32 NO 5 534.2280; found 534.2281.
Example 20
To demonstrate the utility of the obtained β -C-glycoside, alcoholysis and deprotection of β - (R) -3a were carried out in 85% and 82% yields, respectively, to give β - (R) -5a. The same reaction on β - (S) -3a gives the corresponding C-glycoside β - (S) -5a, which contains a quaternary carbon stereocenter with opposite chirality to β - (R) -5a.
Under an argon atmosphere, a dried, sealed Schlenk tube equipped with a magnetic stir bar was charged with β - (R) -3a or β - (S) -3a (63mg, 0.1 mmol) and anhydrous MeOH (1 mL). MeONa (27. Mu.L, 0.15mmol,30% in MeOH) was then added and the reaction mixture stirred at room temperature for 20 min. After completion of the reaction (monitored by TLC), H was used 2 The mixture was diluted O (15 mL) and extracted with EtOAc (10 mL. Times.2). For combined organic phasesWashing with brine, na 2 SO 4 Dried and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give β - (R) -4a (85% yield) or β - (S) -4a (79% yield), respectively.
1 H NMR(400MHz,acetone-d 6 )δ7.79–7.77(m,4H),7.66(d,J＝8.3Hz,2H),7.51(s,1H),7.48–7.40(m,6H),7.30–7.27(m,2H),7.22–7.16(m,5H),6.35(dd,J＝10.5,1.5Hz,1H),6.02(ddd,J＝10.4,5.6,2.2Hz,1H),4.73(d,J＝1.9Hz,1H),3.98–3.97(m,2H),3.92(ddt,J＝7.7,5.7,1.9Hz,1H),3.82–3.74(m,5H),3.50(d,J＝13.0Hz,1H),3.14(d,J＝7.8Hz,1H),2.32(s,3H),1.04(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ171.2,167.3,142.2,136.6,136.3,134.3,134.2,133.0,131.2,130.7,130.5,130.5,129.6,129.2,128.9,128.6,128.0,127.6,79.7,76.3,67.1,65.2,62.6,52.2,39.0,27.2,21.3,19.6；HRMS(ESI)m/z:[M+H]Accurate mass calculation of C 40 H 46 NO 6 Si,664.3094; found 664.3093.
1 H NMR(400MHz,acetone-d 6 )δ7.89–7.84(m,4H),7.71(d,J＝7.9Hz,2H),7.52–7.48(m,6H),7.41(s,1H),7.29–7.23(m,4H),7.18–7.14(m,3H),6.24(d,J＝10.4Hz,1H),6.04(ddd,J＝10.3,5.5,2.1Hz,1H),4.58(d,J＝2.2Hz,1H),4.11–3.92(m,4H),3.84–3.81(m,1H),3.72(s,3H),3.67(d,J＝13.6Hz,1H),3.20(d,J＝8.1Hz,1H),2.37(s,3H),1.12(s,9H)； 13 C NMR(100MHz,acetone-d 6 )δ171.4,167.3,142.5,137.7,136.3,136.3,134.3,134.2,132.9,131.6,130.6,130.5,130.1,129.7,128.8,128.7,128.0,127.2,80.4,76.0,66.8,65.4,62.7,52.4,35.9,27.2,21.3,19.7；HRMS(ESI)m/z:[M+H]Accurate mass calculation of C 40 H 46 NO 6 Si,664.3094; found 664.3091.
TBAF (1.2 eq.,0.5M in THF) was added to a solution of β - (R) -4a (63 mg) or β - (S) -4a (48 mg) in THF at room temperature, and the reaction mixture was stirred for 15 minutes. After completion of the reaction (monitored by TLC), the mixture was concentrated under reduced pressure to give the crude product, which was purified by preparative TLC to give β - (R) -5a (82% yield) or β - (S) -5a (84% yield), respectively.
1 H NMR(400MHz,CDCl 3 )δ7.59(d,J＝8.2Hz,2H),7.22–7.19(m,5H),7.13(s,1H),7.10–7.08(m,2H),6.20(dd,J＝10.4,1.4Hz,1H),6.14(ddd,J＝10.3,5.5,2.0Hz,1H),4.98(d,J＝1.9Hz,1H),3.90(t,J＝7.1Hz,1H),3.82–3.70(m,6H),3.57–3.52(m,2H),2.64(s,1H),2.37(s,3H),2.36(s,1H)； 13 C NMR(100MHz,CDCl 3 )δ171.3,167.6,142.2,135.5,132.0,130.1,129.3,129.3,128.4,128.3,127.1,127.0,77.2,75.8,68.2,62.9,62.8,52.6,36.9,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 24 H 28 NO 6 426.1917; found 426.1913.
1 H NMR(400MHz,CDCl 3 )δ7.57(d,J＝8.1Hz,2H),7.26–7.18(m,5H),7.12–7.09(m,2H),7.01(s,1H),6.15(ddd,J＝10.3,5.7,2.1Hz,1H),6.05(dd,J＝10.2,1.5Hz,1H),5.15(d,J＝1.8Hz,1H),4.08(d,J＝13.8Hz,1H),3.93(dd,J＝11.3,6.4Hz,2H),3.83–3.82(m,4H),3.71(ddd,J＝6.7,4.7,1.6Hz,1H),3.57(d,J＝13.8Hz,1H),2.39(s,3H),2.16(s,1H),1.99(d,J＝9.7Hz,1H)； 13 C NMR(100MHz,CDCl 3 )δ171.8,167.1,142.4,135.9,131.9,130.0,129.4,129.1,129.0,128.3,127.0,126.9,77.6,76.1,68.3,62.8,53.1,35.4,21.5；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 24 H 28 NO 6 426.1917; found 426.1913.
When beta- (R) -3a and beta- (S) -3a olefin is dihydroxylated, the hydroxyl newly formed at the C3 position can carry out nucleophilic ring opening on an oxazole-5 (4H) -ketone ring to obtain a lacto-glucoside product, and the stereochemical structure (beta- (R) -6a, beta- (S) -6 a) can be reserved. The beta- (S) -6a is subjected to X-ray crystal diffraction (CCDC 2201062) to determine the spatial configuration thereof.
To beta- (R) -3a (63mg, 0.1mmol) or beta- (S) -3a (63mg, 0.1mmol) in acetone/H at room temperature 2 O (1 mL/0.2mL,5 2 OsO 4 ·2H 2 O (1.8mg, 5mol%) and NMO (35mg, 0.3mmol), and the reaction mixture was stirred for 24 hours. After completion of the reaction (monitored by TLC), the mixture was extracted with EtOAc (5 mL. Times.2), and the combined organic phases were washed with brine, na 2 SO 4 And (5) drying. The solvent was removed under reduced pressure and then purified by preparative TLC to give β - (R) -6a (92% yield) or β - (S) -6a (90% yield), respectively.
1 H NMR(400MHz,CDCl 3 )δ7.62–7.56(m,4H),7.49(d,J＝8.0Hz,2H),7.45–7.34(m,4H),7.29–7.22(m,7H),7.07(d,J＝7.9Hz,2H),6.30(s,1H),4.73(dd,J＝9.8,2.4Hz,1H),4.47(s,1H),4.31–4.28(m,2H),4.10(d,J＝3.7Hz,1H),3.95–3.86(m,3H),3.50(d,J＝13.9Hz,1H),3.30(d,J＝13.9Hz,1H),3.16(brs,1H),2.31(s,3H),0.94(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ171.9,166.7,142.5,135.5,135.4,134.3,132.5,132.0,130.5,130.3,130.1,130.0,129.3,128.6,127.9,127.9,127.6,127.1,76.6,75.9,75.7,72.6,66.7,65.4,60.0,41.3,26.6,21.5,19.1；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 39 H 44 NO 7 Si,666.2887; found 666.2887.
1 H NMR(400MHz,CDCl 3 )δ7.78–7.76(m,2H),7.71–7.68(m,2H),7.47–7.32(m,13H),7.14–7.12(m,2H),6.34(s,1H),5.28(d,J＝10.3Hz,1H),4.59(dd,J＝10.3,2.5Hz,1H),4.51–4.49(m,1H),4.23(d,J＝3.6Hz,1H),4.13(dd,J＝11.2,4.0Hz,1H),4.06–3.98(m,2H),3.83(s,1H),3.52(d,J＝14.1Hz,1H),3.30(d,J＝14.1Hz,1H),2.33(s,3H),2.04(s,1H),1.08(s,9H)； 13 C NMR(100MHz,CDCl 3 )δ172.7,166.8,142.5,135.7,135.5,133.1,132.3,132.2,130.9,130.3,130.0,130.0,129.2,128.9,128.0,127.9,127.9,126.9,75.7,74.2,72.8,67.3,65.6,62.0,34.2,26.7,21.4,19.1；HRMS(ESI)m/z:[M+H]Accurate mass calculation C 39 H 44 NO 7 Si,666.2887; found 666.2884.
The absolute configuration of the compound beta- (S) -6a is determined by X-ray diffraction analysis, and relevant data can be obtained at Cambridge crystallography data center (www.ccdc.cam.ac.uk/contacts/retrieving.html), the storage number is CCDC 2201062, and the detailed information is shown in the following table:
example 21
Amplification experiments, with reference to general synthesis methods, 6-O-TBDPS-3, 4-cyclic carbonate-galactan 1a was used in an amount of 10mmol, 4-benzyl-2-p-methylphenyl oxazoline-5-one 2a was used in an amount of 12mmol, and Pd (acac) was used as a catalyst 2 The amount used was 1mol%, the amount of the ligand L1 was 2mol%, the isolation yield of β - (R) -3a was 27%, and the isolation yield of β - (S) -3a was 20%.
The above description is only for the specific embodiments of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are also within the scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.
Claims (10)
1. A chiral amino acid C-glycoside having the structure of formula I or an enantiomer, diastereomer of formula I:
wherein P is selected from TBDPS, TBS, TIPS, ac, piv, bz, boc, bn, naphthylmethyl, TMS, TES, TBDMS, methyl, PMB, tr, MMT, DMT, MOM, BOM, MTM, THP, MEM, PMBOM, cbz, fmoc,
r is selected from alkyl, phenyl, bn, PMB, -CH 2 CH 2 SMe，
Ar is selected from phenyl, alkyl phenyl and halogenated phenyl.
2. The chiral amino acid C-glycoside according to claim 1, wherein P is selected from TBDPS, TBS, TIPS, ac, piv, bz, boc, bn, naphthylmethyl.
3. The chiral amino acid C-glycoside according to claim 1, wherein R is selected from (C1-C4) alkyl, phenyl, bn, PMB, -CH 2 CH 2 SMe。
4. The chiral amino acid C-glycoside according to claim 3, wherein R is selected from methyl, isopropyl, sec-butyl, isobutyl, phenyl, bn, PMB, -CH 2 CH 2 SMe。
5. The chiral amino acid C-glycoside according to claim 1, wherein Ar is selected from phenyl, (C1-C4) alkyl substituted phenyl, fluorophenyl, chlorophenyl, bromophenyl.
6. The chiral amino acid C-glycoside according to claim 5, wherein Ar is selected from the group consisting of phenyl, p-methylphenyl, m-methylphenyl, p-bromophenyl.
7. Chiral amino acid C-glycoside according to claim 1, characterized in that it is selected from the following compounds or their enantiomers, diastereomers:
8. a method for synthesizing a chiral amino acid C-glycoside according to any one of claims 1 to 7, comprising the steps of: in the presence of a palladium catalyst, compound 1 and compound 2 react as follows:
the P, ar and R are defined in any one of claims 1 to 7.
9. The legal method according to claim 8, characterized in that a ligand is added, which is selected from the following compounds:
10. the legal process according to claim 8 or 9, characterized in that the palladium catalyst is chosen from Pd (OAc) 2 、Pd(PPh 3 ) 4 、Pd(acac) 2 、Pd 2 (dba) 3 、[Pd(allyl)Cl] 2 (ii) a The palladium catalyst is used in an amount of at least 1molPercent; the amount of the ligand is at least 2mol%; the molar ratio of the compound 1 to the compound 2 is 1: (1-3); the reaction takes dichloromethane, dichloroethane, chloroform, tetrahydrofuran or acetonitrile as a solvent; the reaction temperature is above 25 ℃, and the reaction time is above 0.5 h.
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| WO2022123501A1 (en) * | 2020-12-10 | 2022-06-16 | Victoria Link Limited | Protected deoxydidehydro-nucleosides |
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