Structure of Fmoc-octyl-D-Gly-OH
CAS No.: 220497-96-1
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CAS No. : | 220497-96-1 |
Formula : | C25H31NO4 |
M.W : | 409.52 |
SMILES Code : | CCCCCCCC[C@@H](NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O)C(O)=O |
MDL No. : | MFCD01311780 |
InChI Key : | LSMLSLHVRMSYPT-HSZRJFAPSA-N |
Pubchem ID : | 2734460 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-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 |
---|---|---|
General procedure: The synthesis was carried out employing a Syro-peptide synthesizer (MultiSynTech) using 24-96 reaction vessels. In each vessel 0.04 mMol of the above resin was placed and the resin was swollen in CH2Cl2 and DMF for 15 min, respectively. The following reaction cycles were programmed and carried out: Unless indicated otherwise, the final coupling of an amino acid was followed by Fmoc deprotection by applying steps 1-3 of the above described reaction cycle. (1485) The appropriately protected amino acid building blocks are commercially available or can be synthesized as known in the art. (1486) Attachment of Carboxylic Acids or Amino Acids to Amino Group- or Carboxylic Group-Bearing Side Chains (1487) Procedure A (1488) Attachment of Carboxylic Acids or Amino Acids to Selectively Deprotected Linear Peptides on Resin: (1489) To remove alloc-protecting groups from amino functions or allyl-protecting groups from carboxy functions present in the resin bound peptide the latter (0.04 mMol) was swollen in freshly distilled CH2Cl2 for at least 15 min followed by adding 0.2 eq tetrakis(triphenyl-phosphine)palladium(0) (10 mM) in dry CH2Cl2 and 10 eq phenylsilane. After shaking the reaction mixture for 15 min at room temperature, the resin was filtered off and a fresh solution of reagents was added to repeat the procedure. Following subsequent washing of the resin with CH2Cl2, DMF and Et2O, the resin was swollen again in CH2Cl2 and the attachment of a carboxylic acid or appropriately protected amino acid was accomplished by subsequently adding a mixture of 3.6 eq of the desired acid and 3.6 eq HOAt dissolved in DMF and 3.6 eq DIC dissolved in DMF allowing the reaction mixture to stand for 1 h disrupted only by occasionally stirring. After filtration and washing of the resin three times with DMF, the coupling was completed by repeating the procedure with a fresh solution of a mixture of 3.6 eq of the same desired acid and 3.6 eq HOAt dissolved in DMF and a mixture of 3.6 eq HATU and 7.2 eq DIPEA in DMF. (1490) In case of amino group-bearing side chains the acids used to be coupled by the above described protocol were octanoic acid or N-Boc protected phenylalanine, in case of carboxy group-bearing side chains the acid coupled by the above described protocol was phenylalanine the carboxy group being protected by tBu. (1491) Cyclization and Work Up of Backbone Cyclized Peptides (1492) Cleavage of the Fully Protected Peptide Fragment (1493) After completion of the synthesis, the resin (0.04 mMol) was suspended in 1 mL (0.13 mMol, 3.4 eq) of 1% TFA in CH2Cl2 (v/v) for 3 minutes, filtered, and the filtrate was neutralized with 1 mL (0.58 mMol, 14.6 eq) of 10% DIEA in CH2Cl2 (v/v). This procedure was repeated three times to ensure completion of the cleavage. The filtrate was evaporated to dryness and a sample of the product was fully deprotected by using a cleavage mixture containing 95% trifluoroacetic acid (TFA), 2.5% water and 2.5% triisopropylsilane (TIS) to be analyzed by reverse phase-HPLC (C18 column) and ESI-MS to monitor the efficiency of the linear peptide synthesis. (1494) Cyclization of the Linear Peptide (1495) The fully protected linear peptide (0.04 mMol) was dissolved in DMF (4 Mol/mL). Then 30.4 mg (0.08 mMol, 2 eq) of HATU, 10.9 mg (0.08 mMol, 2 eq) of HOAt and 28 mul (0.16 mMol, 4 eq) DIEA were added, and the mixture was vortexed at 25 C. for 16 hours and subsequently concentrated under high vacuum. The residue was partitioned between CH2Cl2 and H2O/CH3CN (90/10: v/v). The CH2Cl2 phase was evaporated to yield the fully protected cyclic peptide. (1496) Full Deprotection of the Cyclic Peptide (1497) The cyclic peptide obtained was dissolved in 3 mL of the cleavage mixture containing 82.5% trifluoroacetic acid (TFA), 5% water, 5% thioanisole, 5% phenol and 2.5% ethanedithiole (EDT). The mixture was allowed to stand at 25 C. for 2.5 hours and thereafter concentrated under vacuum. After precipitation of the cyclic fully deprotected peptide in diethylether (Et2O) at 0 C. the solid was washed twice with Et2O and dried. (1498) After purification of the crude products via preparative HPLC the peptides were 20 lyophilized (white powders) and analysed by the following analytical methods: Analytical Method A for Examples 1-17, 19, 39-49 (1499) Analytical HPLC retention times (RT, in minutes) were determined using a Ascentis Express C18 column, 50×3.0 mm, (cod. 53811-U-Supelco) with the following solvents A (H2O+0.1% TFA) and B (CH3CN+0.01% TFA) and the gradient: 0-0.05 min: 97% A, 3% B; 4.95 min: 3% A, 97% B; 5.35 min: 3% A, 97% B; 5.40 min: 97% A, 3% B. Flow rate=1.3 mL/min; UV_Vis=220 nm. Examples 39, 40, 49 are shown in Table 1. The peptides were synthesized as follows: Starting resin was Fmoc-Pro-O-2-chlorotrityl resin, which was prepared as described above. To that resin Xaa7, finally at position 7, was grafted. The linear peptide was synthesized on solid support according to the procedure describe... |
Tags: 220497-96-1 synthesis path| 220497-96-1 SDS| 220497-96-1 COA| 220497-96-1 purity| 220497-96-1 application| 220497-96-1 NMR| 220497-96-1 COA| 220497-96-1 structure
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