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Chemical Structure| 84793-07-7 Chemical Structure| 84793-07-7
Chemical Structure| 84793-07-7

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Fmoc-Glu-OtBu is a glutamic acid derivative, commonly used in peptide synthesis and drug development.

Synonyms: N-(9-Fluorenylmethoxycarbonyl)glutamic acid α-tert-butyl ester

4.5 *For Research Use Only !

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Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

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Product Details of Fmoc-Glu-OtBu

CAS No. :84793-07-7
Formula : C24H27NO6
M.W : 425.47
SMILES Code : C(C)(C)(C)OC([C@@H](NC(=O)OCC2C1=CC=CC=C1C3=CC=CC=C23)CCC(=O)O)=O
Synonyms :
N-(9-Fluorenylmethoxycarbonyl)glutamic acid α-tert-butyl ester
MDL No. :MFCD00065648
InChI Key :GOPWHXPXSPIIQZ-FQEVSTJZSA-N
Pubchem ID :7017912

Safety of Fmoc-Glu-OtBu

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of Fmoc-Glu-OtBu

* 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 [ 84793-07-7 ]

[ 84793-07-7 ] Synthesis Path-Downstream   1~27

  • 1
  • [ 84793-07-7 ]
  • [ 104091-08-9 ]
  • [ 1562-93-2 ]
  • N-[4-phenylazobenzoyl]-D-α-glutamyl-glutamic acid [ No CAS ]
  • 3
  • [ 84793-07-7 ]
  • [ 104091-08-9 ]
  • [ 88574-06-5 ]
  • [ 188715-40-4 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • C46H74N10O20 [ No CAS ]
YieldReaction ConditionsOperation in experiment
PSMA-i was synthesized manually using standard Fmoc chemistry. Generally, peptide was synthesized at 0.2 mmol scale starting from C-terminal Fmoc-rink amide MBHA resin. Fmoc-deprotection at each cycle was carried out using 20% pipperidine in DMF. Coupling reactions were caffied out using 3.3 equiv of Fmoc-amino acids in DMF activated with 3.3 equiv of HCTU and 5 equiv of diisopropylethylamine (DIPEA) in DMF. These steps were repeated each time with an amino acid added. After the peptide sequence Fmoc-Glu?-Amc-Ahx-Glu-Glu-Glu-Lys(Mtt) was built on the resin, the Fmoc group of Nterminal amino acid Glu? was deprotected by 20% pipperidine. Then, a chloroform solution containing 3 eq of H-Glu(OtBu)-OtBu mixed with 2.5eq of DIPEA were prepared. The solution is then added slowly to 0.25 eq triphosgene in chloroform over 10 minutes at room temperature. After 15 minute incubation to allow for isocyanate formation, the reaction mixture was mixed with Glu?-Amc-Ahx-Glu-Glu-Glu-Lys on rink amide resin pre-swollen in chloroform with 2.5 eq of DIPEA. After the reaction was complete, the resin was washed with DMF and then dichloromethane and dried. The peptide was cleaved from resin by TFA/water/triisopropylsilane (950:25:25). The cleaved peptide was purified by preparative HPLC. The products were ascertained by high resolution matrix-assisted laser desorption/ionization mass (MALDI-MS) spectra from an Applied Biosystem 4800 MALDI TOF/TOF Analyzer in positive ion mode. Retention time: 19.0 mm. MALDI MS:C48H74N10020, 1087.5 (found); 1087.1 (calculated).
  • 4
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • 3-(9-carboxy-nonyloxy)benzoic acid tert-butyl ester [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{4-carboxy-4-[10-(3-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{4-carboxy-4-[10-(3-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS Method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OH was used in position 26, and Boc-His(trt)-OH was used in position 7. The Mtt was removedwith HFIP, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech),Fmoc-Glu-OtBu, and 3-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester were coupled using a double couplingmethod on the Liberty Peptide synthesiser.UPLC (method 04_A4_1): 10.01 minUPLC (method 08_B4_1): 8.81 minLCMS4: m/z = 978.5 (M+5H)5+, 1222.8 (M+4H)4+, 1630.1 (M+3H)3+
  • 5
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-[2-(2-{2-[10-(4-carboxyphenoxy)decanoylamino]ethoxy}ethoxy)acetyl])-EFIAWLVRGRK(Nε-[2-(2-{2-[10-(4-carboxyphenoxy)decanoylamino]ethoxy}ethoxy)acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling.Preparation method: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin.Fmoc-Lys(Mtt)-OH was used in position 26, and Boc-His(trt)-OH was used in position 7. The Mtt was removed withHFIP, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech)and 4-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester (prepared as described in Example 25, step 2 of WO2006/082204) were coupled using a double coupling method on the Liberty Peptide synthesiserUPLC (method 04_A3_1): 10.51 minLCMS4: m/z = 1085.2 (M+4H)4+, 1447.3 (M+3H)3+
  • 6
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε{2-[2-(2-{2-[2-(2-{(S)-4-Carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acet yl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OHwas used in position 26, and Boc-His(Trt)-OH was used in position 7. The Mtt was removed with HFIP, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech), Fmoc-Glu-OtBu,and 4-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester (prepared as described in Example 25, step 2 of WO2006/082204) were coupled using a double coupling method on the Liberty Peptide synthesiser.UPLC (method 04_A3_1): 7.19 minLCMS4: m/z = 978.5 (M+5H)5+, 1222.8 (M+4H)4+ 1630.1 (M+3H)3+
  • 7
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OHwas used in position 26, and Boc-His(Trt)-OH was used in position 7. The Mtt was removed with HFIP, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech), Fmoc-Glu-OtBuand 4-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester (prepared as described in Example 25, step 2 of WO2006/082204) were coupled using SPPS method D.UPLC (method 08_B4_1): Rt = 8.8 minUPLC (method 04_A3_1): Rt = 9.6 minLCMS4: 4598.0Calculated MW = 4598.2
  • 8
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-EFIAWLVRGRK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS method BLCMS4: Rt = 2.12 min, m/z: 4916.0UPLC (method: 08_B2_1): Rt = 12.59 minUPLC (method: 04_A3_1): Rt = 10.57 min
  • 9
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-GGTFTSDVSSYLEGQAAK(Nε-[2-[2-[2-[[2-[2-[2-[[(2S)-4-carboxy-2-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-EFIAWLVRGRK(Nε-[2-[2-[2-[[2-[2-[2-[[(2S)-4-carboxy-2-[10-(4-carboxyphenoxy)decanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SSPS method BUPLC (method:08_B2_1): Rt = 13.193 minUPLC (method:05_B5_1): Rt = 6.685 minLCMS4: m/z: 4887; m/3:1630; m/4:1222; m/5:978
  • 10
  • [ 905303-12-0 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-((S)-4-carboxy-4-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}butyryl))-EFIAWLVRGRK(Nε-((S)-4-carboxy-4-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}butyryl))-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OH was usedin position 26, and Boc-His(Trt)-OH was used in position 7. The Mtt was removed with HFIP, and Fmoc-Glu-OtBu and4-(9-carboxy-nonyloxy)-benzoic acid tert-butyl ester (prepared as described in Example 25, step 2 of WO 2006/082204)were coupled using SPPS method D.UPLC (method 08_B4_1): Rt = 8.6 minUPLC (method 04_A3_1): Rt = 7.9 minLCMS4: 4565.0Calculated MW = 4566.1
  • 11
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 27913-58-2 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[4-(4-iodophenyl)butyrylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[4-(4-iodophenyl)butyrylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual couplingPreparation method: SPPS method B, 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commerciallyavailable from Iris Biotech), <strong>[27913-58-2]4-(4-iodophenyl)butyric acid</strong> (commercially available from Aldrich) and Fmoc-Glu-OtBu were coupled using SPPS method D.UPLC (method 04_A4_1): Rt = 8.54 minUPLC (method 01_A4_2): Rt = 10.23 minLCMS4: Rt = 2.4 min, m/z = 971 (m/5) 1213 (m/44) 1617 (m/3)
  • 12
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • 3-(11-carboxy-undecyloxy)benzoic acid tert-butyl ester [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[12-(3-carboxyphenoxy)dodecanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[12-(3-carboxyphenoxy)dodecanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS Method B. The 3-(11-carboxy-undecyloxy)-benzoic acid tert-butyl ester was preparedin similar fashion as described for 3-(15-carboxy-pentadecyloxy)-benzoic acid tert-butyl ester, empoying 12-bromododecanoicacid. The final product was characterised by analytical UPLC and LC-MS with the exception that an aceticanhydride capping step was performed after the coupling of the following amino acids: Trp31, Ala25, Tyr19, Phe12 andAib8 (2© min, 65°C with 1 N Acetic acid anhydride in NMP)UPLC (method 08_B4_1): Rt = 9.449 minLCMS4: Rt = 2.37 min, m/z = m/z: 1011.88(m/4); 1264.32(m/3); 4942.24Calculated MW = 4944.608
  • 13
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 4521-22-6 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[4-(4-methylphenyl)butyrylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[4-(4-methylphenyl)butyrylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commerciallyavailable from Iris Biotech), <strong>[4521-22-6]4-(4-methylphenyl)butyric acid</strong> (commercially available from ABCR) and Fmoc-Glu-OtBuwere coupled using SPPS method D.UPLC (method 01_B4_1): Rt = 9.93 minLCMS4: Rt = 2.44 min, m/z = 926(m/5) 1157(m/4) 1543(m/3)
  • 14
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 234082-00-9 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{(S)-4-carboxy-4-[2-(2-{2-[(13-carboxytridecanoylamino)]ethoxy}ethoxy)acetylamino]butyrylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{(S)-4-carboxy-4-[2-(2-{2-[(13-carboxytridecanoylamino)]ethoxy}ethoxy)acetylamino]butyrylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OH was usedin position 26, and Boc-His(trt)-OH was used in position 7. The Mtt was removed with HFIP manually, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech), Fmoc-Glu-OtBu andtetradecanedioc were coupled using a double coupling method on the Liberty Peptide synthesiser. The theoreticalmolecular mass was confirmed by MALDI-MS.UPLC (method 08_B4_1): Rt = 8.6 minUPLC (method 04_A3_1): Rt = 9.7 minMALDI-MS: 4788
  • 15
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 234082-00-9 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-[(S)-4-carboxy-4-{2-[2-(2-[2-(2-{2-[(13-carboxytridecanoylamino)]ethoxy}ethoxy)acetylamino]ethoxy)ethoxy] acetylamino}butyryl])-EFIAWLVRGRK(Nε-[(S)-4-carboxy-4-{2-[2-(2-[2-(2-{2-[(13-carboxytridecanoylamino)]ethoxy}ethoxy)acetylamino]ethoxy)ethoxy]acetylamino}butyryl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, starting with low-load Fmoc-Lys(Mtt)-Wang resin. Fmoc-Lys(Mtt)-OH was used in position 26, and Boc-His(trt)-OH was used in position 7. The Mtt was removed with HFIP manually, and 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commercially available from Iris Biotech), Fmoc-Glu-OtBu andtetradecanedioc were coupled using a double coupling method on the Liberty Peptide synthesiser. The theoreticalmolecular mass was confirmed by MALDI-MS.UPLC (method 08_B4_1): Rt = 8.8 minUPLC (method 04_A3_1): Rt = 10 minMALDI-MS: 4787
  • 16
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • 4-(7-carboxyheptyloxy)benzoic acid tert-butyl ester [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[8-(4-carboxyphenoxy)octanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-EFIAWLVRGRK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[8-(4-carboxyphenoxy)octanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS method BLCMS4: Rt: 1.93 min, m/z: 4832.4; M/4: 1208.5; M/3: 1611.0UPLC (method 09_B4_1): Rt = 8.10 minUPLC (method 04_A3_1): Rt = 8.15 minUPLC (method 05_B5_1): Rt = 5.30 min
  • 17
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • 5-(12-carboxydodecyl)thiophene-2-carboxylic acid tertbutyl ester [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[13-(5-carboxythiophene-2-yl)tridecanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-EFIAWLVRGRK(Nε-[2-[2-[2-[[2-[2-[2-[[(4S)-4-carboxy-4-[13-(5-carboxythiophene-2-yl)tridecanoylamino]butanoyl]amino]ethoxy]ethoxy]acetyl]amino]ethoxy]ethoxy]acetyl])-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preperation method: SSPS method B. 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commerciallyavailable from Iris Biotech), Fmoc-Glu-OtBu, and 5-(12-Carboxy-dodecyl)-thiophene-2-carboxylic acid tertbutylester (prepared as described in Example 6 of WO07128815) were coupled using SSPS method D method on theLiberty synthesiser.UPLC (method 08_B4_1): Rt = 9.87 minLCMS4: m/z =1651 (m/3), 1239 (m/4), 991 (m/5)
  • 18
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • C27H44O5 [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[16-(4-carboxyphenoxy)hexadecanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[16-(4-carboxyphenoxy)hexadecanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation method: SPPS Method B. The final product was characterised by analytical UPLC and LC-MS withthe exception that an acetic anhydride capping step was performed after the coupling of the following amino acids:Trp31, Ala25, Tyr19, Phe12 and Aib8 (2© min, 65°C with 1 N Acetic acid anhydride in NMP). The 4-(15-carboxypentadecyloxy)benzoic acid tert-butyl ester can be prepared as decribed in Example 17 in WO07128817.UPLC (method 08_B4_1): Rt = 11.272 minUPLC (method 05_B10_1): Rt = 7.319 minLCMS4: Rt = 2.37 min, m/z = 5054.48 Calculated MW = 5056.82
  • 19
  • [ 24475-36-3 ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • C41H39N2O3Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 62-57-7 ]
  • [ 32926-43-5 ]
  • [ 166108-71-0 ]
  • Fmoc-Arg(pg)-OH [ No CAS ]
  • Fmoc-Trp(pg)-OH [ No CAS ]
  • Fmoc-Gln(pg)-OH [ No CAS ]
  • Fmoc-Tyr(pg)-OH [ No CAS ]
  • Fmoc-Ser(pg)-OH [ No CAS ]
  • Fmoc-Asp(pg)-OH [ No CAS ]
  • Fmoc-Thr(pg)-OH [ No CAS ]
  • H-Aib-EGTFTSDVSSYLEGQAAK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-[4-(4-tert-butylphenyl)butyrylamino]-4-carboxybutyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-EFIAWLVRGRK(Nε-{2-[2-(2-{2-[2-(2-{(S)-4-[4-(4-tert-butylphenyl)butyrylamino]-4-carboxybutyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl})-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
SPPS method B refers to the synthesis of a protected peptidyl resin using Fmoc chemistry on a microwave based Liberty peptide synthesiser (CEM Corp., North Carolina). A suitable resin is a pre-loaded, low-load Wang resinavailable from Novabiochem (e.g. low load Fmoc-Lys(Mtt)-Wang resin, 0.35 mmol/g). Fmoc-deprotection was with 5percentpiperidine in NMP at up to 70 or 75°C. The coupling chemistry was DIC/HOAt in NMP. Amino acid/HOAt solutions (0.3M in NMP at a molar excess of 3-10 fold) were added to the resin followed by the same molar equivalent of DIC (0.75Min NMP). For example, the following amounts of 0.3M amino acid/HOAt solution were used per coupling for the followingscale reactions: Scale/ml, 0.10 mmol/2.5 ml, 0.25 mmol/5 ml, 1 mmol/15 ml. Coupling times and temperatures weregenerally 5 minutes at up to 70 or 75°C. Longer coupling times were used for larger scale reactions, for example 10min. Histidine amino acids were double coupled at 50°C, or quadruple coupled if the previous amino acid was stericallyhindered (e.g. Aib). Arginine amino acids were coupled at RT for 25 min then heated to 70 or 75°C for 5 min. Someamino acids such as but not limited to Aib, were "double coupled", meaning that after the first coupling (e.g. 5 min at75°C), the resin is drained and more reagents are added (amino acid, HOAt and DIC), and the mixture in heated again(e.g. 5 min at 75°C). When a chemical modification of a lysine side chain was desired, the lysine was incorporated asLys(Mtt). The Mtt group was removed by washing the resin with DCM and suspending the resin in neat (undiluted)hexafluoroisopropanol for 20 minutes followed by washing with DCM and NMP. The chemical modification of the lysinewas performed either by manual synthesis (see SPPS method D) or by one or more automated steps on the Libertypeptide synthesiser as described above, using suitably protected building blocks (see General methods), optionallyincluding a manual coupling. Preparation: SPPS method B, 8-(9-fluorenylmethyloxycarbonyl-amino)-3,6-dioxaoctanoic acid (commerciallyavailable from Iris Biotech), 4-(4-t-butylphenyl)butyric acid and Fmoc-Glu-OtBu were coupled using SPPS method D.UPLC (method 08_B4_1): Rt = 9.07 minLCMS4: Rt = 2.29 min, m/z = 943 (m/5) 1179 (m/4) 1571 (m/3)
  • 20
  • [ 404858-60-2 ]
  • [ 64987-85-5 ]
  • [ 29022-11-5 ]
  • [ 112883-29-1 ]
  • [ 84793-07-7 ]
  • [ 180839-17-2 ]
  • E′E-Amc-Ahx-dEdEdEGYGGGC-NH2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Fmoc-?E-Amc-Ahx-dGlu-dGlu-dGlu-Gly-Tyr-Gly-Gly-Gly-Cys-NH2 (SEQ ID NO: 12) was assembled on the resin using standard Fmoc peptide synthesis. Fmoc-?E stands for Fmoc(Glu)-OtBu where the gamma-carboxyl group is unprotected. After removal of the last Fmoc on the assembled peptide, the resin is washed with DMF, methanol and chloroform. Then, a chloroform solution containing a 5-fold excess of H-Glu(OtBu)-OtBu mixed with 2.5 eq (with respect to H-Glu(OtBu)-OtBu) of diisopropylethylamine was prepared. The solution was then added slowly to 0.25 eq (with respect to H-Glu(OtBu)-OtBu) triphosgene over 10 minutes at room temperature. The presumed product of this reaction is an isocyanate derivative of H-Glu(OtBu)-OtBu. After a 15 minute incubation to allow for isocyanate formation, the reaction is mixed with the ?E-Amc-Ahx-Glu-Glu-Glu-Gly-Tyr-Gly-Gly-Gly-Cys-NH2 (SEQ ID NO: 13) on a rink amide resin pre-swollen in chloroform with 2.5 eq of diisopropylethylamine. After 30 minutes of mixing, a Ninhydrin test was administered to test for residual free-amine on the resin. Once the reaction is complete, the resin is washed and the complete peptide product is cleaved. The product elutes at 12.4 minutes on analytical HPLC column with a 10percent-95percent gradient in 40 minutes (flow rate 0.8 ml/min; A: water with 0.1percent TFA; B: acetonitrile). The mass was verified by MALDI/TOF mass spectrometry?Calculated: 1452.6 (C60H88N14O26S). found m/z: 1453.4 (M+1).
  • 21
  • [ 64987-85-5 ]
  • [ 112883-29-1 ]
  • [ 84793-07-7 ]
  • [ 71989-18-9 ]
  • [ 105047-45-8 ]
  • [ 180839-17-2 ]
  • Fmoc-‘E-Amc-Ahx-dGlu-dGlu-dGlu-Tyr-Lys-NH2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
Fmoc-?E-Amc-Ahx-dGlu-dGlu-dGlu-Tyr-Lys-NH2 (SEQ ID NO: 14) was assembled on the resin using standard Fmoc peptide synthesis. The glutamates (dGlu) are D-isomers. Fmoc-?E stands for Fmoc(Glu)-OtBu where the gamma-carboxyl group is unprotected. The last Fmoc on the assembled peptide is then removed by 20percent piperidine. Then a chloroform solution containing 5 eq. of H-Glu(OtBu)-OtBu mixed with 2.5 eq (with respect to H-Glu(OtBu)-OtBu) of diisopropylethylamine was prepared. The solution was then added slowly to 0.25 eq (with respect to H-Glu(OtBu)-OtBu) triphosgene in chloroform over 10 minutes at room temperature. After a 15 minute incubation to allow for isocyanate formation, the reaction is mixed with the ?E-Amc-Ahx-Glu-Glu-Glu-Gly-Tyr-Gly-Gly-Gly-Cys-NH2 (SEQ ID NO: 13) on a rink amide resin pre-swollen in chloroform with 2.5 eq of diisopropylethylamine. After 30 minutes of mixing, a Ninhydrin test was administered to test for residual free-amine on the resin. The reaction was repeated if needed. Once the reaction is complete, the resin is washed and the complete peptide product is cleaved. To couple the purified peptide E?EAmc-Ahx-EEEYK(Bn-NOTA)-NH2 (SEQ ID NO: 15) with SCN-Bn-NOTA (Macrocyclics), E?EAmc-Ahx-dEdEdEYK (SEQ ID NO: 16) was dissolved in DMF at a concentration of 25 mg/mL and an equimolar amount of SCN-Bn-NOTA was dissolved in DMSO at a concentration of 200 mg/mL. After mixing the above DMF and DMSO solutions of the reactants, DIPEA was added to concentration of 2percent v/v. The reaction was monitored by HPLC and allowed to proceed up to 2 hours. Then, glacial acetic acid equivolume to DIPEA is added to stop the reaction. The final product was E?EAmc-Ahx-dGlu-dGlu-dGlu-Tyr-Lys(Bn-NOTA)-NH2 (compound 4) (SEQ ID NO: 8) The product elutes at 14.8 min on an analytical column with a 10percent-90percent gradient in 45 minutes with a flow rate of 0.8 ml/min (A: water with 0.1percent TFA; B: acetonitrile). The mass was verified by MALDI/TOF mass spectrometry?Calculated: 1699.7. found m/z: 1700.7 (M+1).
  • 22
  • [ 84793-07-7 ]
  • [ 188715-40-4 ]
  • [ 234081-98-2 ]
  • [ 166108-71-0 ]
  • C45H80N4O14 [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% 2-Chlorotrityl resin 100-200 mesh 1.8 mmol/g (1, 11.9 g, 21.4 mmol) was left to swell in dry dichloromethane (80 ml) for 20 minutes. A solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 5.50 g, 14.3 mmol) and N,N-diisopropylethylamine (9.44 ml, 54.2 mmol) in dry dichloromethane (70 ml) was added to resin and the mixture was shaken for 4 hours. Resin was filtered and 10 treated with a solution of N,N-diisopropylethylamine (4.97 ml, 28.5 mmol) in methanol/dichloromethane mixture (4: 1, 2 x 5 min, 2 x 57 ml). Then resin was washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,Ndimethylformamide (3 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was 15 washed with N,N-dimethylformamide (3 x 80 ml), 2-propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 11.0 g, 28.5 mmol), 0-( 6-chloro-benzotriazol-1-yi)-N,N,N', N'-tetramethyluronium tetrafluoroborate (TCTU, 10.1 g, 28.5 mmol) and N,N-diisopropylethylamine (9.93 ml, 57.0 mmol) in N,N20 dimethylformamide (80 ml) was added to resin and mixture was shaken for 2 hours. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,N-N,N-dimethylformamide (3 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 225 propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of (S)-2-(9Hfluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 1-tert-butyl ester (Fmoc-LGiu OtBu, 9.11 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.60 g, 21.4 mmol) and N,N-diisopropylethylamine (6.71 ml, 38.5 mmol) in N,N-dimethylformamide (80 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 5 ml), dichloromethane (2 x 80 ml) and N,N-dimethylformamide (2 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of 4-[(9Hfluoren-9-ylmethoxycarbonylamino)methyl]cyclohexanecarboxylic acid (<strong>[188715-40-4]Fmoc-Trx-OH</strong>, 10 9.11 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.60 g, 21.4 mmol) and N,N-diisopropylethylamine (6.71 ml, 38.5 mmol) in N,N-dimethylformamide (80 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,N-dimethylformamide (2 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of dodecanedioic acid mono-tert-butyl ester (C12(0tBu)-OH, 6.13 g, 21.4 mmol), 0-(6chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.61 g, 20 21.4 mmol) and N,N-diisopropylethylamine (6.71 ml, 38.5 mmol) in dichloromethane/N,N-dimethylformamide mixture (4: 1, 80 ml) was added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,Ndimethylformamide (6 x 80 ml), dichloromethane (4 x 80 ml), methanol (4 x 80 ml) and dichloromethane (7 x 80 ml). The product was cleaved from resin by treatment with 25 2,2,2-trifluoroethanol (80 ml) for 18 hours. Resin was filtered off and washed with dichloromethane (4 x 80 ml), dichloromethane/2-propanol mixture (1:1, 4 x 80 ml), 2propanol (2 x 80 ml) and dichloromethane (6 x 80 ml). Solutions were combined; solvent evaporated and crude product was purified by column chromatography (Silicagel 60, 0.040-0-063 mm; eluent: dichloromethane/methanol 1:0-9:1). The pure product (2) 30 was dried in vacuo and obtained as oil. Yield: 5.40 g (42%). RF (Si02, dichloromethane/methanol 9: 1): 0.30. 1H NMR spectrum (300 MHz, CDC13, dH): 7.45-7.31 (m, 1 H); 7.10-6.97 (m, 1 H); 6.716.60 (m, 1 H); 5.70-5.58 (m, 1 H); 4.43-4.31 (m, 1 H); 4.15 (s, 2 H); 4.01 (s, 2 H); 35 3.79-3.31 (m, 16 H); 3.13-3.08 (m, 2 H); 2.28-1.79 (m, 11 H); 1.71-1.51 (m, 4 H); 1.46 (s, 9 H); 1.44 (s, 9 H); 1.25 (bs, 12 H); 1.05-0.88 (m, 2 H).LC-MS purity: 100%. LC-MS Rt (Sunfire 4.6 mm x 100 mm, acetonitrile/water 50:50 to 100:0 + 0.1% FA): 2.16 min. LC-MS m/z: 903.0 (M+H)+.
  • 23
  • [ 843666-27-3 ]
  • [ 84793-07-7 ]
  • [ 188715-40-4 ]
  • [ 166108-71-0 ]
  • C49H88N4O14 [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% 2-Chlorotrityl resin 100-200 mesh 1.8 mmol/g (1, 11.9 g, 21.4 mmol) was left to swell in dry dichloromethane (80 ml) for 20 minutes. A solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 5.50 g, 14.3 mmol) and N,N-diisopropylethylamine (9.44 ml, 54.2 mmol) in dry dichloromethane (70 ml) was added to resin and the mixture was shaken for 4 hours. Resin was filtered and 20 treated with a solution of N,N-diisopropylethylamine (4.97 ml, 28.5 mmol) in methanol/dichloromethane mixture (4: 1, 2 x 5 min, 2 x 57 ml). Then resin was washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,Ndimethylformamide (3 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2-propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 11.0 g, 28.5 mmol), 0-( 6-chloro-benzotriazol-1-yi)-N,N,N', N'-tetramethyluronium tetrafluoroborate 5 (TCTU, 10.1 g, 28.5 mmol) and N,N-diisopropylethylamine (9.93 ml, 57.0 mmol) in N,Ndimethylformamide (80 ml) was added to resin and mixture was shaken for 2 hours. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,N-N,N-dimethylformamide (3 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 10 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of (S)-2-(9Hfluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 1-tert-butyl ester (Fmoc-LGiuOtBu, 9.11 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.60 g, 21.4 mmol) and N,N-diisopropylethylamine (6.71 ml, 15 38.5 mmol) in N,N-dimethylformamide (80 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,N-dimethylformamide (2 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 220 propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of Fmoctranexamic acid (<strong>[188715-40-4]Fmoc-Trx-OH</strong>, 9.11 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 7.60 g, 21.4 mmol) and N,Ndiisopropylethylamine (6.71 ml, 38.5 mmol) in N,N-dimethylformamide (80 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with 25 N,N-dimethylformamide (2 x 80 ml), dichloromethane (2 x 80 ml) and N,Ndimethylformamide (2 x 80 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 30 min, 2 x 80 ml). Resin was washed with N,N-dimethylformamide (3 x 80 ml), 2-propanol (2 x 80 ml) and dichloromethane (100 ml, 2 x 80 ml). Solution of hexadecanedioic acid mono-tert-butyl ester (C16(0tBu)-OH, 7.33 g, 21.4 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'tetramethyluronium tetrafluoroborate (TCTU, 7.61 g, 21.4 mmol) and N,Ndiisopropylethylamine (6.71 ml, 38.5 mmol) in dichloromethane/N,N-dimethylformamide mixture (4: 1, 80 ml) was added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (6 x 80 ml), dichloromethane (4 x 35 80 ml), methanol (4 x 80 ml) and dichloromethane (7 x 80 ml). The product was cleaved from resin by treatment with 2,2,2-trifluoroethanol (80 ml) for 18 hours. Resin was filtered off and washed with dichloromethane (4 x 80 ml), dichloromethane/2propanol mixture (1: 1, 4 x 80 ml), 2-propanol (2 x 80 ml) and dichloromethane (6 x 80 ml). Solutions were combined; solvent evaporated and crude product was purified by column chromatography (Silicagel 60, 0.040-0-063 mm; eluent: 5 dichloromethane/methanol 1:0-9:1).Intermediate (2) was dried in vacuo and obtained as oil. Yield: 8.20 g (80%). RF (Si02, dichloromethane/methanol 9: 1): 0.20. lH NMR spectrum (300 MHz, CDC13, dH): 7.44-7.33 (m, 1 H); 7.07-6.97 (m, 1 H); 6.7210 6.63 (m, 1 H); 5.70-5.59 (m, 1 H); 4.44-4.33 (m, 1 H); 4.15 (s, 2 H); 4.01 (s, 2 H); 3.76-3.32 (m, 16 H); 3.14-3.07 (m, 2 H); 2.38-1.77 (m, 11 H); 1.71-1.50 (m, 4 H); 1.46 (s, 9 H); 1.44 (s, 9 H); 1.25 (bs, 20 H); 1.05-0.87 (m, 2 H). LC-MS purity: 100%. LC-MS Rt (Sunfire 4.6 mm x 100 mm, acetonitrile/water 50:50 to 100:0 + 0.1% FA): 15 3.56 min. LC-MS m/z: 959.0 (M+H)+.
  • 24
  • [ 843666-40-0 ]
  • C49H47N2O6Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 79-08-3 ]
  • [ 188715-40-4 ]
  • [ 166108-71-0 ]
  • 18-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-[(2-bromoacetyl)amino]-1-carboxypentyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]carbamoyl]cyclohexyl]methylamino]-18-oxooctadecanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% Synthetic protocol: Wang Fmoc-Lys(Mtt) resin 0.26 mmol/g (1, 11.7 g, 3.05 mmol) was left to swell in 5 dichloromethane (100 ml) for 45 minutes. Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 90 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). A solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 2.35 g, 6.09 10 mmol), 0-( 6-chlorobenzotriazol-1-yi)-N, N,N', N' -tetramethyluronium tetrafluoroborate (TCTU, 2.17 g, 6.09 mmol) and N,N-diisopropylethylamine (2.12 ml, 12.2 mmol) in N,Ndimethylformamide (100 ml) was added to resin and the mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90 ml) and N,N-dimethylformamide (3 x 90 ml). Fmoc group was 15 removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 90 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of {2-[2-(9Hfluoren-9-ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 2.35 g, 6.09 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium 20 tetrafluoroborate (TCTU, 2.17 g, 6.09 mmol) and N,N-diisopropylethylamine (2.12 ml, 12.2 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90 ml) and N,N-dimethylformamide (3 x 90 ml) to obtain intermediate 1. Fmoc group was removed by treatment with 20% piperidine in N,N25 dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 90 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of (S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 1-tert-butyl ester (Fmoc-LGiu-OtBu, 1.94 g, 4.57 mmol), 0-(6-chloro-benzotriazol-1-yi)N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 1.62 g, 4.57 mmol) and N,N30 diisopropylethylamine (1.43 ml, 8.23 mmol) in N,N-dimethylformamide (100 ml) was wo 2017/220706 PCT/EP2017/065342 72 added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90ml) and N,Ndimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 90 ml). 5 Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of 4-[(9H-fluoren-9ylmethoxycarbonylamino )methyl]cyclohexanecarboxylic acid (<strong>[188715-40-4]Fmoc-Trx-OH</strong>, 1. 73 g, 4. 57 mmol), 0-( 6-chloro-benzotriazol-1-yi)-N,N,N', N'-tetramethyluronium tetrafluoroborate (TCTU, 1.62 g, 4.57 mmol) and N,N-diisopropylethylamine (1.43 ml, 8.23 mmol) in N,N10 dimethylformamide (100 ml) was added to resin and mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90ml) and N,N-dimethylformamide (3 x 90 ml) to obtain intermediate2. Fmoc group was removed by treatment with 20% piperidine in N,Ndimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 50 ml). Resin was washed 15 with N,N-dimethylformamide (3 x 50 ml), 2-propanol (3 x 50 ml) and dichloromethane (3 x 30 ml). Solution of octadecanedioic acid mono-tert-butyl ester (C18(0tBu)-OH, 0.85 g, 2.28 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 0.81 g, 2.28 mmol) and N,N-diisopropylethylamine (0. 72 ml, 4.11 mmol) in N,N-dimethylformamide (50 ml) was added to resin and mixture was 20 shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 50 ml), dichloromethane (3 x 50 ml) and N,N-dimethylformamide (3 x 50 ml). Mtt group was removed by treatment with 80% 1,1,1,3,3,3-hexafluoro-2-propanol in dichloromethane (2 x 10 min, 2 x 30 min, 4 x 50 ml). Resin was washed with dichloromethane (6 x 50 ml). Solution of bromoacetic acid (4.24 g, 30.5 mmol) and 25 N,N '-diisopropylcarbodiimide (DIC, 4.01 ml, 25.9 mmol) in N,N-dimethylformamide (50 ml) was added to resin and mixture was shaken for 45 minutes. Resin was filtered and washed with N,N-dimethylformamide (5 x 50 ml) and dichloromethane (10 x 50 ml). The product was cleaved from resin by treatment with trifluoroacetic acid (50 ml) for 1 hour. Resin was filtered off and washed with trifluoroacetic acid (1 x 25 ml) and 30 dichloromethane (2 x 30 ml). Solutions were combined and solvents were evaporated to dryness giving the compound as thick brownish oil. Yield: 2.18 mg (64%). 1H NMR spectrum (300 MHz, Ac0D-d4, 80C, dH): 4.72-4.55 (m, 2 H); 4.16 (s, 2 H); 4.12 (s, 2 H); 3.80-3.62 (m, 12 H); 3.58-3.44 (m, 4 H); 3.32 (t, J=6.8 Hz, 2 H); 3.15 35 (d, J=6.8 Hz, 2 H); 2.51-2.07 (m, 8 H); 2.01-1.77 (m, 6 H); ...
  • 25
  • [ 683239-16-9 ]
  • C49H47N2O6Pol [ No CAS ]
  • [ 84793-07-7 ]
  • [ 79-08-3 ]
  • [ 188715-40-4 ]
  • [ 166108-71-0 ]
  • 20-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-[(2-bromoacetyl)amino]-1-carboxypentyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]carbamoyl]cyclohexyl]methylamino]-20-oxoicosanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% Synthetic protocol: Wang Fmoc-Lys(Mtt) resin 0.26 mmol/g (1, 11.2 g, 2.90 mmol) was left to swell in dichloromethane (100 ml) for 45 minutes. Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 15 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). A solution of {2-[2-(9H-fluoren-9ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 2.23 g, 5.80 mmol), 0-(6-chlorobenzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 2.06 g, 5.80 mmol) and N,N-diisopropylethylamine (2.02 ml, 11.6 mmol) in N,N20 dimethylformamide (100 ml) was added to resin and the mixture was shaken for 1 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90 ml) and N,N-dimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 ml). Resin was washed with N,N-dimethylformamide (3 x 90 25 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of {2-[2-(9Hfluoren-9-ylmethoxycarbonylamino)-ethoxy]-ethoxy}-acetic acid (Fmoc-OEG-OH, 2.23 g, 5.80 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 2.06 g, 5.80 mmol) and N,N-diisopropylethylamine (2.02 ml, 11.6 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was 30 shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90ml), dichloromethane (3 x 90 ml) and N,N-dimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of (S)-2-(9H5 fluoren-9-ylmethoxycarbonylamino)-pentanedioic acid 1-tert-butyl ester (Fmoc-LGiuOtBu, 1.85 g, 4.35 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'-tetramethyluronium tetrafluoroborate (TCTU, 1.55 g, 4.35 mmol) and N,N-diisopropylethylamine (1.36 ml, 7.82 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was shaken for 1.5 hour. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 10 ml), dichloromethane (3 x 90ml) and N,N-dimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of <strong>[188715-40-4]4-[(9H-fluoren-9-ylmethoxycarbonylamino)methyl]cyclohexanecarboxylic acid</strong> 15 (<strong>[188715-40-4]Fmoc-Trx-OH</strong>, 1.65 g, 4.35 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'tetramethyluronium tetrafluoroborate (TCTU, 1.55 g, 4.35 mmol) and N,Ndiisopropylethylamine (1.36 ml, 7.82 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was shaken for 2 hours. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90ml) and N,N20 dimethylformamide (3 x 90 ml). Fmoc group was removed by treatment with 20% piperidine in N,N-dimethylformamide (1 x 5 min, 1 x 10 min, 1 x 30 min, 3 x 100 ml). Resin was washed with N,N-dimethylformamide (3 x 90 ml), 2-propanol (3 x 90 ml) and dichloromethane (3 x 90 ml). Solution of icosanedioic acid mono-tert-butyl ester (C20(0tBu)-OH, 1. 73 g, 4.35 mmol), 0-(6-chloro-benzotriazol-1-yi)-N,N,N',N'25 tetramethyluronium tetrafluoroborate (TCTU, 1.55 g, 4.35 mmol) and N,Ndiisopropylethylamine (1.36 ml, 7.82 mmol) in N,N-dimethylformamide (100 ml) was added to resin and mixture was shaken for 2 hours. Resin was filtered and washed with N,N-dimethylformamide (3 x 90 ml), dichloromethane (3 x 90 ml), N,Ndimethylformamide (3 x 90 ml) and dichloromethane (3 x 90 ml). Mtt group was 30 removed by treatment with 80% 1,1,1,3,3,3-hexafluoro-2-propanol in dichloromethane (2 x 10 min, 2 x 30 min, 4 x 100 ml). Resin was washed with dichloromethane (6 x 90 ml) and N,N-dimethylformamide (3 x 90 ml). Solution of bromoacetic acid (8.06 g, 58.0 mmol) and N,N '-diisopropylcarbodiimide (DIC, 7.60 ml, 49.3 mmol) in N,Ndimethylformamide (100 ml) was added to resin and mixture was shaken for 40 35 minutes. Resin was filtered and washed with N,N-dimethylformamide (5 x 90 ml) and dichloromethane (12 x 90 ml). The product was cleaved from resin by treatment with trifluoroacetic acid (100 ml) for 1 hour. Resin was filtered off and washed with trifluoroacetic acid (1 x 50 ml) and dichloromethane (7 x 70 ml). Solutions were combined and solvents were evaporated to dryness giving a thick brownish oil. Yield: 3.28 g (98%). 5 1H NMR spectrum (300 MHz, Ac0D-d4, 80 C, dH): 4.68 (dd, J=8.0 and 5.4 Hz, 1 H); 4.60 (dd, J=7.9 and 5.3 Hz, 1 H); 4.16 (s, 2 H); 4.12 (s, 2 H); 3.94 (s, 2 H); 3.81-3.61 (m, 12 H); 3.59-3.44 (m, 4 H); 3.32 (t, J=6.8 Hz, 2 H); 3.14 (d, J=6.8 Hz, 2 H); 2.491.79 (m, 15 H)...
  • 26
  • [ 2424-92-2 ]
  • [ 1172127-44-4 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2,4-dimethylpentanoic acid [ No CAS ]
  • [ 84793-07-7 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-18-9 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-35-0 ]
  • [ 47375-34-8 ]
  • [ 94744-50-0 ]
  • [ 104091-08-9 ]
  • [ 76-05-1 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 166108-71-0 ]
  • Fmoc-Glu(pg)-OH [ No CAS ]
  • Y-Aib-EGT-αMeF(2F)-TSDYSI-αMeL-LDEK((2-[2-(2-aminoethoxy)ethoxy]acetyl)2-(γGlu)-CO-(CH2)18-CO2H)AQ-Aib-EFI-(D-Glu)-YLIEGGPSSGAPPPS-NH2 trifluoroacetic acid salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: The peptide backbone of Peptide 1 is synthesized usingFluorenylrnethyloxycarbonyi (Fmoe)/tert-Butyl (t-Bu) chemistry on a Symphony X peptide synthesizer (Gyros Protein Technologies. Tucson, AZ).The resin consists of 1% DVB cross-linked polystyrene (Fmoc-Rink-MBHA Low Loading resin, 100-200 mesh, EMD Millipore) at a substitution of 0.3-0.4 meq/g.Standard side-chain protecting groups were used. Fmoc-Lys(Mtt)-OH is used for the lysine at position 17 and Boc-Tyr(tBu)-QH) was used for the tyrosine at position 1. Frnoc groups are removed prior to each coupling step (2 x 7 minutes) using 20% piperidine in DMF. All standard amino acid couplings are performed for 1 hour to a primary amine and 3 hour to a secondary amine, using an equal molar ratio of Fmoc amino acid (0.3 mM), diisopropyicarbodiimide (0.9 mM) and Qxyma (0.9 mM), at a 9-fold molar excess over the theoretical peptide loading. Exceptions are couplings to C -methylated amino acids, which are coupled for 3 hours. After completion of the synthesis of the peptide backbone, the resin is thoroughly washed with DCM for 6 times to remove residual DMF. The Mtt protecting group on the lysine at position 17 is selectively removed from the peptide resin using two treatments of 30% hexafuoroisopropanol (Oakwood Chemicals) in DCM (2 x 40-minute treatment).Subsequent attachment of the fatty acid-linker moiety is accomplished by coupling of 2-[2-(2-Fmoc-amino-ethoxy)-ethoxy]-acetic acid (Fmoc-AEEA-OH, ChemPep, hie.), Fmoe-glutamie acid or-t-butyl ester (Fmoc-Glu-OtBu, Ark Pharm, Inc.), eicosanedioic acid (WuXi AppTec, Shanghai, China). 3-Fold excess of reagents (AA: PyAQP: DIPEAM : 1 : 1 mol/mol) are used for each coupling that is I -hour long.After the synthesis is complete, the peptide resin is washed with DCM, and then thoroughly air-dried. The dry' resin is treated with 10 mL of cleavage cocktail(trifuoroaeetie acid: water: triisopropylsilane, 95:2,5:2.5 v/v) for 2 hours at room temperature. The resin is filtered off, washed twice each with 2 mL of neat T'FA, and the combined filtrates are treated with 5-fold excess volume of cold diethyl ether (-20C) to precipitate the crude peptide. The peptide/ether suspension is then centrifuged at 3500 rpm for 2 min to form a solid pellet, the supernatant is decanted, and the solid pellet is triturated with ether two additional times and dried in vacuo. The crude peptide is solubilized in 20% aeetonitrile/20%Acetic acid/60%water and purified by RP- HPLC on a Luna 5 /.mi Phenyl-Hexyl preparative column (21 x 250 mm, Phenomenex) with linear gradients of 100% acetonitrile and 0.1% TF A/ water buffer system (30-50% acetonitrile in 60 min). The purity of peptide is assessed using analytical RP-HPLC and pooling criteria is >95%. The main pool purity of compound 1 is found to be 98.0%. Subsequent lyophilization of the final main product pool yielded the lyophilized peptide TFA salt.The molecular weight is determined by LC- MS (obsd: M+3 =1657.2; Calc M+3=1657.0).
  • 27
  • [ 683239-16-9 ]
  • [ 1172127-44-4 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2,4-dimethylpentanoic acid [ No CAS ]
  • [ 84793-07-7 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-18-9 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-35-0 ]
  • [ 47375-34-8 ]
  • [ 71989-20-3 ]
  • [ 94744-50-0 ]
  • [ 104091-08-9 ]
  • [ 76-05-1 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 166108-71-0 ]
  • Y-Aib-EGT-αMeF(2F)-TSDYSI-αMeL-LDEK((2-[2-(2-aminoethoxy)ethoxy]acetyl)<SUB>2</SUB>-(γ-Glu)-CO-(CH2)<SUB>18</SUB>-CO<SUB>2</SUB>H)AQ-Aib-EFI-(D-Glu)-YLIEGGPSSGAPPPS-NH<SUB>2</SUB><SUB> trifluoroacetic acid salt</SUB> [ No CAS ]
YieldReaction ConditionsOperation in experiment
The peptide backbone of Example 1 is synthesized using Fluorenylmethyloxycarbonyl (Fmoc)/tert-Butyl (t-Bu) chemistry on a Symphony X peptide synthesizer (Gyros Protein Technologies. Tucson, Ariz.). The resin consists of 1% DVB cross-linked polystyrene (Fmoc-Rink-MBHA Low Loading resin, 100-200 mesh, EMD Millipore) at a substitution of 0.3-0.4 meq/g. Standard side-chain protecting groups were used. Fmoc-Lys(Mtt)-OH is used for the lysine at position 17 and Boc-Tyr(tBu)-OH) was used for the tyrosine at position 1. Fmoc groups are removed prior to each coupling step (2×7 minutes) using 20% piperidine in DMF. All standard amino acid couplings are performed for 1 hour to a primary amine and 3 hour to a secondary amine, using an equal molar ratio of Fmoc amino acid (0.3 mM), diisopropylcarbodiimide (0.9 mM) and Oxyma (0.9 mM), at a 9-fold molar excess over the theoretical peptide loading. Exceptions are couplings to Calpha-methylated amino acids, which are coupled for 3 hours. After completion of the synthesis of the peptide backbone, the resin is thoroughly washed with DCM for 6 times to remove residual DMF. The Mtt protecting group on the lysine at position 17 is selectively removed from the peptide resin using two treatments of 300 hexafluoroisopropanol (Oakwood Chemicals) in DCM (2×40-minute treatment). Subsequent attachment of the fatty acid-linker moiety is accomplished by coupling of 2-[2-(2-Fmoc-amino-ethoxy)-ethoxy]-acetic acid (Fmoc-AEEA-OH, ChemPep, Inc.), Fmoc-glutamic acid alpha-t-butyl ester (Fmoc-Glu-OtBu, Ark Pharm, Inc.), mono-OtBu-eicosanedioic acid (WuXi AppTec, Shanghai, China). 3-Fold excess of reagents (AA:PyAOP:DIPEA=1:1:1 mol/mol) are used for each coupling that is 1-hour long. After the synthesis is complete, the peptide resin is washed with DCM, and then thoroughly air-dried. The dry resin is treated with 10 mL of cleavage cocktail (trifluoroacetic acid:water:triisopropylsilane, 95:2.5:2.5 v/v) for 2 hours at room temperature. The resin is filtered off, washed twice each with 2 mL of neat TFA, and the combined filtrates are treated with 5-fold excess volume of cold diethyl ether (-20 C.) to precipitate the crude peptide. The peptide/ether suspension is then centrifuged at 3500 rpm for 2 min to form a solid pellet, the supernatant is decanted, and the solid pellet is triturated with ether two additional times and dried in vacuo. The crude peptide is solubilized in 20% acetonitrile/20% Acetic acid/60% water and purified by RP-HPLC on a Luna 5 mum Phenyl-Hexyl preparative column (21*250 mm, Phenomenex) with linear gradients of 100% acetonitrile and 0.1% TFA/water buffer system (30-50% acetonitrile in 60 min). The purity of peptide is assessed using analytical RP-HPLC and pooling criteria is >95%. The main pool purity of compound 1 is found to be 98.0%. Subsequent lyophilization of the final main product pool yielded the lyophilized peptide TFA salt. The molecular weight is determined by LC-MS (obsd. M+3=1657.2; Calc M+3=1657.0).
 

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