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[ CAS No. 162648-54-6 ] {[proInfo.proName]}

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Chemical Structure| 162648-54-6
Chemical Structure| 162648-54-6
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Product Details of [ 162648-54-6 ]

CAS No. :162648-54-6 MDL No. :MFCD00273464
Formula : C22H23NO4 Boiling Point : -
Linear Structure Formula :- InChI Key :VCIVAWBKUQJNSX-UHFFFAOYSA-N
M.W :365.42 Pubchem ID :2756093
Synonyms :

Safety of [ 162648-54-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 162648-54-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 162648-54-6 ]

[ 162648-54-6 ] Synthesis Path-Downstream   1~33

  • 1
  • [ 147762-53-6 ]
  • [ 188751-44-2 ]
  • [ 162648-54-6 ]
  • [(S)-1-[1-((1R,6S)-6-Carbamoyl-cyclohex-2-enylcarbamoyl)-cyclohexylcarbamoyl]-2-(4-phosphonooxy-phenyl)-ethyl]-carbamic acid 3-amino-benzyl ester [ No CAS ]
  • [(S)-1-[1-((1S,6R)-6-Carbamoyl-cyclohex-2-enylcarbamoyl)-cyclohexylcarbamoyl]-2-(4-phosphonooxy-phenyl)-ethyl]-carbamic acid 3-amino-benzyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-<(dimethylamino)-1H-1,2,3-triazolo<4,5-b>pyridin-1-ylmethylene>-N-methylmethanaminium hexaflurophosphate N-oxide; O-(1,2-dihydro-2-oxo-1-pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine Multistep reaction;
  • 2
  • [ 24781-50-8 ]
  • [ 127633-36-7 ]
  • [ 144120-53-6 ]
  • [ 162648-54-6 ]
  • Ac2O [ No CAS ]
  • Phosphoric acid mono-[4-((S)-2-acetylamino-2-{1-[(S)-2-carbamoyl-1-(3-naphthalen-1-yl-propylcarbamoyl)-ethylcarbamoyl]-cyclohexylcarbamoyl}-ethyl)-phenyl] ester [ No CAS ]
  • 3
  • [ 147762-53-6 ]
  • [ 188751-44-2 ]
  • [ 162648-54-6 ]
  • [(S)-1-[1-((1R,6S)-6-Carbamoyl-cyclohex-2-enylcarbamoyl)-cyclohexylcarbamoyl]-2-(4-phosphonooxy-phenyl)-ethyl]-carbamic acid 3-amino-benzyl ester [ No CAS ]
  • [(S)-1-[1-((1S,6R)-6-Carbamoyl-cyclohex-2-enylcarbamoyl)-cyclohexylcarbamoyl]-2-(4-phosphonooxy-phenyl)-ethyl]-carbamic acid 3-amino-benzyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multistep reaction;
  • 4
  • [ 71989-20-3 ]
  • [ 94744-50-0 ]
  • [ 139551-83-0 ]
  • [ 162648-54-6 ]
  • Fmoc-Ala [ No CAS ]
  • Fmoc-Leu [ No CAS ]
  • Ac-Trp-Ala-Aib-Ac6c-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leu-ol [ No CAS ]
  • 5
  • [ 313709-63-6 ]
  • [ 64362-32-9 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • {3-[(S)-5-[(3-Benzoyl-pyridine-2-carbonyl)-amino]-5-(1-carbamoyl-cyclohexylcarbamoyl)-pentylcarbamoyl]-phenoxy}-acetic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multistep reaction;
  • 6
  • [ 6314-28-9 ]
  • [ 35661-40-6 ]
  • [ 102-83-0 ]
  • [ 162648-54-6 ]
  • C36H50N4O3S [ No CAS ]
  • 7
  • [ 6314-28-9 ]
  • [ 86123-10-6 ]
  • [ 102-83-0 ]
  • [ 162648-54-6 ]
  • C36H50N4O3S [ No CAS ]
  • 8
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 2-(4-(1H-benzoimidazol-2-ylamino)phenyl)acetic acid [ No CAS ]
  • C42H51N9O7 [ No CAS ]
  • 9
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 2-(4-(1H-benzoimidazol-2-ylamino)phenyl)propanoic acid [ No CAS ]
  • C43H53N9O7 [ No CAS ]
  • 10
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 2-(4-(4-methyl-1H-benzoimidazol-2-ylamino)phenyl)acetic acid [ No CAS ]
  • C43H53N9O7 [ No CAS ]
  • 11
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 2-(4-(5-bromo-1H-benzoimidazol-2-ylamino)phenyl)acetic acid [ No CAS ]
  • C42H50BrN9O7 [ No CAS ]
  • 12
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 2-(o-tolylamino)-1H-benzoimidazole-5-carboxylic acid [ No CAS ]
  • C42H51N9O7 [ No CAS ]
  • 13
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 3-(1H-benzoimidazol-2-ylamino)benzoic acid [ No CAS ]
  • C41H49N9O7 [ No CAS ]
  • 14
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 3-(4-(1H-benzoimidazol-2-ylamino)phenyl)propanoic acid [ No CAS ]
  • C43H53N9O7 [ No CAS ]
  • 15
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 4-(1H-benzoimidazol-2-ylamino)benzoic acid [ No CAS ]
  • C41H49N9O7 [ No CAS ]
  • 16
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • 4-(4-methyl-1H-benzoimidazol-2-ylamino)benzoic acid [ No CAS ]
  • C42H51N9O7 [ No CAS ]
  • 17
  • [ 13094-51-4 ]
  • C38H33N2O4PolS [ No CAS ]
  • [ 68858-20-8 ]
  • [ 191348-16-0 ]
  • [ 71989-16-7 ]
  • [ 162648-54-6 ]
  • [ 1163708-03-9 ]
  • 18
  • [ 13094-51-4 ]
  • C38H33N2O4PolS [ No CAS ]
  • [ 112883-29-1 ]
  • [ 191348-16-0 ]
  • [ 71989-16-7 ]
  • [ 162648-54-6 ]
  • [ 1163708-04-0 ]
  • 19
  • [ 13094-51-4 ]
  • C38H33N2O4PolS [ No CAS ]
  • [ 35737-15-6 ]
  • [ 191348-16-0 ]
  • [ 71989-16-7 ]
  • [ 162648-54-6 ]
  • [ 1163708-05-1 ]
  • 20
  • [ 13094-51-4 ]
  • C38H33N2O4PolS [ No CAS ]
  • [ 191348-16-0 ]
  • [ 71989-16-7 ]
  • N-(9-fluorenylmethoxycarbonyl)-3-(β-naphthyl)-L-alanine [ No CAS ]
  • [ 162648-54-6 ]
  • [ 1163708-06-2 ]
  • 21
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 162648-54-6 ]
  • C31H47N6O6Pol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Rink amide resin (2.35 g, 1.19 mmol) was swollen in DMF (30 mL) for 3 h, followed by treatment with 20% piperidine in DMF (20 mL). After washing, the resin was then treated with a pre-mixed solution of Fmoc-Ach-OH (Fmoc-Ach-OH; 1.30 g, 3.57 mmol), 1,3- diisopropylcarbodiimide (DIC; 3.57 mmol, 553 muL), and hydroxybenzotriazole (HOBt; 482 mg, 3.57 mmol) in DMF (20 mL) followed by shaking for 6 h. After a negative Kaiser test'21' washing, this sequence of deprotection/coupling was repeated thrice more with Fmoc- Aad(rBu)-OH (Fmoc-Aad(riBu)-OH; 1.57 g, 3.57 mmol), Dde-K(Fmoc)-OH (Dde-K(Fmoc)- OH; 1.85 g, 3.57 mmol), and (E)-3-(pyridin-3-yl)acrylic acid (532 mg, 3.57 mmol). After washing, the Dde-tripeptide resin was washed and treated with 2% H2NNH2 in DMF (20 mL) for 20 min, followed by washing to afford the free amino-tripeptide resin 1 : IR (neat) 3430 (sh), 3370 (sh), 3084, 1740 (st), 1684 (st), 1680 (st), 1662 (st), 1654 (st) cm"1.
  • 22
  • [ 159751-47-0 ]
  • [ 19337-97-4 ]
  • [ 146982-27-6 ]
  • N-(tert-butoxycarbonyl)-S-trityl-D-cysteine [ No CAS ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • [ 181517-99-7 ]
  • [ 613245-91-3 ]
  • [ 1426413-17-3 ]
YieldReaction ConditionsOperation in experiment
Rink amide MBHA resin (0.5 g, 0.325 mmol, loading 0.65 mmol/g) was swollen in DMF for 3 hours before Fmoc-deprotection with 20% 4-methylpiperidine in DMF twice (5 and 15 minutes, respectively). The beads were then washed with DMF (3x10 mL), methanol (MeOH) (3x10 mL) and DMF (3x10 mL), respectively. Fmoc-Lys(Dde)-OH ( 0.519 g, 0.975 mmol) was dissolved in a solution of N-Hydroxybenzotriazole (HOBt) (0.149 g, 0.975 mmol) and N,N'-diisopropylcarbidiimide (DIC) (152 uL, 0.975 mmol) in DMF (8 mL), which was then added to the suspension of the beads. The coupling was carried out at room temperature overnight. After filtration, the beads were washed with DMF (3x10 mL), MeOH (3x10 mL), and DMF (3x10 mL), respectively. After removal of Fmoc, the beads were then subjected to two cycles of coupling with and deprotection of the Fmoc-linker in the same manner as described above. The beads were washed with DMF (3x10 mL), MeOH (3x10 mL) and DMF (3x10 mL). Fmoc-Ach-OH (0.365 g, 0.975 mmol) was dissolved in a solution of HOBt (0.149 g, 0.975 mmol) and DIC (152 uL, 0.975 mmol) in DMF, and was then added into the beads. The coupling was carried out at room temperature for 2 hours. After filtration, the beads were washed with DMF (3x10 mL), MeOH (3x10 mL), and DMF (3x10 mL), respectively. The Fmoc deprotection group was removed with 20% 4-methylpiperidine twice ((5 and 15 minutes, respectively)). After washing with DMF, MeOH, and DMF respectively, the beads were then subjected to additional coupling and deprotection cycles stepwise with Fmoc-Aad(OtBu)-OH and Fmoc-Lys(Alloc)-OH in the same manner as described above. After removal of Fmoc, a solution of UPA (0.923 g, 3.25 mmol), HOBt (0.498 g, 3.25 mmol) and DIC (509 mu,, 3.25 mmol) in DMF was added to the beads. The reaction was conducted at room temperature until Kaiser test negative (3 hours to overnight). The beads were washed with DMF (3x10 mL), methanol (3x 10 mL), and DMF (3x10 mL). The Alloc protecting group was removed by treating with Pd(PPh3)4 (0.2 eq.) and PhSiH3 (20eq.) in dichloromethane (DCM), twice (30 minutes, each). A solution of trans-3-(3-pyridyl)acrylic acid (0.37 g, 1.3 mmol), HOBt (0.176 g, 1.3 mmol) and DIC (201 mu, 1 .3 mmol) in DMF (8 mL) was added to the beads. The coupling proceeded at room temperature 4 hours to overnight until Kaiser test was negative. The beads were washed with DMF (5 x 5 mL), MeOH (3 x 5 mL) and DCM (3 x 5 mL). The Dde protecting group was removed with 2% NH2NH2 in DMF twice (5 and 10 minutes, respectively). The beads were washed with DMF, MeOH and DMF, followed by coupling of (4 eq. to resin, 220 mg, 1.3 mmol) Boc-D-Cys(Trt)-OH, HOBt (0.176 g, 1.3 mmol) and DIC (201 iL, 1.3 mmol) in DMF (8 mL). The coupling reaction was conducted at room temperature until Kaiser test negative (4 hours to overnight). The beads were thoroughly washed with DMF, MeOH and DCM, respectively, and then dried under vacuum for 1 hour before adding a cleavage mixture of 82.5% trifluoroacetic acid (TFA): 5% thioanisole: 5% phenol:5% water: 2.5% triisopropylsilane (TIS) (v/v). The cleavage reaction was conducted at room temperature over 2-3 hours. The off-white crude product was precipitated out and washed with cold ether. The purity was determined by analytical reverse phase high performance liquid chromatography (RP-HPLC) and the crude product was used in the next step without further purification. LLP2A-Lys(D-Cys) MALDI-TOF MS [M+H]+: 1502.88 (calculated: 1502.77); [M+Na]+: 1524.88 (calculated: 1524.75).
  • 23
  • [ 36321-43-4 ]
  • [ 162648-54-6 ]
  • [ 1453814-87-3 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; diisopropyl-carbodiimide In tetrahydrofuran at 20℃; for 18h; General procedure: To a 100 mL round-bottomed flask add equimolar 2a and 2b, 1.2 equiv 1-hydroxybenzotriazole (HOBt), 1.2 equiv DIC, 2.5 equiv N,N-diisopropylethylamine (DIEA), the mixture was stirred in about 30mL dry THF at room temperature for 18h. The solvents were removed in vacuo to give white solid 3a, without further purification, 3a was subjected to 16mL DMF and 4mL piperidine for 30min. The product was added 100 mL deionized water, and extracted twince with 20mL CH2Cl2, dried over anhydrous sodium sulfate. The solvents were removed in vacuo, flash chromatography of the residue on silica gel (CH2Cl2/CH3OH=8:1, v/v) gave pure product 4a. Compounds 4b-4g were prepared with the same procedure.
  • 24
  • [ 21746-40-7 ]
  • N(α)-Fmoc-N(δ)-trityl-L-glutamine 4-benzyloxybenzyl ester Wang resin-bound [ No CAS ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • Fmoc-Tyr(tBu)-Ser(ψMe,MePro)-OH [ No CAS ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-23-6 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 71989-28-1 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 109425-51-6 ]
  • [ 143824-78-6 ]
  • [ 162648-54-6 ]
  • (Ac-1-amino-1-cyclohexanecarboxylic acid) SerAspTyrSerIleAlaMetAspLysIleHisGlnGlnAspPheValAsnTrpLeuLeuAlaGlnLysGlyLysLysAsnAspTrpLysHisAsnCys(propylsuccinimide)ThrGln-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
1% Stage #1: N(α)-Fmoc-N(δ)-trityl-L-glutamine 4-benzyloxybenzyl ester Wang resin-bound With piperidine; benzotriazol-1-ol In N,N-dimethyl-formamide at 75℃; for 0.0583333h; Microwave irradiation; Inert atmosphere; Stage #2: Fmoc-Thr(tBu)-OH With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide at 75℃; for 0.0833333h; Microwave irradiation; Inert atmosphere; Stage #3: propylmaleimide; N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-Val-OH; Fmoc-Leu-OH; N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine; Fmoc-Tyr(tBu)-Ser(ψMe,MePro)-OH; N-Fmoc L-Phe; Fmoc-Ser(tBu)-OH; Fmoc-(tBu)Asp-OH; Fmoc-Ile-OH; Fmoc-Lys(tert-butoxycarbonyl); N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine; N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-methionine; L-Asn(Trt); Fmoc-L-Gln(Trt)-OH; Fmoc-His(Trt)-OH; 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester; 1-[((9H-fluoren-9-yl)methoxy)carbonylamino]cyclohexanecarboxylic acid Further stages; 2 Example 2: [Ac-A6c7, Cys(Psu)40]hGIP(7-42)-OH Example 2: [Ac-A6c7, Cys(Psu)40]hGIP(7-42)-OH Solid-phase peptide synthesis was used to assemble the peptide using microwave-assisted Fmoc Chemistry on a Liberty Peptide Synthesizer (CEM; Matthews, NC, USA) at the 0.1 mmole scale. Pre-loaded Fmoc-Gln(Trt)-Wang resin (0.59 mmole/g; Novabiochem, San Diego, CA, USA) was used to generate the C-terminal acid peptide. The resin (0.17 g) was placed in a 50 ml conical tube along with 15 ml of dimethylformamide (DMF) and loaded onto a resin position on the synthesizer. The resin was then quantitatively transferred to the reaction vessel via the automated process. The standard Liberty synthesis protocol for 0.1 mmole scale synthesis was used. This protocol involves deprotecting the N-terminal Fmoc moiety via an initial treatment with 7 ml of 20% piperidine, containing 0.1M N-hydroxybenzotriazole (HOBT), in DMF. The initial deprotection step was for 30 seconds with microwave power (45 watts, maximum temperature of 75 °C), and nitrogen bubbling (3 seconds on / 7 seconds off). The reaction vessel was then drained and a second piperidine treatment, identical to the first treatment, except that it was for a 3-minute duration. The resin was then drained and thoroughly washed with DMF several times. The protected amino acid, Fmoc-Thr(tBu)-OH, prepared as 0.2M stock solution in DMF, was then added (2.5 ml, 5 equivalents), followed by 1.0 ml of 0.45M (4.5 eq.) HBTU [2-(1H-benzo-triazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosaphate] in DMF. This was followed by the addition of 0.5 ml of 2M (10 eq.) DIPEA (diisopropylethylamine) in NMP (N-methylpyrrollidinone). The coupling step was performed for 5 minutes using 20 watts of microwave power, a max temperature of 75 °C, and the same rate of nitrogen bubbling. Following the initial coupling step, the reaction vessel was drained to waste and the coupling step repeated. Cycle 2 was then initiated similar to cycle 1. All amino acids were introduced similarly and a double-coupling strategy was employed throughout the entire sequence. Cycles 1-3, 19-20, 25-26, and 30-34 contained a capping procedure immediately following the coupling step. Capping was performed by adding 7 ml of 0.5M acetic anhydride, containing 0.015M HOBT in NMP, along with 2 ml of the 2M DIPEA solution using a multi-step microwave protocol: 50 watts of power for 30 seconds (65 °C max temperature), followed by 30 seconds of microwave power off, followed by a second round of 30 seconds of microwave power on (50 watts), and then again 30 seconds of no microwave power. The resin was then drained and thoroughly washed with DMF. The following amino acids (Advanced Chemtech; Louisville, KY, USA) were used: Cycle 1: Fmoc-Thr(OtBu)-OH; Cycle 2: Fmoc-Cys(Trt)-OH; Cycle 3: Fmoc-Asn(Trt)-OH; Cycle 4: Fmoc-His(Trt)-OH; Cycle 5: Fmoc-Lys(Boc)-OH; Cycle 6: Fmoc-Trp(Boc)-OH; Cycle 7: Fmoc-Asp(OtBu)-OH; Cycle 8: Fmoc-Asn(Trt)-OH; Cycle 9: Fmoc-Lys(Boc)-OH; Cycle 10: Fmoc-Lys(Boc)-OH; Cycle 11: Fmoc-Gly-OH; Cycle 12: Fmoc-Lys(Boc)-OH; Cycle 13: Fmoc-Gln(Trt)-OH; Cycle 14: Fmoc-Ala-OH; Cycle 15: Fmoc-Leu-OH; Cycle 16: Fmoc-Leu-OH; Cycle 17: Fmoc-Trp(Boc)-OH; Cycle 18: Fmoc-Asn(Trt)-OH; Cycle 19: Fmoc-Val-OH; Cycle 20: Fmoc-Phe-OH; Cycle 21: Fmoc-Asp(OtBu)-OH; Cycle 22: Fmoc-Gln(Trt)-OH; Cycle 23: Fmoc-Gln(Trt)-OH; Cycle 24: Fmoc-His(Trt)-OH; Cycle 25: Fmoc-Ile-OH; Cycle 26: Fmoc-Lys(Boc)-OH; Cycle 27: Fmoc-Asp(OtBu)-OH; Cycle 28: Fmoc-Met-OH; Cycle 29: Fmoc-Ala-OH; Cycle 30: Fmoc-Ile-OH; Cycle 31: Fmoc-Tyr(tBu)-Ser(psiMe,Me,Pro)-OH; Cycle 32: Fmoc-Asp(OtBu)-OH; Cycle 33: Fmoc-Ser(tBu)-OH; and Cycle 34: Fmoc-A6c-OH. Once the peptide backbone was complete, the resin was treated with piperidine solution to remove the N-terminal Fmoc group, followed by treatment with the standard capping procedure in order to acetylate the N-terminus. The resin was then thoroughly washed with DMF and then transferred back to the 50 ml conical tube using DMF as the transfer solvent. The resin was deprotected and cleaved from the resin via treatment with 5 ml of the following reagent; 5% TIS, 2% water, 5% (w/v) dithiothrieitol (DTT), 88% TFA, and allowed to mix for 3.5 hours. The filtrate was collected into 45 ml of cold anhydrous ethyl ether. The precipitate was pelleted for 10 minutes at 3500 RPM in a refrigerated centrifuge. The ether was decanted, and the peptide re-suspended in fresh ether. The ether workup was performed a total of 2 times. Following the last ether wash the peptide was allowed to air dry to remove residual ether. The peptide pellet was resuspended in 8 ml of acetonitrile (Acn) followed by 8ml of de-ionized water, and allowed to fully dissolve. The peptide solution was then analyzed by mass spectrometry. Mass analysis employing electrospray ionization identified a main product containing a mass of 4358.0 Daltons; corresponding to the acetylated,linear product. The crude product (approximately 500 mg) was analysed by HPLC, employing a 250 x 4.6 mm C18 column (Phenomenex; Torrance, CA, USA) using a gradient of 2-80% acetonitrile (0.1% TFA) over 30 minutes. Analytical HPLC identified a product with 38% purity. The crude peptide was then purified on a preparative HPLC equipped with a C18 reverse phase column using a 10-60% acetonirile (0.1% TFA) over 50 minutes at a 10 ml/min flowrate. The purified peptide was then lyophilized yielding 15 mg of peptide. The linear peptide was then derivatized with N-propylmaleimide (Pma) to generate the propylsuccinimide (Psu) derivative on the Cysteine side chain. The purified linear peptide was brought up in water, adjusted to pH 6.5 with ammonium carbonate, at 5mg/ml. Five equivalents of Pma was added with constant stirring for 30 seconds. The derivatized peptide solution was then analyzed by mass spectrometry. Mass analysis identified a main product containing a mass of 4498.6 Daltons; corresponding to the desired Psu derivatized product. The product was then re-purified via preparative HPLC using a similar gradient as before. The purified product was analyzed by HPLC for purity (95.2%) and mass spectrometry (4498.6 Daltons) and subsequently lyophilized. Following lyophillization, 4.3 mg of purified product was obtained representing a 1% yield.
  • 25
  • (S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetic acid [ No CAS ]
  • [ 101555-63-9 ]
  • [ 162648-54-6 ]
  • (S)-N-(1-carbamoylcyclohexyl)-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl)piperidine-2-carboxamide [ No CAS ]
  • 26
  • [ 35661-39-3 ]
  • [ 112883-29-1 ]
  • [ 35661-40-6 ]
  • [ 104091-09-0 ]
  • [ 35737-15-6 ]
  • [ 71989-20-3 ]
  • [ 71989-31-6 ]
  • [ 162648-54-6 ]
  • Phe-Phe-Gln-Tyr-Ala-Trp-Glu-Tyr-D-Proline-Chx [ No CAS ]
YieldReaction ConditionsOperation in experiment
Examples 1 to 42 and 44 to 54 shown in Table 1. (0669) The peptides were synthesized according the general method starting with the amino acid L-Ala which was grafted to the resin (Fmoc-Ala-2-chlorotrityl resin). The linear peptides were synthesized on the solid support according to the procedure described above in the following sequence: Res -Ate-P4-?3-?2-?1-2-1-?8-?7-?6. The products were cleaved from the resin, cyclized, deprotected and purified by preparative reverse phase LC-MS as described above. After lyophilisation the products were obtained as white to off-white powders and characterised by HPLC-MS, analytical method A, B, or C as described above. For analytical data, see Ex. 1 to 42 and 44 to 54 in Table 1. 1.1 General synthetic procedures (0634) A general method for the synthesis of the peptidomimetics of the present invention is exemplified in the following. This is to demonstrate the principal concept and does not limit or restrict the present invention in any way. A person skilled in the art is easily able to modify these procedures, especially, but not limited to, choosing a different starting position within the ring system, to still achieve the preparation of the claimed cyclic peptidomimetic compounds of the present invention. (0635) Coupling of the first protected amino acid residue to the resin (0636) In a dried flask, 2-chlorotritylchloride resin (polystyrene, 1% crosslinked; loading: 1.4 mmol/g) was swollen in dry CH2CI2 for 30 min (7 ml CH2CI2 per g resin). A solution of 0.8 eq of the Fmoc-protected amino acid and 6 eq of DIPEA in dry CH2CI2/DMF (4/1, v/v) (10 ml per g resin) was added. After shaking for 2-4 h at rt the resin was filtered off and washed successively with CH2CI2, DMF, CH2CI2, DMF and CH2CI2. Then a solution of dry CH2CI2/MeOH/DIPEA (17:2:1, v/v/v) was added (10 ml per g resin). After shaking for 3 x 30 min the resin was filtered off in a pre-weighed sinter funnel and washed successively with CH2CI2, DMF, CH2CI2, MeOH, CH2CI2, MeOH, CH2CI2 (2x) and Et20 (2x). The resin was dried under high vacuum overnight. The final mass of resin was calculated before the qualitative control. (0637) The following preloaded resins were prepared: Fmoc-Ala-2-chlorotrityl resin and Fmoc- Leu-2-chlorotrityl resin. (0638) Synthesis of the fully protected peptide fragment (0639) The synthesis was carried out on a Syro-peptide synthesizer (MultiSynTech GmbH) using 24 to 96 reaction vessels. In each vessel were placed approximately 80 mg of the above resin (weight of the resin before loading). The following reaction cycles were programmed and carried out: (0640) Step Reagent Time (0641) 1 CH2CI2, wash and swell (manual) 1 x 3 min (0642) 2 DM F, wash and swell 2 x 30 min (0643) 3 20 % piperidine/DMF 1 x 5 min and 1 x 15 min (0644) 4 DM F, wash 5 x 1 min (0645) 5 3.5 eq. Fmoc amino acid/3.5 eq. HOAt in DM F or NM P (0646) + 3.5 eq. PyBOP/7 eq DI PEA or 3.5 eq. DIC 1 x 40 min (0647) 6 3.5 eq. Fmoc amino acid/3.5 eq. HOAt in DM F or NM P (0648) + 3.5 eq. HATU or PyBOP or HCTU (0649) + 7 eq. DI PEA 1 x 40 min (0650) 7 DM F, wash 5 x 1 min (0651) 8 20 % piperidine/DMF 1 x 5 min and 1 x 15 min (0652) 9 DM F, wash 5 x 1 min (0653) 10 CH2CI2, wash (at the end of the synthesis) 3 x 1 min (0654) Steps 5 to 9 are repeated to add each amino-acid residue. (0655) After the synthesis of the fully protected peptide fragment had been terminated, the cleavage, cyclization and work up procedures, as described herein below, were used for the preparation of the final compounds. (0656) Cleavage, backbone cyclization and deprotection of the peptide (0657) After assembly of the linear peptide, the resin was suspended in 1 ml of 1% TFA in CH2CI2 (v/v; 0.14 mmol) for 3 minutes and filtered, and the filtrate was neutralized with 1 ml of 20% DI PEA in CH2CI2 (v/v; 1.15 mmol). This procedure was repeated four times to ensure completion of the cleavage. The resin was washed three times with 1 ml of CH2CI2. The CH2CI2 layers containing product were evaporated to dryness. The fully protected linear peptide was solubilised in 8 ml of dry DM F. Then 2 eq. of HATU and 2. eq. of HOAt in dry DMF (1-2 ml) and 4 eq. of DIPEA in dry DM F (1-2 ml) were added to the peptide, followed by stirring for ca . 16 h. The volatiles were removed by evaporation. The crude cyclic peptide was dissolved in 7 ml of CH2CI2 and washed three times with 4.5 ml 10% acetonitrile in water (v/v). The CH2CI2 layer was then evaporated to dryness. (0658) To fully deprotect the peptide, 4-7 ml of cleavage cocktail TFA/TIS/H20 (95:2.5:2.5, v/v/v) was added, and the mixture was kept for 2.5-4 h at room temperature until the reaction was completed. The reaction mixture was evaporated close to dryness and the peptide precipitated with 7 mL of cold Et20/pentane (1:1, v/v). The precipitate was washed three times with 3 mL of cold Et20/pentane (1:1, v/v), and was subsequently purified by preparative reverse phase LC-MS. After lyophilisation the products were obtained t...
  • 27
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 35661-40-6 ]
  • [ 104091-09-0 ]
  • [ 35737-15-6 ]
  • [ 71989-31-6 ]
  • [ 162648-54-6 ]
  • C66H89N11O13 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 43 is shown in Table 1. (0670) The peptide was synthesized according to the general method starting with the amino acid L-Leu which was grafted to the resin (Fmoc-Leu-2-chlorotrityl resin). The linear peptide was synthesized on the solid support according to the procedure described above in the following sequence: Resin-Leu-P^P^P^T^T1-?8-?7-?6-?5. The product was cleaved from the resin, cyclized, deprotected and purified by preparative reverse phase LC-MS as described above. (0671) After lyophilisation the product was obtained as white to off-white powder and characterised by HPLC-MS, analytical method B as described above. For analytical data, see Ex. 43 in Table 1. 1.1 General synthetic procedures (0634) A general method for the synthesis of the peptidomimetics of the present invention is exemplified in the following. This is to demonstrate the principal concept and does not limit or restrict the present invention in any way. A person skilled in the art is easily able to modify these procedures, especially, but not limited to, choosing a different starting position within the ring system, to still achieve the preparation of the claimed cyclic peptidomimetic compounds of the present invention. (0635) Coupling of the first protected amino acid residue to the resin (0636) In a dried flask, 2-chlorotritylchloride resin (polystyrene, 1% crosslinked; loading: 1.4 mmol/g) was swollen in dry CH2CI2 for 30 min (7 ml CH2CI2 per g resin). A solution of 0.8 eq of the Fmoc-protected amino acid and 6 eq of DIPEA in dry CH2CI2/DMF (4/1, v/v) (10 ml per g resin) was added. After shaking for 2-4 h at rt the resin was filtered off and washed successively with CH2CI2, DMF, CH2CI2, DMF and CH2CI2. Then a solution of dry CH2CI2/MeOH/DIPEA (17:2:1, v/v/v) was added (10 ml per g resin). After shaking for 3 x 30 min the resin was filtered off in a pre-weighed sinter funnel and washed successively with CH2CI2, DMF, CH2CI2, MeOH, CH2CI2, MeOH, CH2CI2 (2x) and Et20 (2x). The resin was dried under high vacuum overnight. The final mass of resin was calculated before the qualitative control. (0637) The following preloaded resins were prepared: Fmoc-Ala-2-chlorotrityl resin and Fmoc- Leu-2-chlorotrityl resin. (0638) Synthesis of the fully protected peptide fragment (0639) The synthesis was carried out on a Syro-peptide synthesizer (MultiSynTech GmbH) using 24 to 96 reaction vessels. In each vessel were placed approximately 80 mg of the above resin (weight of the resin before loading). The following reaction cycles were programmed and carried out: (0640) Step Reagent Time (0641) 1 CH2CI2, wash and swell (manual) 1 x 3 min (0642) 2 DM F, wash and swell 2 x 30 min (0643) 3 20 % piperidine/DMF 1 x 5 min and 1 x 15 min (0644) 4 DM F, wash 5 x 1 min (0645) 5 3.5 eq. Fmoc amino acid/3.5 eq. HOAt in DM F or NM P (0646) + 3.5 eq. PyBOP/7 eq DI PEA or 3.5 eq. DIC 1 x 40 min (0647) 6 3.5 eq. Fmoc amino acid/3.5 eq. HOAt in DM F or NM P (0648) + 3.5 eq. HATU or PyBOP or HCTU (0649) + 7 eq. DI PEA 1 x 40 min (0650) 7 DM F, wash 5 x 1 min (0651) 8 20 % piperidine/DMF 1 x 5 min and 1 x 15 min (0652) 9 DM F, wash 5 x 1 min (0653) 10 CH2CI2, wash (at the end of the synthesis) 3 x 1 min (0654) Steps 5 to 9 are repeated to add each amino-acid residue. (0655) After the synthesis of the fully protected peptide fragment had been terminated, the cleavage, cyclization and work up procedures, as described herein below, were used for the preparation of the final compounds. (0656) Cleavage, backbone cyclization and deprotection of the peptide (0657) After assembly of the linear peptide, the resin was suspended in 1 ml of 1% TFA in CH2CI2 (v/v; 0.14 mmol) for 3 minutes and filtered, and the filtrate was neutralized with 1 ml of 20% DI PEA in CH2CI2 (v/v; 1.15 mmol). This procedure was repeated four times to ensure completion of the cleavage. The resin was washed three times with 1 ml of CH2CI2. The CH2CI2 layers containing product were evaporated to dryness. The fully protected linear peptide was solubilised in 8 ml of dry DM F. Then 2 eq. of HATU and 2. eq. of HOAt in dry DMF (1-2 ml) and 4 eq. of DIPEA in dry DM F (1-2 ml) were added to the peptide, followed by stirring for ca . 16 h. The volatiles were removed by evaporation. The crude cyclic peptide was dissolved in 7 ml of CH2CI2 and washed three times with 4.5 ml 10% acetonitrile in water (v/v). The CH2CI2 layer was then evaporated to dryness. (0658) To fully deprotect the peptide, 4-7 ml of cleavage cocktail TFA/TIS/H20 (95:2.5:2.5, v/v/v) was added, and the mixture was kept for 2.5-4 h at room temperature until the reaction was completed. The reaction mixture was evaporated close to dryness and the peptide precipitated with 7 mL of cold Et20/pentane (1:1, v/v). The precipitate was washed three times with 3 mL of cold Et20/pentane (1:1, v/v), and was subsequently purified by preparative reverse phase LC-MS. After lyophilisation the products were obtained typically as white to off-white powders and ...
  • 28
  • [ 159751-47-0 ]
  • O-bis-(aminoethyl)ethylene glycol trityl resin [ No CAS ]
  • [ 19337-97-4 ]
  • Fmoc-Lys(Dde)-OH [ No CAS ]
  • [ 162648-54-6 ]
  • [ 181517-99-7 ]
  • H<SUB>2</SUB>N-PEG<SUB>2</SUB>-LLP2A(O<SUP>t</SUP>Bu) [ No CAS ]
  • 29
  • [ 86123-10-6 ]
  • [ 109425-51-6 ]
  • [ 146982-24-3 ]
  • [ 143824-78-6 ]
  • [ 162648-54-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [Ac6c-His-D-Phe-Arg-Trp-Asp]-amide [ No CAS ]
  • 30
  • [ 109425-51-6 ]
  • [ 146982-24-3 ]
  • [ 143824-78-6 ]
  • N-[(9-fluorenyl)methoxycarbonyl]-3-(2-naphthyl)-D-alanine [ No CAS ]
  • [ 162648-54-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [Ac6c-His-DNal(2’)-Arg-Trp-Asp]-amide [ No CAS ]
  • 31
  • Fmoc-gly-wang resin [ No CAS ]
  • [ 35661-60-0 ]
  • [ 35661-40-6 ]
  • [ 108-24-7 ]
  • [ 118358-38-6 ]
  • [ 162648-54-6 ]
  • Fmoc-Arg(*)-OH [ No CAS ]
  • Ac-RCyRRCyRRCyRS*FLRCyRCyRCyRG, S*= L-serine glycosylated with D-glucose, Cy= 1-(amino)cyclohexanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Peptides were synthesized on a 100 μηιοΙ scale using a CEM Liberty microwave Peptide Synthesizer (Buckingham, UK) and Fmoc chemistry following manufacturer's recommendations. The side chain protecting groups used were labile to trifluoroacetic acid treatment and the peptide was synthesized using a 5-fold excess of Fmoc-protected amino acids (0.25 mmol) that were activated using PyBOP (5-fold excess) in the presence of DIPEA or with DIC|Oxyma. Piperidine (20% v/v in DMF) was used to remove N-Fmoc protecting groups. The coupling was carried out once at 75 C for 5 min at 60-watt microwave power except for arginine and the glycosylated amino acid residues, which were coupled twice each. (0452) Histidine and cysteine residues were coupled once at 50C for 5 min at 60-watt microwave power. Each deprotection reaction was carried out at 75 C twice, once for 30 sec and then for 3 min at 35-watt microwave power. Once synthesis was complete, the resin was washed with DMF (3 x 50 mL) and the N-terminus of the solid phase bound peptide was acetylated with acetic anhydride in the presence of DIPEA. The peptide was cleaved from the solid support by treatment with a cleavage cocktail consisting of trifluoroacetic acid (TFA): 3,6- dioxa-1 ,8-octanedithiol (DODT): H20: triisopropylsilane (TIPS) (94%: 2.5%: 2.5%: 1 %, 10 mL) or trifluoroacetic acid (TFA): H20: m-cresol: triisopropylsilane (TIPS) (94%: 2.5%: 2.5%: 1 %, (0453) 1 mL) or trifluoroacetic acid (TFA): H20: triisopropylsilane (TIPS) (96.5%: 2.5%: 1 %, 1 mL) for (0454) 2 h at room temperature for 2-3 h at room temperature. Excess TFA was removed by blowing N2 through the peptide solution. The cleaved peptide was precipitated via the addition of ice- cold diethyl ether and centrifuged at 3000 rpm for 5 min. The peptide pellet was washed in ice-cold diethyl ether thrice. The crude peptide was dissolved in water, analyzed and purified by RP-HPLC on Phenomenex Jupiter column (21.2 X 250 mm, C18, 10 μηι) at a flow rate of 20 mL/min with the following gradient (A: 0.1 % TFA, B: 90% CH3CN, 0.1 % TFA) 0-2 min 5% B 2-35 min 5%-60% B 35-40 min 60%-90% B used. The fractions containing the desired peptide were combined and lyophilized to give the product as a white solid.
  • 32
  • [ 159751-47-0 ]
  • [ 21947-98-8 ]
  • C29H31N3O5 [ No CAS ]
  • [ 150629-67-7 ]
  • [ 162648-54-6 ]
  • [ 181517-99-7 ]
  • [ 613245-91-3 ]
  • C72H109N15O18S [ No CAS ]
YieldReaction ConditionsOperation in experiment
The synthetic approach used to synthesize YLL8-Lys(D-Cys) is shown below in Scheme 2. Rink amide MBHA resin (0.5 g, 0.325 mmol, loading 0.65 mmol/g) was swollen in DMF for 3 hours. Fmoc was deprotected with 20% 4-methylpiperidine in DMF twice (5 and 15 minutes, respectively). After filtration, the beads were then washed with DMF (3x10 mL), methanol (MeOH) (3x10 mL) and DMF (3x10 mL), respectively. Fmoc-Lys(Dde)-OH (0.519 g, 0.975 mmol) was dissolved in a solution of 6-C1 HOBt (0.165 g, 0.975 mmol) and DIC (152 pL, 0.975 mmol) in DMF (8 mL), which was then added to the suspension of the beads. The coupling was carried out at room temperature overnight. After filtration, the beads were washed with DMF (3x10 mL), MeOH (3x10 mL), and DMF (3x10 mL), respectively. Fmoc was deprotected with 20% 4-methylpiperidine in DMF (8 mL) twice (5 and 15 minutes, respectively). Fmoc-Linker (0.612 g, 1.3 mmol) was dissolved in a solution of HOBt (0.22 g, 1.3 mmol) and DIC (201 pL, 1.3 mmol) in DMF (8 mL), which was then added to the suspension of the beads. The coupling was carried out at room temperature until Kaiser test is negative. After filtration, the beads were washed with DMF (3x10 mL), MeOH (3x10 mL), and DMF (3x10 mL), respectively. Fmoc was deprotected with 20% 4-methylpiperidine in DMF (8 mL) twice (5 and 15 minutes, respectively). Fmoc-Linker (0.612 g, 1.3 mmol) was dissolved in a solution of HOBt (0.22 g, 1.3 mmol) and DIC (201 pL, 1.3 mmol) in DMF (8 mL), which was then added to the suspension of the beads. The coupling was carried out at room temperature until Kaiser test is negative. After filtration, the beads were washed with DMF (3x10 mL), MeOH (3x10 mL), and DMF (3x10 mL), respectively. Fmoc was deprotected with 20% 4-methylpiperidine in DMF (8 mL) twice (5 and 15 minutes, respectively). After filtration, the beads were washed with DMF (3x10 mL), MeOH (3x10 mL), and DMF (3x10 mL), respectively. Fmoc-Ach-OH (0.365 g, 0.975 mmol) was dissolved in a solution of 6-C1 HOBt (0.165 g, 0.975 mmol) and DIC (152 pL, 0.975 mmol) in DMF, and was then added to the beads. The coupling was carried out at room temperature for 2 hours.After filtration, the beads were washed with DMF (3x10 mL), MeOH (3x10 mL), and DMF (3x10 mL), respectively. The Fmoc deprotection group was removed with 20% 4- methylpiperidine twice (5 and 15 minutes, respectively). After washing with DMF, MeOH, and DMF respectively, the beads were then subjected to additional coupling and deprotection cycles stepwise with Fmoc-Aad(0/Bu)-OH, Fmoc-Lys(Al2) and UPA in the same manner as described above.The Dde protecting group was removed with 2% hydrazine monohydrate in DMF twice (5 and 10 minutes, respectively) and the beads were again washed with DMF, MeOH and DMF, followed by coupling of Boc-D-Cys(Trt)-OH (4 eq. to resin, 220 mg, 1.3 mmol), HOBt (0T76g, 1.3 mmol), and DIC (201 pL, 1.3 mmol) in DMF (8 mL). The coupling reaction was conducted at room temperature until Kaiser test negative (4 hours to overnight). The beads were thoroughly washed with DMF, MeOH and DCM, respectively, and then dried under vacuum for 1 hour before adding a cleavage mixture (8 mL) of 82.5%trifluoroacetic acid (TFA): 5% thioanisole: 5% phenol:5% water: 2.5% triisopropylsilane (TIS) (v/v). The cleavage reaction was conducted at room temperature over 2-3 hours. The off-white crude product was precipitated out and washed with cold diethyl ether. The purity was determined by analytical HPLC and the crude product was used in the next step without further purification.
  • 33
  • [ 159751-47-0 ]
  • C29H31N3O5 [ No CAS ]
  • [ 162648-54-6 ]
  • [ 181517-99-7 ]
  • C43H56N8O8 [ No CAS ]
YieldReaction ConditionsOperation in experiment
YLL8 was synthesized on Rink amide MBHA resin (GL Biochem, Shanghai,China) using standard solid phase peptide synthesis method. In brief, Rink amide MBHA resin (0.5 g, 0.325 mmol, loading 0.65 mmol/g) was swollen in DMF for 2 h before Fmoc- deprotection with 20% 4-methylpiperidine in DMF twice (5 min, 15 min). The beads were washed with DMF (3x10 mL), MeOH (3x10 mL) and DMF (3x10 mL). Fmoc-Ach-OH (0.365 g, 0.975 mmol) was dissolved in a solution of 6-C1 HOBt (0.165 g, 0.975 mmol) and DIC (152 pL, 0.975 mmol) in DMF, and was then added into the beads. The coupling was carried out at room temperature for 2 h. After filtration, the beads were washed with DMF (3x10 mL), MeOH (3x10 mL), and DMF (3x10 mL), respectively, three times each. The Fmoc deprotection group was removed with 20% 4-methylpiperidine twice (5 min, 15 min). After washing with DMF, MeOH, and DMF respectively, the beads were then subjected to additional coupling and deprotection cycles stepwise with Fmoc-Aad(tBu) and Fmoc-Lys(Al2) in the same manner as described above. After removal of Fmoc, a solution of 4-[(N?-2-methylphenyl)ureido]phenylacetic acid(UPA, 0.923 g, 3.25 mmol), HOBt (0.498 g, 3.25 mmol) and DIC (509 pL, 3.25 mmol) in DMF was added to the beads. The reaction was conducted at room temperature overnight. The beads were washed with DMF (5 x 5 mL), MeOH (3 x 5 mL) and DCM (3 x 5 mL). The beads were then dried in vacuo for 1 h before adding a cleavage mixture of 95% TFA: 2.5% water: 2.5% TIS. The cleavage reaction was conducted at room temperature for 2 h. The liquid was collected and concentrated. The crude product was precipitated with diethyl ether and purified using preparative RP-HPLC. The fraction was collected and lyophilized to give designed product YLL8, MALDI-TOF MS: 813.30 daltons.
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