C56H97NO12Si2
Tacrolimus
Conditions | Yield |
---|---|
With hydrogen fluoride In acetonitrile at 20℃; for 0.05h; | 100% |
With hydrogen fluoride; acetonitrile In dichloromethane at 0℃; for 0.0833333h; | 81% |
With hydrogen fluoride In acetonitrile at 20℃; | 81% |
24,33-Bis-(t.butyl-dimethylsilyl)-FK 506
Tacrolimus
Conditions | Yield |
---|---|
With hydrogen fluoride In acetonitrile at 50℃; for 0.2h; | 100% |
With hydrogen fluoride In acetonitrile at 20℃; for 2.5h; |
14-<(tert-butyldimethylsilyl)oxy>-24,32-bis<(triisopropylsilyl)oxy>-FK506
Tacrolimus
Conditions | Yield |
---|---|
With hydrogen fluoride In acetonitrile for 18h; Ambient temperature; | 73% |
C66H101NO11Si2
Tacrolimus
Conditions | Yield |
---|---|
With hydrogen fluoride; 3,3-dimethyldioxirane 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h; Yield given. Multistep reaction; |
C66H101NO12Si2
Tacrolimus
Conditions | Yield |
---|---|
With hydrogen fluoride In acetonitrile at 20℃; for 10h; Cyclization; desilylation; | 10.5 mg |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1: 46 percent / epichlorohydrin / 1,2-dichloro-benzene / 0.05 h / 140 °C 2: 100 percent / aq. HF / acetonitrile / 0.2 h / 50 °C View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1: 43 percent / epichlorohydrin / 1,2-dichloro-benzene / 0.05 h / 140 °C 2: 100 percent / aq. HF / acetonitrile / 0.05 h / 20 °C View Scheme |
C69H107NO12Si2
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1: 100 percent / dimethyl dioxirane / acetone / 2.17 h / -50 - -26 °C 2: 10.5 mg / aq. HF / acetonitrile / 10 h / 20 °C View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 3 steps 1: 110 percent / C8K-ZnCl2-AgOAc / tetrahydrofuran / 1 h / 0 °C 2: 100 percent / dimethyl dioxirane / acetone / 2.17 h / -50 - -26 °C 3: 10.5 mg / aq. HF / acetonitrile / 10 h / 20 °C View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 4 steps 1: 88 percent / triphenylphosphine; imidazole; iodine / toluene / 0.5 h / 70 °C 2: 110 percent / C8K-ZnCl2-AgOAc / tetrahydrofuran / 1 h / 0 °C 3: 100 percent / dimethyl dioxirane / acetone / 2.17 h / -50 - -26 °C 4: 10.5 mg / aq. HF / acetonitrile / 10 h / 20 °C View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 5 steps 1: 92 percent / DDQ / CH2Cl2; H2O / 0.83 h / 20 °C 2: 88 percent / triphenylphosphine; imidazole; iodine / toluene / 0.5 h / 70 °C 3: 110 percent / C8K-ZnCl2-AgOAc / tetrahydrofuran / 1 h / 0 °C 4: 100 percent / dimethyl dioxirane / acetone / 2.17 h / -50 - -26 °C 5: 10.5 mg / aq. HF / acetonitrile / 10 h / 20 °C View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 6 steps 1: 21.0 mg / Et3N; methyl-2-chloropyridinium iodide / CH2Cl2 / 14 h / 20 °C 2: 92 percent / DDQ / CH2Cl2; H2O / 0.83 h / 20 °C 3: 88 percent / triphenylphosphine; imidazole; iodine / toluene / 0.5 h / 70 °C 4: 110 percent / C8K-ZnCl2-AgOAc / tetrahydrofuran / 1 h / 0 °C 5: 100 percent / dimethyl dioxirane / acetone / 2.17 h / -50 - -26 °C 6: 10.5 mg / aq. HF / acetonitrile / 10 h / 20 °C View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 6 steps 1: 81 percent / Dess-Martin periodinane / CH2Cl2 / 3 h / Ambient temperature 2: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 3: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 4: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 5: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 6: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 3 steps 1: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 2: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 3: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 4 steps 1: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 2: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 3: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 4: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 6 steps 1: 47.3 mg / 2-chloro-1-methylpyridinium iodide, NET3 / CH2Cl2 / 6 h / Heating 2: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 3: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 4: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 5: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 6: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 7 steps 1: 1) 2-chloro-1-methylpyridinium iodide, NEt3, 2) NEt3 / 1) CH2Cl2, reflux, 17 h, 2) EtOH, 5 h 2: 81 percent / Dess-Martin periodinane / CH2Cl2 / 3 h / Ambient temperature 3: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 4: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 5: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 6: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 7: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 5 steps 1: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 2: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 3: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 4: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 5: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 12 steps 1: NaHCO3, KBr, 4-methoxy-2,2,6,6-tetramethylpiperidinyloxy free radical, NaOCl / CH2Cl2 / 1.33 h / 0 °C 2: NaH2PO4, NaClO2 / 2-methyl-propan-2-ol; H2O; various solvent(s) / 2 h 3: 495 mg / diethyl ether 4: Dess-Martin periodinane / CH2Cl2 / 1 h 5: LiOH*H2O / tetrahydrofuran / 0.5 h 6: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1h, 2) THF, 0 deg C, 1 h 7: 47.3 mg / 2-chloro-1-methylpyridinium iodide, NET3 / CH2Cl2 / 6 h / Heating 8: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 9: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 10: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 11: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 12: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme | |
Multi-step reaction with 10 steps 1: NaHCO3, KBr, 4-methoxy-2,2,6,6-tetramethylpiperidinyloxy free radical, NaOCl / CH2Cl2 / 1.33 h / 0 °C 2: NaH2PO4, NaClO2 / 2-methyl-propan-2-ol; H2O; various solvent(s) / 2 h 3: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1 h, 2) THF, 0 deg C, 1 h 4: 1) 2-chloro-1-methylpyridinium iodide, NEt3, 2) NEt3 / 1) CH2Cl2, reflux, 17 h, 2) EtOH, 5 h 5: 81 percent / Dess-Martin periodinane / CH2Cl2 / 3 h / Ambient temperature 6: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 7: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 8: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 9: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 10: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 2: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 11 steps 1: NaH2PO4, NaClO2 / 2-methyl-propan-2-ol; H2O; various solvent(s) / 2 h 2: 495 mg / diethyl ether 3: Dess-Martin periodinane / CH2Cl2 / 1 h 4: LiOH*H2O / tetrahydrofuran / 0.5 h 5: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1h, 2) THF, 0 deg C, 1 h 6: 47.3 mg / 2-chloro-1-methylpyridinium iodide, NET3 / CH2Cl2 / 6 h / Heating 7: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 8: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 9: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 10: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 11: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme | |
Multi-step reaction with 9 steps 1: NaH2PO4, NaClO2 / 2-methyl-propan-2-ol; H2O; various solvent(s) / 2 h 2: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1 h, 2) THF, 0 deg C, 1 h 3: 1) 2-chloro-1-methylpyridinium iodide, NEt3, 2) NEt3 / 1) CH2Cl2, reflux, 17 h, 2) EtOH, 5 h 4: 81 percent / Dess-Martin periodinane / CH2Cl2 / 3 h / Ambient temperature 5: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 6: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 7: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 8: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 9: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 7 steps 1: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1h, 2) THF, 0 deg C, 1 h 2: 47.3 mg / 2-chloro-1-methylpyridinium iodide, NET3 / CH2Cl2 / 6 h / Heating 3: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 4: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 5: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 6: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 7: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 10 steps 1: 495 mg / diethyl ether 2: Dess-Martin periodinane / CH2Cl2 / 1 h 3: LiOH*H2O / tetrahydrofuran / 0.5 h 4: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1h, 2) THF, 0 deg C, 1 h 5: 47.3 mg / 2-chloro-1-methylpyridinium iodide, NET3 / CH2Cl2 / 6 h / Heating 6: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 7: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 8: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 9: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 10: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme | |
Multi-step reaction with 8 steps 1: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1 h, 2) THF, 0 deg C, 1 h 2: 1) 2-chloro-1-methylpyridinium iodide, NEt3, 2) NEt3 / 1) CH2Cl2, reflux, 17 h, 2) EtOH, 5 h 3: 81 percent / Dess-Martin periodinane / CH2Cl2 / 3 h / Ambient temperature 4: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 5: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 6: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 7: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 8: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 9 steps 1: LiOH*H2O / tetrahydrofuran; H2O / 5 h / Ambient temperature 2: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1 h, 2) THF, 0 deg C, 1 h 3: 1) 2-chloro-1-methylpyridinium iodide, NEt3, 2) NEt3 / 1) CH2Cl2, reflux, 17 h, 2) EtOH, 5 h 4: 81 percent / Dess-Martin periodinane / CH2Cl2 / 3 h / Ambient temperature 5: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 6: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 7: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 8: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 9: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme | |
Multi-step reaction with 9 steps 1: Dess-Martin periodinane / CH2Cl2 / 1 h 2: LiOH*H2O / tetrahydrofuran / 0.5 h 3: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1h, 2) THF, 0 deg C, 1 h 4: 47.3 mg / 2-chloro-1-methylpyridinium iodide, NET3 / CH2Cl2 / 6 h / Heating 5: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 6: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 7: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 8: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 9: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 8 steps 1: LiOH*H2O / tetrahydrofuran / 0.5 h 2: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1h, 2) THF, 0 deg C, 1 h 3: 47.3 mg / 2-chloro-1-methylpyridinium iodide, NET3 / CH2Cl2 / 6 h / Heating 4: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 5: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 6: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 7: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 8: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 13 steps 1: 71 percent / TBAF / tetrahydrofuran / 2 h 2: NaHCO3, KBr, 4-methoxy-2,2,6,6-tetramethylpiperidinyloxy free radical, NaOCl / CH2Cl2 / 1.33 h / 0 °C 3: NaH2PO4, NaClO2 / 2-methyl-propan-2-ol; H2O; various solvent(s) / 2 h 4: 495 mg / diethyl ether 5: Dess-Martin periodinane / CH2Cl2 / 1 h 6: LiOH*H2O / tetrahydrofuran / 0.5 h 7: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1h, 2) THF, 0 deg C, 1 h 8: 47.3 mg / 2-chloro-1-methylpyridinium iodide, NET3 / CH2Cl2 / 6 h / Heating 9: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 10: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 11: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 12: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 13: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme | |
Multi-step reaction with 11 steps 1: 71 percent / TBAF / tetrahydrofuran / 2 h 2: NaHCO3, KBr, 4-methoxy-2,2,6,6-tetramethylpiperidinyloxy free radical, NaOCl / CH2Cl2 / 1.33 h / 0 °C 3: NaH2PO4, NaClO2 / 2-methyl-propan-2-ol; H2O; various solvent(s) / 2 h 4: 1) TESOTf, 2,6-lutidine, 2) TBAF, AcOH / 1) CH2Cl2, 0 deg C, 1 h, 2) THF, 0 deg C, 1 h 5: 1) 2-chloro-1-methylpyridinium iodide, NEt3, 2) NEt3 / 1) CH2Cl2, reflux, 17 h, 2) EtOH, 5 h 6: 81 percent / Dess-Martin periodinane / CH2Cl2 / 3 h / Ambient temperature 7: 84 percent / L-Selectride / tetrahydrofuran / 0.5 h / -78 °C 8: 83 percent / I2, PPh3, imidazole / toluene / 0.5 h / 75 °C 9: 74 percent / 1) KHMDS / tetrahydrofuran; toluene / 1) -78 deg C, 30 min, 2) 30 min 10: 67 percent / graphite, potassium, ZnCl2, AgOAc / tetrahydrofuran / 1.5 h / Ambient temperature 11: 1) dimethyldioxirane, 2) 40percent HF / 1) acetone, CH2Cl2, -45 deg C -> -25 deg C, 1 h; -25 deg C -> 0 deg C, 1 h, 2) MeCN, 6 h View Scheme |
(9RS,22S)-14-<(tert-butyldimethylsilyl)oxy>-9,22-tetrahydro-24,32-bis<(triisopropylsilyl)oxy>-FK506
Tacrolimus
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1: 82 percent / Dess-Martin periodinane / CH2Cl2 / 15 h / Ambient temperature 2: 73 percent / aq. HF / acetonitrile / 18 h / Ambient temperature View Scheme |
Tacrolimus
Conditions | Yield |
---|---|
With polymer resin accoring to the invention In methanol; acetone`; water Purification / work up; |
triisopropylsilyl trifluoromethanesulfonate
Tacrolimus
C62H109NO12Si2
Conditions | Yield |
---|---|
With 2,6-dimethylpyridine In dichloromethane 1) 0 deg C, 1,5 h, 2) 25 deg C, 16 h; | 99% |
Conditions | Yield |
---|---|
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In 1,2-dichloro-benzene at 150℃; for 0.0833333h; olefin cross-metathesis reaction; Microwave irradiation; Inert atmosphere; | 99% |
Conditions | Yield |
---|---|
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In 1,2-dichloro-benzene at 150℃; for 0.0833333h; olefin cross-metathesis reaction; Microwave irradiation; Inert atmosphere; | 99% |
With Hoveyda-Grubbs catalyst second generation In 1,2-dichloro-ethane at 85℃; for 1h; Inert atmosphere; Sealed tube; Microwave irradiation; | 96% |
With Hoveyda-Grubbs catalyst second generation In 1,2-dichloro-ethane at 85℃; for 1h; Inert atmosphere; Sealed tube; | 96% |
Tacrolimus
D,L-dithiothreitol
Conditions | Yield |
---|---|
With 2,2-dimethoxy-2-phenylacetophenone In dichloromethane for 0.25h; UV-irradiation; | 99% |
Conditions | Yield |
---|---|
With 2,2-dimethoxy-2-phenylacetophenone In dichloromethane at 20℃; for 0.25h; Solvent; Reagent/catalyst; UV-irradiation; | 98% |
With 2,2-dimethoxy-2-phenylacetophenone In dichloromethane at 23℃; for 0.25h; Inert atmosphere; Irradiation; | 96% |
With 2,2-dimethoxy-2-phenylacetophenone In dichloromethane at 23℃; for 0.25h; UV-irradiation; Inert atmosphere; | 96% |
Conditions | Yield |
---|---|
With 2,2-dimethoxy-2-phenylacetophenone In dichloromethane for 0.25h; Reagent/catalyst; UV-irradiation; | 98% |
Conditions | Yield |
---|---|
With zinc(II) chloride for 3h; Ambient temperature; | 97% |
for 3h; Heating; | 82% |
Conditions | Yield |
---|---|
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In 1,2-dichloro-benzene at 150℃; for 0.0833333h; olefin cross-metathesis reaction; Microwave irradiation; Inert atmosphere; | 97% |
Tacrolimus
tert-butyldimethylsilyl chloride
24,33-Bis-(t.butyl-dimethylsilyl)-FK 506
Conditions | Yield |
---|---|
With 1H-imidazole In N,N-dimethyl-formamide | 96.7% |
With 1H-imidazole In N,N-dimethyl-formamide Ambient temperature; |
Conditions | Yield |
---|---|
With 2,2-dimethoxy-2-phenylacetophenone In methanol for 0.25h; UV-irradiation; | 96% |
Conditions | Yield |
---|---|
With Hoveyda-Grubbs catalyst second generation In 1,2-dichloro-ethane at 85℃; for 1h; Inert atmosphere; Microwave irradiation; | 96% |
t-butyldimethylsiyl triflate
Tacrolimus
24,33-Bis-(t.butyl-dimethylsilyl)-FK 506
Conditions | Yield |
---|---|
With 2,6-dimethylpyridine In dichloromethane at 0℃; for 1h; Inert atmosphere; | 95% |
Conditions | Yield |
---|---|
With 2,2-dimethoxy-2-phenylacetophenone In dichloromethane for 0.25h; UV-irradiation; | 95% |
Conditions | Yield |
---|---|
With 2,2-dimethoxy-2-phenylacetophenone In methanol; water for 0.25h; UV-irradiation; | 95% |
With 2,2-dimethoxy-2-phenylacetophenone In methanol; water at 23℃; for 0.25h; Inert atmosphere; UV-irradiation; | 92% |
Conditions | Yield |
---|---|
With Novozym SP435 In toluene at 45℃; for 80h; Inert atmosphere; Schlenk technique; | 95% |
Tacrolimus
22(S)-dihydro-FK-506
Conditions | Yield |
---|---|
With L-Selectride In tetrahydrofuran at -78℃; for 1.5h; | 90% |
With tetramethylammonium triacetoxyborohydride In acetic acid; acetonitrile at -5 - 0℃; for 5h; | 25% |
Multi-step reaction with 3 steps 1: imidazole / dimethylformamide 2: 66 percent / tetramethylammonium triacetoxyborohydride / acetonitrile; acetic acid / 5 h / -5 - 0 °C 3: 87 percent / 40percent aq. HF / acetonitrile / 2 h / 10 °C View Scheme |
Conditions | Yield |
---|---|
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In isopropyl alcohol at 150℃; for 0.0833333h; olefin cross-metathesis reaction; Microwave irradiation; Inert atmosphere; | 88% |
Conditions | Yield |
---|---|
palladium diacetate In dichloromethane Ambient temperature; | 87% |
Conditions | Yield |
---|---|
With palladium diacetate; potassium carbonate; triethylamine; tris-(o-tolyl)phosphine In N,N-dimethyl-formamide at 100℃; for 20h; Inert atmosphere; Schlenk technique; | 82% |
With palladium diacetate; triethylamine; tris-(o-tolyl)phosphine In N,N-dimethyl-formamide at 100℃; for 20h; Heck Reaction; Inert atmosphere; Schlenk technique; | 62% |
Conditions | Yield |
---|---|
With lead(IV) acetate | 81% |
diazomethane
Tacrolimus
(E)-(1R,9S,12S,13R,14S,17R,21S,23S,24R,25S,27R)-17-Allyl-12-[(E)-2-((1R,3R,4R)-3,4-dimethoxy-cyclohexyl)-1-methyl-vinyl]-1-hydroxy-14,23,25-trimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone
Conditions | Yield |
---|---|
With boron trifluoride diethyl etherate In dichloromethane at 0 - 5℃; | 80% |
Tacrolimus
Conditions | Yield |
---|---|
With zinc(II) chloride In dichloromethane for 15h; Ambient temperature; | 80% |
Conditions | Yield |
---|---|
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In 1,2-dichloro-benzene at 150℃; for 0.0833333h; olefin cross-metathesis reaction; Microwave irradiation; Inert atmosphere; | 79% |
Conditions | Yield |
---|---|
With tricyclohexylphosphine[1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidine][benzylidene]ruthenium(II) dichloride In 1,2-dichloro-benzene at 150℃; for 0.0833333h; olefin cross-metathesis reaction; Microwave irradiation; Inert atmosphere; | 79% |
Conditions | Yield |
---|---|
With palladium diacetate; triethylamine; tris-(o-tolyl)phosphine In N,N-dimethyl-formamide at 100℃; for 24h; Heck Reaction; Inert atmosphere; Schlenk technique; | 78% |
Conditions | Yield |
---|---|
With potassium cyanide; 18-crown-6 ether In benzene at 23℃; for 20h; | 76% |
Tacrolimus
Conditions | Yield |
---|---|
With tetra-n-butylammonium cyanide In tetrahydrofuran; water at 5℃; for 2h; | 76% |
Tacrolimus (CAS NO.104987-11-3) was among the first macrolide immunosuppressants discovered, which was discovered in 1984 by a Japanese team headed by T. Goto, T. Kino and H. Hatanaka. The name tacrolimus is derived from 'Tsukuba macrolide immunosuppressant'. Tacrolimus is owned by Astellas Pharma Inc., and is sold under the tradenames Prograf, Advagraf, and Protopic. It was first approved by the Food and Drug Administration (FDA) in 1994 use in liver transplantation, trachea, skin, cornea, and limb transplants.
Organism | Test Type | Route | Reported Dose (Normalized Dose) | Effect | Source |
---|---|---|---|---|---|
mouse | LD50 | intraperitoneal | > 200mg/kg (200mg/kg) | Journal of Antibiotics. Vol. 40, Pg. 1249, 1987. |
The Tacrolimus, with the CAS registry number 104987-11-3,is also known as Tsukubaenolide. It belongs to the product categories of Pharmaceuticals; API;Chiral Reagents.Its EINECS number is 242-042-4. This chemical's molecular formula is C44H69NO12 and molecular weight is 804.02. What's more,Its systematic name is 15,19-Epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone.It is a White Crystalline Solid which is used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection. In recent years, it has been used to suppress the inflammation associated with ulcerative colitis. It is a recent addition in the treatment of eczema, particularly atopic dermatitis, and suppresses inflammation in a similar way to steroids.
Physical properties about Tacrolimus are:
(1)ACD/LogP: 3.96; (2)# of Rule of 5 Violations: 2; (3)ACD/LogD (pH 5.5): 3.96; (4)ACD/LogD (pH 7.4): 3.96; (5)ACD/BCF (pH 5.5): 602.10; (6)ACD/BCF (pH 7.4): 600.47; (7)ACD/KOC (pH 5.5): 3398.48; (8)ACD/KOC (pH 7.4): 3389.29; (9)#H bond acceptors: 13; (10)#H bond donors: 3; (11)#Freely Rotating Bonds: 10; (12)Index of Refraction: 1.549; (13)Molar Refractivity: 214.131 cm3; (14)Molar Volume: 673.124 cm3; (15)Surface Tension: 51.2929992675781 dyne/cm; (16)Density: 1.194 g/cm3; (17)Flash Point: 481 °C; (18)Enthalpy of Vaporization: 143.946 kJ/mol; (19)Boiling Point: 871.721 °C at 760 mmHg; (20)Vapour Pressure: 0 mmHg at 25°C.
You can still convert the following datas into molecular structure:
(1)SMILES:O=C3C(=O)N1CCCC[C@H]1C(=O)O[C@H](C(=C/[C@@H]2CC[C@@H](O)[C@H](OC)C2)/C)[C@H](C)[C@@H](O)CC(=O)[C@@H](/C=C(\C[C@@H](C[C@H](OC)[C@H]4O[C@]3(O)[C@H](C)C[C@@H]4OC)C)C)C\C=C;
(2)Std. InChI:InChI=1S/C44H69NO12/c1-10-13-31-19-25(2)18-26(3)20-37(54-8)40-38(55-9)22-28(5)44(52,57-40)41(49)42(50)45-17-12-11-14-32(45)43(51)56-39(29(6)34(47)24-35(31)48)27(4)21-30-15-16-33(46)36(23-30)53-7/h10,19,21,26,28-34,36-40,46-47,52H,1,11-18,20,22-24H2,2-9H3/b25-19+,27-21+/t26-,28+,29+,30-,31+,32-,33+,34-,36+,37-,38-,39+,40+,44+/m0/s1;
(3)Std. InChIKey:QJJXYPPXXYFBGM-LFZNUXCKSA-N.
The toxicity data of Tacrolimus are as follows:
Organism | Test Type | Route | Reported Dose (Normalized Dose) | Effect | Source |
---|---|---|---|---|---|
mouse | LD50 | intraperitoneal | > 200mg/kg (200mg/kg) | Journal of Antibiotics. Vol. 40, Pg. 1249, 1987. |
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