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Chemical Structure| 62-57-7 Chemical Structure| 62-57-7
Chemical Structure| 62-57-7

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2-Aminoisobutyric acid is a rare, non-protein amino acid and end-product of pyrimidine metabolism, excreted in urine and found in some antibiotics of fungal origin.

Synonyms: α-Aminoisobutanoic acid; H-Aib-OH; 2-Methylalanine

4.5 *For Research Use Only !

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Product Details of H-Aib-OH

CAS No. :62-57-7
Formula : C4H9NO2
M.W : 103.12
SMILES Code : CC(C(O)=O)(C)N
Synonyms :
α-Aminoisobutanoic acid; H-Aib-OH; 2-Methylalanine
MDL No. :MFCD00008049
InChI Key :FUOOLUPWFVMBKG-UHFFFAOYSA-N
Pubchem ID :6119

Safety of H-Aib-OH

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

Application In Synthesis of H-Aib-OH

* 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 [ 62-57-7 ]

[ 62-57-7 ] Synthesis Path-Downstream   1~19

  • 1
  • [ 96293-17-3 ]
  • [ 302-72-7 ]
  • [ 74-88-4 ]
  • [ 62-57-7 ]
  • 2
  • sulfate diacetonamine [ No CAS ]
  • [ 625-05-8 ]
  • [ 62-57-7 ]
  • 3
  • [ 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+
  • 4
  • [ 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+
  • 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-{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+
  • 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-{(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
  • 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-[[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
  • 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-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
  • 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 ]
  • 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
  • 10
  • [ 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)
  • 11
  • [ 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
  • 12
  • [ 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)
  • 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 ]
  • [ 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
  • 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-[(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
  • 15
  • [ 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
  • 16
  • [ 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)
  • 17
  • [ 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
  • 18
  • [ 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)
  • 19
  • [ 53848-17-2 ]
  • [ 62-57-7 ]
  • 3,3,8-trimethyl-3,4-dihydroquinoxalin-2(1H)-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With potassium phosphate; copper(l) iodide; In dimethyl sulfoxide; at 140℃; for 16h;Inert atmosphere; Sealed tube; Step 1: A suspension of <strong>[53848-17-2]2-bromo-6-methylaniline</strong> (1.0 g, 54.0 mmol, 1.0 eq) and 2-aminobutyric acid (1.1 g, 10.8 mmol, 2.0 eq) in DMSO (10 ml) in a sealed tube was deoxygenated with Ar for 20 minutes. K3PO4 (2.3 g, 10.8 mmol, 2.0 eq) and CuCl (53.0 mg, 5.4 mmol, 0.1 eq) were then added. The reaction mixture was then stirred at 140 C for 16 h. After completion of the reaction, the reaction mixture was filtered through a celite bed and the celite bed was washed with EtOAc (100 ml). The filtrate was diluted with EtOAc (100 ml) and was washed with water (3 x 150 ml) and brine (200 ml), dried over anhydrous Na2SC>4 and was then evaporated under reduced pressure to obtain the crude compound, which was purified by column chromatography (100-200 mesh silica gel; 30% EtO Ac/hexane; R^ value-0.4) to afford 3,3,8-trimethyl-3,4-dihydroquinoxalin-2(1H)-one (0.6 g, 60%).
 

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