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Chemical Structure| 71989-31-6 Chemical Structure| 71989-31-6
Chemical Structure| 71989-31-6

*Storage: Sealed in dry, 2-8°C.

Fmoc-Pro-OH

CAS No.: 71989-31-6

Fmoc-Pro-OH is a protected proline derivative with the amino group protected by 9-fluorenylmethoxycarbonyl (Fmoc), suitable for peptide synthesis.

4.5 *For Research Use Only !

Cat. No.: A116916 Purity: 98%

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Product Citations

Product Citations

Gardner, Eric D. ; Dimas, Dustin A. ; Finneran, Matthew C. ; Brown, Sara M. ; Burgett, Anthony W. ; Singh, Shanteri

Abstract: Tryprostatin A and B are prenylated, tryptophan-containing, diketopiperazine natural products, displaying cytotoxic activity through different mechanisms of action. The presence of the 6-methoxy substituent on the indole moiety of tryprostatin A was shown to be essential for the dual inhibition of topoisomerase II and tubulin polymerization However, the inability to perform late-stage modification of the indole ring has limited the structure-activity relationship studies of this class of natural products. Herein, we describe an efficient chemoenzymic approach for the late-stage modification of tryprostatin B using a cyclic dipeptide N-prenyltransferase (CdpNPT) from Aspergillus fumigatus, which generates novel analogs functionalized with allylic, benzylic, heterocyclic, and diene moieties. Notably, this biocatalytic functionalizational study revealed high selectivity for the indole C6 position. Seven of the 11 structurally characterized analogs were exclusively C6-alkylated, and the remaining four contained predominant C6-regioisomers. Of the 24 accepted substrates, 10 provided >50% conversion and eight provided 20-50% conversion, with the remaining six giving <20% conversion under standard conditions. This study demonstrates that prenyltransferase-based late-stage diversification enables direct access to previously inaccessible natural product analogs.

Keywords: biocatalysts ; chemoenzymatic synthesis ; late-stage functionalization ; prenyltransferase ; tryprostatin

Purchased from AmBeed: ; ; ; ;

Alternative Products

Product Details of Fmoc-Pro-OH

CAS No. :71989-31-6
Formula : C20H19NO4
M.W : 337.37
SMILES Code : O=C([C@H]1N(C(OCC2C3=C(C4=C2C=CC=C4)C=CC=C3)=O)CCC1)O
MDL No. :MFCD00037122
InChI Key :ZPGDWQNBZYOZTI-SFHVURJKSA-N
Pubchem ID :688135

Safety of Fmoc-Pro-OH

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

Application In Synthesis of Fmoc-Pro-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 [ 71989-31-6 ]

[ 71989-31-6 ] Synthesis Path-Downstream   1~31

  • 1
  • [ 29022-11-5 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 108-24-7 ]
  • [ 198561-07-8 ]
  • Ac-Pro-Asp-Phe-Gly-OH [ No CAS ]
  • 2
  • [ 29022-11-5 ]
  • [ 35661-39-3 ]
  • [ 71989-31-6 ]
  • [ 71989-26-9 ]
  • [ 198561-07-8 ]
  • NH2-Pra-Lys(Boc)-Pra-Pro-Gly-Pra-Ala-Pra-Pro-Gly-OH [ No CAS ]
  • 3
  • [ 29022-11-5 ]
  • [ 35661-39-3 ]
  • [ 71989-31-6 ]
  • [ 198561-07-8 ]
  • NH2-Pra-Ala-Pra-Pro-Gly-Pra-Ala-Pra-Pro-Gly-OH [ No CAS ]
  • 4
  • Fmoc-Leu-Wang resin [ No CAS ]
  • [ 71989-31-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 132684-60-7 ]
  • [ 198561-07-8 ]
  • C43H69N9O9 [ No CAS ]
  • 5
  • Fmoc-Leu-Wang resin [ No CAS ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • [ 1198076-80-0 ]
  • 6
  • [ 2459-05-4 ]
  • C21H20N3O5Pol [ No CAS ]
  • [ 71989-31-6 ]
  • [ 108-24-7 ]
  • [ 198561-07-8 ]
  • [ 1312616-94-6 ]
YieldReaction ConditionsOperation in experiment
General procedure: All aza-peptidyl inhibitors and probes were synthesized by following the previously reported procedures 1, 2 with slight modifications. Fmoc protecting groups from Rink SS resin (0.75 mmol/g) were removed by treatment with 20percent piperidine in DMF for 15 min, followed by three washes with DMF. A 1.2 M solution of bromoacetic acid (10 eq) in NMP and DIC (10 eq) were added to the resin. The resin was shaken 1.5 hrs and washed three times. A solution of Mono-Fmoc protected hydrazide (3 eq) in NMP was added and shaken overnight. Resin loading was determined by Fmoc-quantification (0.2-0.3 mmol/g). A 0.5M solution of N-Fmoc-protected amino acid (3 eq.) and HOBt (3 eq.) in DMF and DIC (3 eq.) were added to the resin. The resin was shaken 1.5-2hrs. For each of the following steps, Fmoc-deprotection and coupling reactions were repeated as described above. Capping of N-terminal amine was achieved by shaking the resin with a 0.5 M solution of acetic anhydride (5 eq.) and DIEA (5 eq.) in DMF for 5 min.
  • 7
  • C21H20N3O5Pol [ No CAS ]
  • [ 71989-31-6 ]
  • [ 108-24-7 ]
  • [ 63734-73-6 ]
  • [ 198561-07-8 ]
  • [ 1361051-69-5 ]
YieldReaction ConditionsOperation in experiment
General procedure: All aza-peptidyl inhibitors and probes were synthesized by following the previously reported procedures 1, 2 with slight modifications. Fmoc protecting groups from Rink SS resin (0.75 mmol/g) were removed by treatment with 20percent piperidine in DMF for 15 min, followed by three washes with DMF. A 1.2 M solution of bromoacetic acid (10 eq) in NMP and DIC (10 eq) were added to the resin. The resin was shaken 1.5 hrs and washed three times. A solution of Mono-Fmoc protected hydrazide (3 eq) in NMP was added and shaken overnight. Resin loading was determined by Fmoc-quantification (0.2-0.3 mmol/g). A 0.5M solution of N-Fmoc-protected amino acid (3 eq.) and HOBt (3 eq.) in DMF and DIC (3 eq.) were added to the resin. The resin was shaken 1.5-2hrs. For each of the following steps, Fmoc-deprotection and coupling reactions were repeated as described above. Capping of N-terminal amine was achieved by shaking the resin with a 0.5 M solution of acetic anhydride (5 eq.) and DIEA (5 eq.) in DMF for 5 min.
  • 8
  • [ 258332-56-8 ]
  • C29H30NO4Pol [ No CAS ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 105047-45-8 ]
  • [ 198561-07-8 ]
  • C44H70N8O10 [ No CAS ]
  • 9
  • Fmoc-Asp(otBu)-Wang resin [ No CAS ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-23-6 ]
  • [ 71989-26-9 ]
  • [ 120791-76-6 ]
  • [ 198561-07-8 ]
  • [ 684270-46-0 ]
  • C135H182N18O23S3 [ No CAS ]
  • 10
  • [ 29022-11-5 ]
  • [ 71989-31-6 ]
  • [ 71989-18-9 ]
  • [ 71989-38-3 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 58-85-5 ]
  • [ 198561-07-8 ]
  • C66H94N20O21S [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: 4.1.1. Peptide synthesis; 4.1.2; Solid-phase peptide synthesis (SPPS) was performed with standardFmoc chemistry on rink amide resin using an automated peptidesynthesizer (Syro I, Multisyntech). The resin was loaded into a5 mL reactor with a frit at the bottom. Swelling was performed bydispensing 1 mL DMF and incubating for 15 min (2) with 10 sshaking every minute. Fmoc deprotection was achieved by treatmentwith 40percent piperidine DMF for 3 min and 20percent piperidine inDMF for 12 min (10 s/min shaking). Peptide couplings were carriedout by double couplings with Fmoc-protected amino acids(5 equiv), HBTU (5 equiv), HOBt (5 equiv) and DIPEA (10 equiv) inDMF for 40 min (10 s/min shaking). At the respective position,Fmoc-F2Pmp-OH (3 equiv) was coupled in DMF (1 mL) by manualaddition using TBTU (3 equiv), HOBt (3 equiv) and DIPEA (6 equiv)for 3 h, after 3 min preactivation. In case of the sequences for which side-chain labeling with biotinor carboxyfluorescein was planned, an additional 4-methyltrityl-(Mtt-) protected lysine was coupled to the N-terminus. Toselectively remove the Mtt group the resin was washed for 1 minwith DCM (3), deprotection was then achieved by treatment with1.8percent TFA in DCM for 3 min (10). During the deprotection the DCMsolution turned yellow.For fluorescein-labeling of the amine side-chain 5(6)-carboxyfluorescein(3 equiv), HATU (3 equiv), HOAt (3 equiv) andDIPEA (6 equiv) were dissolved in DMF and pre-activated for3 min. The solution was aspirated and coupling was allowed toproceed for 1 h. This step was repeated 4 times.For biotin-labeling of the amine side-chain the resin waswashed for 1 min in NMP (3). D-(+)-Biotin (3 equiv), HATU(3 equiv), HOAt (3 equiv) and DIPEA (6 equiv) were dissolved inNMP and pre-activated for 3 min. The solution was aspirated andcoupling was allowed to proceed for 2 h. This step was repeated2 times. N-terminal acetylation (where applicable) was achieved by dispensing800 lL of a mixture of acetic anhydride/pyridine (1:9) andreaction twice for 5 min (10 s/min shaking). After each deprotection,coupling or acetylation step, 5 washings (1 min each) withDMF were performed (10 s/min shaking).After synthesis the resin was transferred in a 5 mL syringeequipped with a frit, washed with DCM for 1 min (3) and driedin high vacuum for at least 30 min. For cleavage 1 mL of a mixtureof TFA and TIS (20:1) was added. The syringe with the mixture waskept on a shaker for 3 h. Then the liquid phase was filtered into20 mL of ice-cold Et2O. Formed precipitate was centrifuged,washed with ice-cold Et2O (2 20 mL) and purified by HPLC. 4.1.2. Azide functionalization of the N-terminus; To the peptides with the longer carbon linker, 6-azidohexanoicacid was coupled (with standard coupling conditions) to the Nterminalamine.The N-terminal amine of the peptides with the shorter linkerwas converted to an azide functionality directly on solid support.Using the compound imidazole-1-sulfonyl-azide*HCl (synthesissee beneath) and modified conditions, which were reported forsolution phase chemistry from Goddard?Borger and Stick:8 Theresin was washed for 1 min each with DCM (2), DCM/MeOH(2) and MeOH (3). Then (for 40 mg resin, loading= 0.62 mmole/g) 1.4 equiv of imidazole-1-sulfonyl-azide*HClin 1 mL MeOH and 100 ll of a saturated and centrifuged solutionof CuSO4*5H2O was added. After 1 min, DIPEA (1.8 equiv) wasadded and the coupling was allowed to proceed for 1 h andrepeated once more with an intermediate washing with MeOH(3 1 min).
  • 11
  • [ 79598-53-1 ]
  • [ 29022-11-5 ]
  • [ 71989-31-6 ]
  • [ 71989-18-9 ]
  • [ 71989-38-3 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 58-85-5 ]
  • [ 198561-07-8 ]
  • C72H105N21O22S [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: 4.1.1. Peptide synthesis; 4.1.2; Solid-phase peptide synthesis (SPPS) was performed with standardFmoc chemistry on rink amide resin using an automated peptidesynthesizer (Syro I, Multisyntech). The resin was loaded into a5 mL reactor with a frit at the bottom. Swelling was performed bydispensing 1 mL DMF and incubating for 15 min (2) with 10 sshaking every minute. Fmoc deprotection was achieved by treatmentwith 40percent piperidine DMF for 3 min and 20percent piperidine inDMF for 12 min (10 s/min shaking). Peptide couplings were carriedout by double couplings with Fmoc-protected amino acids(5 equiv), HBTU (5 equiv), HOBt (5 equiv) and DIPEA (10 equiv) inDMF for 40 min (10 s/min shaking). At the respective position,Fmoc-F2Pmp-OH (3 equiv) was coupled in DMF (1 mL) by manualaddition using TBTU (3 equiv), HOBt (3 equiv) and DIPEA (6 equiv)for 3 h, after 3 min preactivation. In case of the sequences for which side-chain labeling with biotinor carboxyfluorescein was planned, an additional 4-methyltrityl-(Mtt-) protected lysine was coupled to the N-terminus. Toselectively remove the Mtt group the resin was washed for 1 minwith DCM (3), deprotection was then achieved by treatment with1.8percent TFA in DCM for 3 min (10). During the deprotection the DCMsolution turned yellow.For fluorescein-labeling of the amine side-chain 5(6)-carboxyfluorescein(3 equiv), HATU (3 equiv), HOAt (3 equiv) andDIPEA (6 equiv) were dissolved in DMF and pre-activated for3 min. The solution was aspirated and coupling was allowed toproceed for 1 h. This step was repeated 4 times.For biotin-labeling of the amine side-chain the resin waswashed for 1 min in NMP (3). D-(+)-Biotin (3 equiv), HATU(3 equiv), HOAt (3 equiv) and DIPEA (6 equiv) were dissolved inNMP and pre-activated for 3 min. The solution was aspirated andcoupling was allowed to proceed for 2 h. This step was repeated2 times. N-terminal acetylation (where applicable) was achieved by dispensing800 lL of a mixture of acetic anhydride/pyridine (1:9) andreaction twice for 5 min (10 s/min shaking). After each deprotection,coupling or acetylation step, 5 washings (1 min each) withDMF were performed (10 s/min shaking).After synthesis the resin was transferred in a 5 mL syringeequipped with a frit, washed with DCM for 1 min (3) and driedin high vacuum for at least 30 min. For cleavage 1 mL of a mixtureof TFA and TIS (20:1) was added. The syringe with the mixture waskept on a shaker for 3 h. Then the liquid phase was filtered into20 mL of ice-cold Et2O. Formed precipitate was centrifuged,washed with ice-cold Et2O (2 20 mL) and purified by HPLC. 4.1.2. Azide functionalization of the N-terminus; To the peptides with the longer carbon linker, 6-azidohexanoicacid was coupled (with standard coupling conditions) to the Nterminalamine.The N-terminal amine of the peptides with the shorter linkerwas converted to an azide functionality directly on solid support.Using the compound imidazole-1-sulfonyl-azide*HCl (synthesissee beneath) and modified conditions, which were reported forsolution phase chemistry from Goddard?Borger and Stick:8 Theresin was washed for 1 min each with DCM (2), DCM/MeOH(2) and MeOH (3). Then (for 40 mg resin, loading= 0.62 mmole/g) 1.4 equiv of imidazole-1-sulfonyl-azide*HClin 1 mL MeOH and 100 ll of a saturated and centrifuged solutionof CuSO4*5H2O was added. After 1 min, DIPEA (1.8 equiv) wasadded and the coupling was allowed to proceed for 1 h andrepeated once more with an intermediate washing with MeOH(3 1 min).
  • 12
  • [ 29022-11-5 ]
  • Fmoc-F2Pmp-OH [ No CAS ]
  • [ 71989-31-6 ]
  • [ 71989-18-9 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 58-85-5 ]
  • [ 198561-07-8 ]
  • C67H95F2N20O23PS [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: 4.1.1. Peptide synthesis; 4.1.2; Solid-phase peptide synthesis (SPPS) was performed with standardFmoc chemistry on rink amide resin using an automated peptidesynthesizer (Syro I, Multisyntech). The resin was loaded into a5 mL reactor with a frit at the bottom. Swelling was performed bydispensing 1 mL DMF and incubating for 15 min (2) with 10 sshaking every minute. Fmoc deprotection was achieved by treatmentwith 40percent piperidine DMF for 3 min and 20percent piperidine inDMF for 12 min (10 s/min shaking). Peptide couplings were carriedout by double couplings with Fmoc-protected amino acids(5 equiv), HBTU (5 equiv), HOBt (5 equiv) and DIPEA (10 equiv) inDMF for 40 min (10 s/min shaking). At the respective position,Fmoc-F2Pmp-OH (3 equiv) was coupled in DMF (1 mL) by manualaddition using TBTU (3 equiv), HOBt (3 equiv) and DIPEA (6 equiv)for 3 h, after 3 min preactivation. In case of the sequences for which side-chain labeling with biotinor carboxyfluorescein was planned, an additional 4-methyltrityl-(Mtt-) protected lysine was coupled to the N-terminus. Toselectively remove the Mtt group the resin was washed for 1 minwith DCM (3), deprotection was then achieved by treatment with1.8percent TFA in DCM for 3 min (10). During the deprotection the DCMsolution turned yellow.For fluorescein-labeling of the amine side-chain 5(6)-carboxyfluorescein(3 equiv), HATU (3 equiv), HOAt (3 equiv) andDIPEA (6 equiv) were dissolved in DMF and pre-activated for3 min. The solution was aspirated and coupling was allowed toproceed for 1 h. This step was repeated 4 times.For biotin-labeling of the amine side-chain the resin waswashed for 1 min in NMP (3). D-(+)-Biotin (3 equiv), HATU(3 equiv), HOAt (3 equiv) and DIPEA (6 equiv) were dissolved inNMP and pre-activated for 3 min. The solution was aspirated andcoupling was allowed to proceed for 2 h. This step was repeated2 times. N-terminal acetylation (where applicable) was achieved by dispensing800 lL of a mixture of acetic anhydride/pyridine (1:9) andreaction twice for 5 min (10 s/min shaking). After each deprotection,coupling or acetylation step, 5 washings (1 min each) withDMF were performed (10 s/min shaking).After synthesis the resin was transferred in a 5 mL syringeequipped with a frit, washed with DCM for 1 min (3) and driedin high vacuum for at least 30 min. For cleavage 1 mL of a mixtureof TFA and TIS (20:1) was added. The syringe with the mixture waskept on a shaker for 3 h. Then the liquid phase was filtered into20 mL of ice-cold Et2O. Formed precipitate was centrifuged,washed with ice-cold Et2O (2 20 mL) and purified by HPLC. 4.1.2. Azide functionalization of the N-terminus; To the peptides with the longer carbon linker, 6-azidohexanoicacid was coupled (with standard coupling conditions) to the Nterminalamine.The N-terminal amine of the peptides with the shorter linkerwas converted to an azide functionality directly on solid support.Using the compound imidazole-1-sulfonyl-azide*HCl (synthesissee beneath) and modified conditions, which were reported forsolution phase chemistry from Goddard?Borger and Stick:8 Theresin was washed for 1 min each with DCM (2), DCM/MeOH(2) and MeOH (3). Then (for 40 mg resin, loading= 0.62 mmole/g) 1.4 equiv of imidazole-1-sulfonyl-azide*HClin 1 mL MeOH and 100 ll of a saturated and centrifuged solutionof CuSO4*5H2O was added. After 1 min, DIPEA (1.8 equiv) wasadded and the coupling was allowed to proceed for 1 h andrepeated once more with an intermediate washing with MeOH(3 1 min).
  • 13
  • [ 79598-53-1 ]
  • [ 29022-11-5 ]
  • Fmoc-F2Pmp-OH [ No CAS ]
  • [ 71989-31-6 ]
  • [ 71989-18-9 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 58-85-5 ]
  • [ 198561-07-8 ]
  • C73H106F2N21O24PS [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: 4.1.1. Peptide synthesis; 4.1.2; Solid-phase peptide synthesis (SPPS) was performed with standardFmoc chemistry on rink amide resin using an automated peptidesynthesizer (Syro I, Multisyntech). The resin was loaded into a5 mL reactor with a frit at the bottom. Swelling was performed bydispensing 1 mL DMF and incubating for 15 min (2) with 10 sshaking every minute. Fmoc deprotection was achieved by treatmentwith 40percent piperidine DMF for 3 min and 20percent piperidine inDMF for 12 min (10 s/min shaking). Peptide couplings were carriedout by double couplings with Fmoc-protected amino acids(5 equiv), HBTU (5 equiv), HOBt (5 equiv) and DIPEA (10 equiv) inDMF for 40 min (10 s/min shaking). At the respective position,Fmoc-F2Pmp-OH (3 equiv) was coupled in DMF (1 mL) by manualaddition using TBTU (3 equiv), HOBt (3 equiv) and DIPEA (6 equiv)for 3 h, after 3 min preactivation. In case of the sequences for which side-chain labeling with biotinor carboxyfluorescein was planned, an additional 4-methyltrityl-(Mtt-) protected lysine was coupled to the N-terminus. Toselectively remove the Mtt group the resin was washed for 1 minwith DCM (3), deprotection was then achieved by treatment with1.8percent TFA in DCM for 3 min (10). During the deprotection the DCMsolution turned yellow.For fluorescein-labeling of the amine side-chain 5(6)-carboxyfluorescein(3 equiv), HATU (3 equiv), HOAt (3 equiv) andDIPEA (6 equiv) were dissolved in DMF and pre-activated for3 min. The solution was aspirated and coupling was allowed toproceed for 1 h. This step was repeated 4 times.For biotin-labeling of the amine side-chain the resin waswashed for 1 min in NMP (3). D-(+)-Biotin (3 equiv), HATU(3 equiv), HOAt (3 equiv) and DIPEA (6 equiv) were dissolved inNMP and pre-activated for 3 min. The solution was aspirated andcoupling was allowed to proceed for 2 h. This step was repeated2 times. N-terminal acetylation (where applicable) was achieved by dispensing800 lL of a mixture of acetic anhydride/pyridine (1:9) andreaction twice for 5 min (10 s/min shaking). After each deprotection,coupling or acetylation step, 5 washings (1 min each) withDMF were performed (10 s/min shaking).After synthesis the resin was transferred in a 5 mL syringeequipped with a frit, washed with DCM for 1 min (3) and driedin high vacuum for at least 30 min. For cleavage 1 mL of a mixtureof TFA and TIS (20:1) was added. The syringe with the mixture waskept on a shaker for 3 h. Then the liquid phase was filtered into20 mL of ice-cold Et2O. Formed precipitate was centrifuged,washed with ice-cold Et2O (2 20 mL) and purified by HPLC. 4.1.2. Azide functionalization of the N-terminus; To the peptides with the longer carbon linker, 6-azidohexanoicacid was coupled (with standard coupling conditions) to the Nterminalamine.The N-terminal amine of the peptides with the shorter linkerwas converted to an azide functionality directly on solid support.Using the compound imidazole-1-sulfonyl-azide*HCl (synthesissee beneath) and modified conditions, which were reported forsolution phase chemistry from Goddard?Borger and Stick:8 Theresin was washed for 1 min each with DCM (2), DCM/MeOH(2) and MeOH (3). Then (for 40 mg resin, loading= 0.62 mmole/g) 1.4 equiv of imidazole-1-sulfonyl-azide*HClin 1 mL MeOH and 100 ll of a saturated and centrifuged solutionof CuSO4*5H2O was added. After 1 min, DIPEA (1.8 equiv) wasadded and the coupling was allowed to proceed for 1 h andrepeated once more with an intermediate washing with MeOH(3 1 min).
  • 14
  • Fmoc-Leu-Wang resin [ No CAS ]
  • [ 214750-72-8 ]
  • [ 258332-56-8 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • H-propargyl-Gly-N-Me-Arg-Lys-Pro-N-homo-Tyr-Ile-Leu-OH [ No CAS ]
YieldReaction ConditionsOperation in experiment
The solid phase peptide synthesis (SPPS) was performed using a microwave assisted protocol (Discover microwave oven, CEMCorp.) starting from Fmoc-Leu-Wang resin. The reactions were carried out in a silanized glass tube loosely sealed with a silicon septum. Remark: the development of overpressure was avoided by using DMF as the solvent and intermittent cooling in an ethanol-ice bath. The amino acids were incorporated as their commercially available derivatives in the following order: Fmoc-Ile-OH, Fmoc-N-homo-Tyr(tBu)-OH (synthesized according to ref. 18), Fmoc-Pro-OH, Fmoc-Arg(Pbf)-OH, Fmoc-N-Me-Arg(Mtr)-OH and Fmoc-propargyl-Gly-OH. Elongation of the peptide chain was performedby repetitive cycles of Fmoc deprotection and subsequent couplings of the amino acid. Fmoc deprotection was performed by treating the resin with 25% piperidine in DMF (microwave irradiation: 7 5 s, 100 W), followed by washings with DMF (5). In between each irradiation step, cooling of the reaction mixture to a temperature of 10 C was achieved by sufficient agitation in an ethanol-ice bath. Peptide couplings of Fmoc-Ile-OH, Fmoc-Arg(Pbf)-OH and Fmoc-N-Me-Arg(Mtr)-OH were performed employing 5 equiv of each Fmoc-AA/PyBOP/DIPEA and 7.5 equiv 1-hydroxybenzotriazole (HOBt), dissolved in a minimum amount of DMF (irradiation: 20 10 s, 50W and intermittent cooling). Fmoc-N-homo-Tyr(tBu)-OH (3 equiv) was coupled with 3 equiv PyBOP/DIPEA and 4.5 equiv HOBt in DMF. Fmoc-Pro-OH (5 equiv)and Fmoc-propargyl-Gly-OH (5 equiv) were subjected to a double coupling with HATU (5 equiv) and DIPEA (10 equiv) in DMF. After the last acylation step, the N-terminal Fmoc-residue was deprotected, the resin was 10 rinsed with CH2Cl2 and dried in vacuo. The cleavage from the resin was performed using a mixture of trifluoroacetic acid (TFA)/phenol/H2O/triisopropylsilane (TIS) 88:6:4:2 for 4 h, followed by a filtration of the resin. After evaporation of the solvent in vacuo and precipitation in t-butylmethylether, the crude peptides were purified using preparative RP-HPLC (Agilent 1100 preparative series, column Zorbax Eclipse XDB-C8, 21.2 mm, 150 mm, 5 lm particles, flow rate 10 mL/min) with the solvent system 3-35% acetonitrile in water (0.1% HCO2H) in a linear gradient over 18.0 min, tR: 10.5 min. After the separation, the peptide was lyophilized and peptide purity and identity were assessed by analytical HPLC (Agilent 1100 analytical series, equipped with QuatPump and VWD detector; column ZorbaxEclipse XDB-C8 analytical column, 4.6 mm, 150 mm, 5 lm, flow rate 0.5 mL/min) coupled to a Bruker Esquire 2000 mass detector equipped with an ESI-trap. ESI-TOF high mass accuracy and resolution experiments were performed on a BRUKER maXis MS (BrukerDaltonics, Bremen) in the laboratories of the Chair of OrganicChemistry (Prof. Dr. Rik Tykwinski), Department of Pharmacy and Chemistry, Friedrich-Alexander University of Erlangen Nuremberg. Purity: solvent system 1: 10-55% methanol in water (0.1% HCO2H)in a linear gradient over 18 min, tR = 14.6 min (>99 %); solvent system 2: 3-40% acetonitrile in water (0.1% HCO2H) in a linear gradient over 26 min, tR = 15.9 min (>99%). ESI-MS: m/z calcd:940.6, found: 940.6 [M+H]+; HR-ESI-TOF: [M+H]+ calcd forC45H74N13O9: 940.5732, found: 940.5724.
  • 15
  • [ 1026023-54-0 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 71989-31-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-18-9 ]
  • [ 556-08-1 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 109425-51-6 ]
  • [ 116821-47-7 ]
  • [ 198561-07-8 ]
  • [ 334918-39-7 ]
  • C128H218N50O36 [ No CAS ]
  • 16
  • Fmoc-Rink resin [ No CAS ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 71989-31-6 ]
  • [ 198561-07-8 ]
  • Fmoc-Asn-protected [ No CAS ]
  • Fmoc-Trp-protected, Fmoc-Lys-protected [ No CAS ]
  • H-Asn-Leu-Pro-Gly-Pra-Trp-Lys-NH2 [ No CAS ]
  • 17
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 71989-31-6 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 67436-13-9 ]
  • [ 198561-07-8 ]
  • Pra-TLPSTCGAS-CONH<SUB>2</SUB> [ No CAS ]
YieldReaction ConditionsOperation in experiment
All peptides were synthesized on a 0.2 mmol scale using manual Fmoc-SPPS chemistry under flow using a 3 minute cycle for each amino acid. Specifically, all reagents and solvents are delivered to a stainless steel reactor containing resins at a constant flow rate using HPLC pump; temperature of the reactor was maintained at 60 °C during the synthesis using water bath. Procedure for each amino acid coupling cycle included a 30 second coupling with 1 mmol Fmoc-protected amino acid, 1 mmol HBTU, and 500 of diisopropyl ethyl amine (DIEA) in 2.5 mL of DMF at a flow rate of 6 mL/min (note that for coupling of cysteine and tryptophan, 190 of DIEA was used to prevent racemization); 1 minute wash with DMF at a flow rate of 20 mL/min; 20 second deprotection with 50percent (v/v) piperidine in DMF at a flow rate of 20 mL/min; and 1 minute wash with DMF at a flow rate was 20 mL/min. After completion of the stepwise SPPS, the resin was washed thoroughly with DCM and dried under vacuum. The peptide is simultaneously cleaved from the resin and side-chain deprotected by treatment with 2.5percent (v/v) water, 2.5percent (v/v) 1 ,2- ethanedithiol (EDT), and 1percent (v/v) triisoproprylsilane in neat trifluoroacetic acid (TFA) for 2 hours at room temperature. The resulting solution containing peptide was evaporated by blowing a stream of nitrogen gas over its surface for 15 minutes, then triturated and washed with cold diethyl ether three times. The obtained gummy-like solid was dissolved in 50percent H20: 50percent acetonitrile containing 0.1percent TFA and lyophilized. These same solvent compositions were used in majority of experiments and will be referred to as A: 0.1percent TFA in H20 and B: 0.1percent TFA in acetonitrile. c. Peptide Purification The crude peptide was dissolved in 95percent A: 5percent B with 6 M guanidinium hydrochloride and purified by semi-preparative RP-HPLC (Agilent Zorbax SB C18 column: 21.2 x 250 mm, 7 mutaueta, linear gradient: 5-50percent B over 90 min, flow rate: 5 mL/min). 1 of each HPLC fraction was mixed with 1 mu^ of alpha-cyano-4-hydroxycinnamic acid (CHCA) matrix in 75percent A: 25percent B, spotted with MALDI, and checked for fractions with desired molecular mass. The purity of fractions was confirmed by analytical RP-HPLC (Agilent Zorbax SB C3 column: 2.1 x 150 mm, 5 muiotaeta, gradient: 0-2 minutes 5percent B, 2-11 minutes 5- 65percent B, 11-12 minutes 65percent B, flow rate: 0.8 mL/min). HPLC fractions containing only product materials were confirmed by LC-MS analysis, combined, and then lyophilized. Peptides synthesized using fast flow-based SPPS and purified by RP-HPLC are listed in Table SI .
  • 18
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • N4-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-N2-(9-fluorenylmethylcarbonyl)asparagine [ No CAS ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 109425-51-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • KCNTATCATQRLANFLVHSS-(α-propargylglycinyl)-NFGPILPPTNVGS-(N4-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)asparaginyl)-TY-NH2 [ No CAS ]
  • 19
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • N4-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-N2-(9-fluorenylmethylcarbonyl)asparagine [ No CAS ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 109425-51-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • KCNTATCATQRLANFLVHSS-(N4-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)asparaginyl)-NFGPILPPTNVGS-(α-propargylglycinyl)-TY-NH2 [ No CAS ]
  • 20
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 109425-51-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • K-CNTATCATQRLANFLVHSSNNFGPILPPTNVGS-(α-propargylglycinyl)-TY-NH2 [ No CAS ]
  • 21
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 109425-51-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • K-CNTATCATQRLANFLVHSS-(α-propargylglycinyl)-NFGPILPPTNVGS-(α-propargylglycinyl)-TY-NH2 [ No CAS ]
  • 22
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 109425-51-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • KCNTATCATQRLANFLVHSS-(α-propargylglycinyl)-NFGPILPPTNVGSNTY-NH2 [ No CAS ]
  • 23
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid [ No CAS ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • YGGFLRRIRPKLK-Bpa-Pra-NH<SUB>2</SUB> [ No CAS ]
  • 24
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid [ No CAS ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • YGG-Bpa-LRRIRPKLK-Pra-NH<SUB>2</SUB> [ No CAS ]
  • 25
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • 2-([(9H-fluoren-9-yl)methoxy]carbonyl}amino)-3-(4-benzoylphenyl)propanoic acid [ No CAS ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • Pra-Bpa-KYRRIGPRGKL-NH<SUB>2 </SUB> [ No CAS ]
  • 26
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-38-3 ]
  • [ 71989-26-9 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • [ 198561-07-8 ]
  • Fmoc-Phe-(4-N3)-OH [ No CAS ]
  • YGG-ArN<SUB>3</SUB>-LRRIRPKLK-NH<SUB>2</SUB>; ArN<SUB>3 </SUB>= 4-azidophenylalanine [ No CAS ]
  • 27
  • [ 71989-31-6 ]
  • [ 71989-26-9 ]
  • (S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
  • [ 198561-07-8 ]
  • Rink-amide MBHA resin [ No CAS ]
  • C73H91N8O11Pol [ No CAS ]
  • 28
  • [ 159610-89-6 ]
  • [ 29022-11-5 ]
  • [ 35661-39-3 ]
  • C47H62N4O4 [ No CAS ]
  • [ 71989-31-6 ]
  • [ 198561-07-8 ]
  • [ 166108-71-0 ]
  • Fmoc-Glu(Pg)-OH [ No CAS ]
  • Fmoc-Lys(Pg)-OH [ No CAS ]
  • C120H189N27O30 [ No CAS ]
  • 29
  • [ 35661-60-0 ]
  • [ 35661-60-0 ]
  • [ 71989-31-6 ]
  • [ 77128-72-4 ]
  • [ 198561-07-8 ]
  • C38H58N6O8 [ No CAS ]
  • 30
  • [ 35661-60-0 ]
  • [ 94744-50-0 ]
  • [ 71989-31-6 ]
  • [ 143674-78-6 ]
  • [ 198561-07-8 ]
  • cyclo[D-Pro-D-Leu-Aib-Pgl-D-Leu-Tyr] [ No CAS ]
  • 31
  • [ 35661-60-0 ]
  • [ 71989-31-6 ]
  • [ 143674-78-6 ]
  • [ 201864-71-3 ]
  • [ 198561-07-8 ]
  • cyclo[D-Pro-D-Leu-bhA-Pgl-D-Leu-Tyr] [ No CAS ]
 

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