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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Fmoc-N-Me-Leu-OH is an N-Fmoc-N-methylated amino acid used in peptide coupling reactions.
Synonyms: Fmoc-N-Me-Leu-OH
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Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
CAS No. : | 103478-62-2 |
Formula : | C22H25NO4 |
M.W : | 367.44 |
SMILES Code : | CC(C)C[C@@H](C(O)=O)N(C(OCC1C2=CC=CC=C2C3=CC=CC=C13)=O)C |
Synonyms : |
Fmoc-N-Me-Leu-OH
|
MDL No. : | MFCD00151933 |
InChI Key : | BUJQSIPFDWLNDC-FQEVSTJZSA-N |
Pubchem ID : | 7015835 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302+H312+H332-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P305+P351+P338 |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Fmoc-amide resin (0.40 g, 0.25 mmol) was placed in a reaction vessel equipped with a glass filter, and 15 mL of 20percent piperidine in NMP was added thereto and shaken for 20 minutes, thus removing the Fmoc group. Thereafter, 15 mL NMP, 1.0 mmol (4 equivalents) of Fmoc-MeLeu-OH, 1.0 mmol (4 equivalents) of TBTU, 1.0 mmol (4 equivalents) of HOBt and 1.0 mmol (4 equivalents) of DIPEA were added thereto and shaken for 1 hour to condense the Fmoc-MeLeu. Thereafter, the peptide chain was extended by repeatedly carrying out removal of Fmoc group by 20percent piperidine and condensation of Fmoc-amino acid (3 equivalents) by bromo-tris-pyrrolidino-phosphonium hexafluorophosphate (3 equivalents) in the presence of 2.25 mmol (9 equivalents) of DIPEA. The conclusion of the condensation reaction was confirmed by deprotecting a small amount of the resin with TFA and examining it by HPLC and mass spectrometry (MS). After Boc-NH?(CH2)4?CO-Ser (O?C8H17)-MePhe-MeLeu-resin was obtained, this resin was treated with TFA for 30 minutes, whereby the resin was cleaved to de-protect the peptide. After the TFA was evaporated, the peptide was washed with ether (Et2O) to give 120 mg NH2?(CH2)4?CO-Ser(C8H17)-MePhe-MeLeu-NH2. This product was applied to YMC-Pack ODS-A (C18, 20 mm×250 mm) and eluted with a linear gradient (flow rate: 10 mL/min.) for 60 minutes of 0 to 54percent acetonitrile in 0.1percent trifluoroacetic acid. The desired fractions were collected and lyophilized to give 70 mg of the desired product. After this derivative was hydrolyzed with propionic acid-HCl (50/50) at 150° C. for 2 hours, the amount of the peptide was quantified using the ratio of the peak area of aminopentanoic acid detected in the amino acid analyzer to that of 10 nmol aminopentanoic acid as a standard. ESI-MS [M+H]; 604.5 (theoretical: 603.8), detected amino acids after hydrolysis with propionic acid?HCl (50/50) at 150° C. for 2 hours: Ser, Ape. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.5 eq of commercially available Fmoc-NH-OH and DIEA (10 eq) are added to the 2-chlorotrityl resin in 2 mL DCM. The mixture is intermittently stirred manually during 24h. After that, 0.5 mL/g of MeOH are added to the reaction mixture to cap the remaining reactive points of the resin. After 15 minutes, the solution is filtered off and the resin is washed thoroughly with DCM, DMF and MeOH. Fmoc removal is achieved by treating the resin with 20% piperidine in DMF (1 x 5', 1 x 10' and 1 x 15'). For the coupling of Na-Fmoc-NY-alloc-L-2,4-diaminobutyric acid (Fmoc-L-Dab(alloc)-OH), 3 eq of the amino acid, 3 eq of the coupling agent DIC and 3 eq of oxyma pure dissolved in a small amount of DMF and premixed for 2 minutes. The resulting mixture is added to the resin and the reaction is allowed to proceed for 60 minutes. To extent of the reaction is monitored using the Kaiser test. The Fmoc group is then removed by treatments with 20% piperidine in DMF (1 x 5', 1 x 10' and 1 x 15 '). After that, Fmoc- N-methyl-L-iso leucine (Fmoc-NMe-L-Ile-OH) moiety is attached, for that purpose 3 eq of the amino acid, 3 eq of the coupling agent DIC and 3 eq of oxyma pure are dissolved in a small amount of DMF and premixed for 2 minutes. The resulting mixture is added to the resin and the reaction is allowed to proceed for 60 minutes. The extent of the reaction is monitored using the Kaiser test. The Fmoc group is then removed by treatments with 20% piperidine in DMF (1 x 5', 1 x 10' and 1 x 15 '). After that, Fmoc- L-Proline (Fmoc-L-Pro-OH) moiety is attached, for that purpose 3 eq of the amino acid, 3 eq of the coupling agent DIC and 3 eq of oxyma pure are dissolved in a small amount of DMF and premixed for 2 minutes. The resulting the mixture is added to the resin and the reaction is allowed to proceed for 60 minutes. The extent of the reaction is monitored using the Kaiser test. The Fmoc group is then removed by treatments with 20% piperidine in DMF (1 x 5', 1 x 10' and 1 x 15') and additional treatment with a mixture of piperidine/DBU/toluene/DMF (5:5:20:70) (1 x 5'). After that, Fmoc-N- methyl-L-leucine (Fmoc-NMeLeu-OH) moiety is attached, for that purpose 3 eq of the amino acid, 3 eq of the coupling agent DIC and 3 eq of oxyma pure are dissolved in a small amount of DMF and premixed for 2 minutes. The resulting mixture is added to the resin and the reaction is allowed to proceed for 60 minutes. The extent of the reaction is monitored using the Kaiser test. The Fmoc group is then removed by treatments with 20% piperidine in DMF (1 x 5', 1 x 10' and 1 x 15'). After that, Na- Fmoc-N(in)-Boc-N-methyl-L-tryptophan (Fmoc-NMe-L-Trp(Boc)-OH) moiety is attached, for that purpose 3 eq of the amino acid, 3 eq of the coupling agent DIC and 3 eq of oxyma pure are dissolved in a small amount of DMF and premixed for 2 minutes. The resulting mixture is added to the resin and the reaction is allowed to proceed for 60 minutes. The extent of the reaction is monitored using the Kaiser test. The Fmoc group is then removed by treatments with 20% piperidine in DMF (1 x 5', 1 x 10' and 1 x 15'). Butiric acid is coupled to the tryptophan moiety by adding to the resin 3 eq of the acid, 3 eq of the coupling agent DIC and 3 eq of oxyma pure are dissolved in a small amount of DMF and premixed for 2 minutes. The resulting the mixture is added to the resin and the reaction is allowed to proceed for 60 minutes. Then the reaction is filtered off and the resin is rinsed thoroughly with DMF and DCM. The extent of the reaction is monitored using the chloranil test. For the removal of the Alloc group, 10 eq of phenylsilane in DCM are added to the resin while N2 is bubbled through the mixture. Then, 0.1 eq of Pd(PPli3)4 are added maintaining the N2 bubbling while mixing everything well. Then the reaction vessel is sealed and shaken for 15 minutes. After this time, the reaction is filtered and the resin washed thoroughly. The same treatment is repeated two more times. After the last treatment, the resin is washed thoroughly with DCM, MeOH and DMF. For the coupling of the 3,5-difluorobenzoic acid on the side chain of the diaminoethyl moiety, 3 eq of said acid, 3 eq of the coupling agent DIC and 3 eq of oxyma pure dissolved in a small amount of DMF and premixed for 2 minutes. The resulting mixture is added to the resin and the reaction is allowed to proceed for 60 minutes. After this time, the resin is washed with DMF and DCM and the extent of the reaction is monitored the Kaiser test. For the cleavage of the peptide, the resin is washed several times with DCM and dried by suction. The peptide is cleaved from the resin by adding a solution of DCM/TFA (95:5), the mixture is allowed to react for 15 min. Then the reaction mixture is filtered and the resin rinsed with DCM. This cleavage procedure is repeated twice. All the filtrates are pooled and the solvent is evaporated under vacuum, yielding example 14. The compound is purified using reverse-phase chromatography. |