Purity | Size | Price | VIP Price | USA Stock *0-1 Day | Global Stock *5-7 Days | Quantity | |||||
{[ item.p_purity ]} | {[ item.pr_size ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} |
{[ getRatePrice(item.pr_usd, 1,1) ]} | Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]} | {[ item.pr_usastock ]} | Inquiry - | {[ item.pr_chinastock ]} | Inquiry - |
* Storage: {[proInfo.prStorage]}
CAS No. : | 105047-45-8 | MDL No. : | MFCD00038539 |
Formula : | C21H24N2O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | YRKFMPDOFHQWPI-IBGZPJMESA-N |
M.W : | 368.43 | Pubchem ID : | 7010557 |
Synonyms : |
|
Num. heavy atoms : | 27 |
Num. arom. heavy atoms : | 12 |
Fraction Csp3 : | 0.33 |
Num. rotatable bonds : | 10 |
Num. H-bond acceptors : | 5.0 |
Num. H-bond donors : | 3.0 |
Molar Refractivity : | 102.3 |
TPSA : | 101.65 Ų |
GI absorption : | High |
BBB permeant : | No |
P-gp substrate : | Yes |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -8.16 cm/s |
Log Po/w (iLOGP) : | 2.3 |
Log Po/w (XLOGP3) : | 0.54 |
Log Po/w (WLOGP) : | 3.11 |
Log Po/w (MLOGP) : | 2.19 |
Log Po/w (SILICOS-IT) : | 2.89 |
Consensus Log Po/w : | 2.2 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 0.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.13 |
Solubility : | 2.71 mg/ml ; 0.00736 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.25 |
Solubility : | 2.09 mg/ml ; 0.00567 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -5.73 |
Solubility : | 0.000684 mg/ml ; 0.00000186 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 2.0 |
Synthetic accessibility : | 3.67 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H332-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
94% | Stage #1: With potassium carbonate In 1,4-dioxane; water at 23℃; for 20 h; Stage #2: With hydrogenchloride In water |
Example L1c (S)-6-Allyloxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid The solution of 25 g (61.7 mmol) of (S)-6-amino-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid in 275 ml of dioxane is mixed with 25 ml of a 25percent potassium carbonate solution, and 6.55 ml of allyl chloroformate is added. It is stirred for 20 hours at 23° C., diluted with water and extracted with methyl-tert-butyl ether. The separated aqueous phase is acidified with a 2N hydrochloric acid and extracted several times with dichloromethane. The combined dichloromethane phases are dried on sodium sulfate. After filtration and removal of the solvent, 26.3 g (58.1 mmol, 94percent) of the title compound, which is further reacted without purification, is isolated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Stage #1: With imidazole-1-sulfonyl azide hydrochloride; potassium carbonate In methanol at 20℃; Stage #2: With hydrogenchloride In dichloromethane; water |
Fmoc-lysine (2.03 g, 5.51 mmol), CuSO4 (88 mg, 0.35 mmol) and K2CO3 (2.46 g, 17.83 mmol) were dissolved in MeOH (70 mL). Imidazole-1-sulfonyl azide hydrochloride (3, 1.40 g, 6.70 mmol) was added in small portions and the suspension was stirred overnight at room temperature. The solvent was evaporated in vacuo, and the residue was redissolved in CH2Cl2 (50 mL). The solution was washed with aqueous HCl (1 M, 50 mL), and the aqueous phase was extracted with CH2Cl2 (3 x 50mL). The crude mixture was purified using gradient column chromatography (CH2Cl2/MeOH/AcOH from 96.5percent/3percent/0.5percent --> 93.5percent/6percent/0.5percent) and lyophilized from dioxane, resulting in a colorless oil (1.94 g, 89percent). In accordance with literature:24 1H-NMR (400 MHz, CDCl3) δ:7.76 (d, J = 7.5 Hz, 2H), 7.59 (d, J= 6.9 Hz, 2H), 7.40 (t, J= 7.5 Hz, 2H), 7.31 (t, J= 7.5 Hz, 2H), 5.34 (d, J = 7.8 Hz, 1H), 4.54 (br s, 1H), 4.43 (d, J = 6.6 Hz, 2H), 4.22 (t, J = 6.6 Hz, 1H), 3.27 (t, J= 6.6 Hz, 2H), 1.3-2.0 (m, 2H). HRMS (ESI+) m/zcalcd for C2,H23N4O8[M+H]+ 395.1719, found 395.1718. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | Fmoc-lysine (2.03 g, 5.51 mmol), CuSO4 (88 mg, 0.35 mmol) and K2CO3 (2.46 g, 17.83 mmol) were dissolved in MeOH (70 mL). Imidazole-1-sulfonyl azide hydrochloride (3, 1.40 g, 6.70 mmol) was added in small portions and the suspension was stirred overnight at room temperature. The solvent was evaporated in vacuo, and the residue was redissolved in CH2Cl2 (50 mL). The solution was washed with aqueous HCl (1 M, 50 mL), and the aqueous phase was extracted with CH2Cl2 (3 x 50mL). The crude mixture was purified using gradient column chromatography (CH2Cl2/MeOH/AcOH from 96.5%/3%/0.5% ? 93.5%/6%/0.5%) and lyophilized from dioxane, resulting in a colorless oil (1.94 g, 89%). In accordance with literature:24 1H-NMR (400 MHz, CDCl3) delta:7.76 (d, J = 7.5 Hz, 2H), 7.59 (d, J= 6.9 Hz, 2H), 7.40 (t, J= 7.5 Hz, 2H), 7.31 (t, J= 7.5 Hz, 2H), 5.34 (d, J = 7.8 Hz, 1H), 4.54 (br s, 1H), 4.43 (d, J = 6.6 Hz, 2H), 4.22 (t, J = 6.6 Hz, 1H), 3.27 (t, J= 6.6 Hz, 2H), 1.3-2.0 (m, 2H). HRMS (ESI+) m/zcalcd for C2,H23N4O8[M+H]+ 395.1719, found 395.1718. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a stirred suspension of Fmoc-Lys (5.1067 g, 13.8618 mmol, 1.0 eq) in methylene chloride (75 ml) at room temperature was added trimethylsilyl chloride (3.8 ml, 29.7312 mmol, 2.14 eq). The mixture was refluxed at 50 C. for 1 hr and the appearance of the solid in the reaction mixture changed. After being cooled in an ice bath, DIEA (7.5 ml, 43.0561 mmol, 3.11 eq) was added, the mixture became homogeneous, and followed by p-anisyldiphenylmethyl chloride (4.4955 g, 14.5580 mmol, 1.05 eq). The orange-red solution was stirred at room temperature overnight (20 hrs). After removal of solvent, the residue was partitioned between ethyl acetate (200 ml) and pH5 buffer (0.05M phthalic acid, adjusted with 10N KOH to pH 5.0). The organic phase was washed with more pH5 buffer (50 ml×2), water (50 ml×1), brine (50 ml×2), dried over magnesium sulfate. After removal of solvent and being dried in vacuo, 9.7336 g of pale yellow foam was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: The peptides are manufactured using Fmoc (9-fluorenylmethyloxycarbonyl) chemistry. Peptides are made using a polystyrene resin, functionalized with an appropriate linker, and the peptides are then manufactured using an lntavis Peptide Synthesizer. A 4-fold excess of amino acid is added relative to the resin and either HATU (O-(7-azabenzotriazol-1 -yl)-N, N, N?, N?-tetramethyluronium hexafluorophosphate)or HCTU (2-(6-Chloro-1 H-benzotriazole-1 -yl)-1 , 1, 3,3-tetramethylaminium hexafluorophosphate) were used at a 3.95-fold excess to create the active ester. Along with an 8-fold excess of DIPEA (N,N-Diisopropylethylamine) as the base, these reagents catalyze the addition of the next amino acid. Once the amino acid is coupled (each cycle includes a double coupling cycle to insure efficient coupling) theresin is exposed to 20% acetic anhydride to terminate (?cap-off?) any peptide chains that have not added the next amino acid.The amino acids are dissolved in NMP (N-Methyl-2- pyrrolidone) or DMF (Dimethylformamide) For washing. Piperidine is used to remove the Fmoc group at theend of each coupling cycle which allows the next amino acid to be added. Similarly the synthesis of BAP modified a-MSH peptide analogues (Example 1)peptides were synthesized using standard Fmoc chemistry using 1-[Bis(dimethylamino)methylene]-1 H-i ,2, 3-triazolo[4, 5-b]pyridinium 3-oxid hexafluorophosphate (HATU) or 2-(6-Chloro-i H-benzotriazole-1 -yl)-l ,1,3,3- tetramethylaminium hexafluorophosphate (HCTU) as the coupling reagents with Hunig?s Base (N,N-diisopropylethylamine, DIPEA). For the lysine branching asdescribed in more detail below, combination of orthogonally protected lysines were used including Fmoc-Lys(MTT)-OH, <strong>[204777-78-6]Fmoc-Lys(ivDde)-OH</strong> , and Fmoc-Lys(Boc)-OH.Peptides were cleaved with standard cleavage cocktails including trifluoroacetic acid, triisoproproylsilane, and water and precipitated with ice-cold ether. All crude peptides were purified by reversed-phase chromatography on columns with C-18 functionalityand using gradients of acetonitrile, deionized water, and trifluoroacetic acid as running buffers. Purity was determined by high-pressure liquid chromatography and mass (MS) and sequence (tandem MS) information was obtained using a nanospray mass spectrometer. BAP attached to lysines in the sequence between the N- and C-terminiMETHOD 2: N - a - Fmoc - N - E - 4 - methyltrityl - L - lysine was added to the peptide sequence, methytrityl was removed after finalizing the sequence and optionally N-terminal acetylation. Appropriate lysine analogues such as Fmoc-Lys(MTT)-OH, FmocLys(ivDde)-OH and Fmoc-Lys(Boc)-OH were sequentially added and selectively deprotected, before acetylation to ensure appropriate side chain and acetyl addition. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Solid phase peptide synthesis was performed on a CEM Liberty Peptide Synthesizer using standard Fmoc chemistry. TentaGel S Ram resin (1 g; 0.25 mmol/g) was swelled in NMP (10 ml) prior to use and transferred between tube and reaction vessel using DCM and NMP. Coupling (0148) An Fmoc-amino acid in NMP/DMF/DCM (1:1:1; 0.2 M; 5 ml) was added to the resin in a CEM Discover microwave unit together with HATU/DMF or COMU/DMF (0.5 M; 2 ml) and DIPEA/NMP (2.0 M; 1 ml). The coupling mixture was heated to 75° C. for 5 min while nitrogen was bubbled through the mixture. The resin was then washed with NMP (4×10 ml). Deprotection (0149) Piperidine/DMF (20percent; 10 ml) was added to the resin for initial deprotection and the mixture was heated by microwaves (30 sec; 40° C.). The reaction vessel was drained and a second portion of piperidine/NMP (20percent; 10 ml) was added and heated (75° C.; 3 min.) again. The resin was then washed with DMF (6×10 ml). Side Chain Acylation (0150) Fmoc-Lys(ivDde)-OH or alternatively another amino acid with an orthogonal side chain protective group was introduced at the position of the acylation. The N-terminal of the peptide backbone was then Boc-protected using Boc2O or alternatively by using a Boc-protected amino acid in the last coupling. While the peptide was still attached to the resin, the orthogonal side chain protective group was selectively cleaved using freshly prepared hydrazine hydrate (2-4percent) in NMP for 2×15 min. The unprotected lysine side chain was first coupled with Fmoc-Glu-OtBu or another spacer amino acid, which was deprotected with piperidine and acylated with a lipophilic moiety using the peptide coupling methodology as described above. Alternatively, the acylation moiety was introduced as a premade building block e.g. Fmoc-Lys(hexadecanoyl-gamma-Glu)-OH where gamm-Glu is the coupling of Glutamic acid through the side-chain. Abbreviations employed are as follows: COMU: 1-[(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)-dimethylamino-morpholinomethylene)]methanaminium hexaflourophosphate ivDde: 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)3-methyl-butyl Dde: 1-(4,4-dimethyl-2,6-dioxocyclohexylidene)-ethyl DCM: dichloromethane DMF: N,N-dimethylformamide (0151) DIPEA: diisopropylethylamine EtOH: ethanol Et2O: diethyl ether HATU: N-[(dimethylamino)-1H-1,2,3-triazol[4,5-b]pyridine-1-ylmethylene]-N-methylmethanaminium hexafluorophosphate N-oxide MeCN: acetonitrile NMP: N-methylpyrrolidone (0152) TFA: trifluoroacetic acid TIS: triisopropylsilane Cleavage (0153) The resin was washed with EtOH (3×10 ml) and Et2O (3×10 ml) and dried to constant weight at room temperature (r.t.). The crude peptide was cleaved from the resin by treatment with TFA/TIS/water (95/2.5/2.5; 40 ml, 2 h; r.t.). Most of the TFA was removed at reduced pressure and the crude peptide was precipitated and washed three times with diethylether and dried to constant weight at room temperature. HPLC Purification of the Crude Peptide (0154) The crude peptide was purified to greater than 90percent by preparative reverse phase HPLC using a PerSeptive Biosystems VISION Workstation equipped with a C-18 column (5 cm; 10 mum) and a fraction collector and run at 35 ml/min with a gradient of buffer A (0.1percent TFA, aq.) and buffer B (0.1percent TFA, 90percent MeCN, aq.). Fractions were analyzed by analytical HPLC and MS and relevant fractions were pooled and lyophilized. The final product was characterized by HPLC and MS. (0155) The synthesized compounds are shown in Table 1 and Table 2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: tGLP-1 and its analogues 2?13 were all synthesized using general solid-phase peptide synthesis of N-Fmoc/tBu chemistry. 63Fmoc Rink Amide-MBHA resin (0.1 mmol) was added to a 25 ml peptide synthetic vessel and swollen with DMF for 40 min. After deprotected by 25percent piperidine in DMF, a solution of Fmoc-AA-OH (0.4 mmol), HATU (0.4 mmol), HoAt (0.4 mmol) and DIPEA (0.8 mmol) in DMF was added to the vessel. After reacted for 1 h, the resin was washed three times with DMF and three times with CH2Cl2, then qualitative ninhydrin testing was performed to monitor whether some free amino groups still existed on the resin ornot. If not, the resin was washed three times with DMF again and repeated the procedures of deprotection and coupling. Forthe coupling of some unnatural amino acids, NMM instead of DIPEA and NMP instead of DMF were used. Besides, the reaction time was prolonged to 4 h. Following the final deprotection of N-terminus, the target peptide was cleaved from resin with Reagent K (TFA/thioanisole/water/phenol/EDT, 82.5:5:5:5:2.5) for 2 h atroom temperature. After filtration, the residue solution was concentrated, precipitated with cold diethyl ether and centrifuged for three times. The residue was dissolved in water and purified by Waters 2545 preparative RP-HPLC system. Sephadex G-25 was used for the further purification to remove some short peptide impurities. The molecular mass of the target peptide was confirmed by MALDI-TOF. The purity of peptide was tested with analytical RP-HPLC, and the conditions were as follows: a linear gradient of 20percent mobile phase A and 80percent mobile phase B to 80percent mobile phase A and 20percent mobile phase B (A: acetonitrile containing 0.1percent TFA; B: H2O containing 0.1percent TFA) in 30 min, at a flow rate of 1 mL/minute with UV detection at 214 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: tGLP-1 and its analogues 2-13 were all synthesized using general solid-phase peptide synthesis of N-Fmoc/tBu chemistry. 63Fmoc Rink Amide-MBHA resin (0.1 mmol) was added to a 25 ml peptide synthetic vessel and swollen with DMF for 40 min. After deprotected by 25% piperidine in DMF, a solution of Fmoc-AA-OH (0.4 mmol), HATU (0.4 mmol), HoAt (0.4 mmol) and DIPEA (0.8 mmol) in DMF was added to the vessel. After reacted for 1 h, the resin was washed three times with DMF and three times with CH2Cl2, then qualitative ninhydrin testing was performed to monitor whether some free amino groups still existed on the resin ornot. If not, the resin was washed three times with DMF again and repeated the procedures of deprotection and coupling. Forthe coupling of some unnatural amino acids, NMM instead of DIPEA and NMP instead of DMF were used. Besides, the reaction time was prolonged to 4 h. Following the final deprotection of N-terminus, the target peptide was cleaved from resin with Reagent K (TFA/thioanisole/water/phenol/EDT, 82.5:5:5:5:2.5) for 2 h atroom temperature. After filtration, the residue solution was concentrated, precipitated with cold diethyl ether and centrifuged for three times. The residue was dissolved in water and purified by Waters 2545 preparative RP-HPLC system. Sephadex G-25 was used for the further purification to remove some short peptide impurities. The molecular mass of the target peptide was confirmed by MALDI-TOF. The purity of peptide was tested with analytical RP-HPLC, and the conditions were as follows: a linear gradient of 20% mobile phase A and 80% mobile phase B to 80% mobile phase A and 20% mobile phase B (A: acetonitrile containing 0.1% TFA; B: H2O containing 0.1% TFA) in 30 min, at a flow rate of 1 mL/minute with UV detection at 214 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Phenethylamine-AMEBA resin (Sigma Aldrich, 0.25 mmol, 1.0 mmol/g) was subjected to solid phase peptide synthesis on an automatic peptide synthesizer (CEM Liberty Blue Microwave) with standard double Arg for the Arg residues and D-Nle andAzidolysine coupled double time. Amino acids were prepared as 0.2 M solution in DMF. A standard coupling cycle was defined as follows:Amino acid coupling: AA (5 eq.), HATU (5 eq.), DIEA (25 eq.)Washing: DMF (3x7 mL)Fmoc Deprotection: 20% Piperidine/0.1 M HOBt (2x7 mL)Washing: DMF (4x7 mL then 1x5 mL) After the assembly of the peptide, the resin was washed with DMF (2x50 mL) and DCM (2x50 mL) then dried under vacuum to give Intermediate 42a (770 mg, 0.250 mmol). Intermediate 42a (770mg, 0.250 mmol) was divided inhalf and each sample was combined with 6 mE TFA solution (37 mE TFA, 1 mE R20, 1 mE TIPS, 2.569 g (20 eq.) DTT) and shaken at ri. for 3 hours. The solution was removed from the resin and precipitated into 40 mE cold Et20. The solution wasvortexed and let stand over ice for 10 minutes before centrifuging at 4000 rpm for 5 minutes. The solvent was removed and the white solid was washed twice more with cold Et20 (40 mE each time), centrifuged (5 minutes each time) and decanted. The solid was dried under vacuum overnight andpurified via M-triggered RPEC yielding Intermediate 43b as a white powder (80 mg, 0.045 mmol, 80%). ECMS (5Q2 ProductAnalysis-Acidic-Peptide-Polar, Acquity UPEC HER C18 column, 130 A, 1.7 tm, 2.1 mmx50 mm, 50 C.):R=2.32 minutes, MS [M+R+2/2] 888.0. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
14% | General procedure: Rink amide MBHA resin (192 mg, 0.1 mmol, 1 .0 eq. , 0.52 mmol g-1 loading) was vortexed in DCM (2.0 ml, 1 min.), allowed to swell (15 mins) and solvent removed. This was followed by addition of DMF (2.0 ml), vortexing (1 min.) and removal of solvent. Deprotection of the Fmoc group was then performed. A solution of 20percent piperidine/DMF (1 .5 ml, v/v) was added to the resin and the subsequent mixture vortexed (2 mins) and solvent removed. This was then repeated a second time with vortexing for 15 minutes. After solvent had been removed, the resin was washed of any unreacted by-products with DMF six times (2.0 ml, vortex 30 s). The desired amino acid or small molecule (Fmoc-AA1 , 0.3 mmol, 3.0 eq.) and coupling reagent (HCTU, 0.12 g, 0.3 mmol, 3.0 eq.) were then dissolved in DMF (1 .5 ml) and added to the deprotected resin. After vortexing (30 s), DIPEA (1 1 1 muIota, 0.6 mmol, 6.0 eq.) was added and the final mixture vortexed (1 -2 hrs). The resin was then washed with DMF (2.0 ml, 30 s vortex) a final four times. The deprotection/coupling cycle was then repeated unless the final amino acid in the sequence had been added, in which case the peptide was washed with DCM five times (2.0 ml, 30 s vortex) and stored in a refrigerator. Removal of the N-terminal Fmoc-group was carried out in the same fashion as the deprotection cycle described previously, with resin washing occurring six times with DMF (2.0 ml, 30 s vortex) and four times with DCM (2.0 ml, 30 s vortex). Successful synthesis of the desired peptide was then ascertained via a microcleave prior to full cleavage of the peptide from the solid-support. This was carried out as follows: a solution of 95percent TFA: 2.5percent (iPr)3SiH: 2.5percent H20 (300 muIota) was added to a small number of resin beads (< 5 mg) and the subsequent mixture vortexed (3 hrs). The clear liquid was then treated with N2 until a small film formed. Analytical HPLC was then performed to determine whether the correct peptide had been synthesized. If the correct peptide had been obtained, a full cleavage was performed using a mixture of 95percent TFA: 2.5percent (iPr)3SiH: 2.5percent H2O (2.0 ml) for 5-6 hrs. The subsequent solution was cooled in an ice-bath alongside 'Bme (40 ml). After 10 minutes, 'Bme (20 ml) was added to the peptide solution, leading to the formation of a white precipitate. The precipitate was cooled further (10 mins) and then centrifuged (7 mins). Decanting of the supernatant was followed by addition of a second aliquot of tBMe (20 ml), vortexing (30 s) and final centrifugation (7 mins). This delivered a white solid which was then freeze-dried (20 mins) to furnish crude peptide. Preparative HPLC was then used to purify the product peptide. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: In a reaction vessel, Fmoc-protected Rink amide MBHA resinwas first swelled in DMF for fifteen min. A solution of 20percent piperidinein DMF was added and mixture shaken mechanically for15 min resulting in the removal of Fmoc group. The required Fmocprotected amino acids and coupling reagent 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) were placed in amino acid vessels sequentially. DMF was added to theamino acid vessel, which was subsequently added (by positivepressure of N2) to the reaction vessel containing the resin, followedby addition of N,N-diisppropylethylamine (DIEA). After 3 h of mechanicalshaking at ambient temperature, the solvent was drainedand the resin washed with DMF (3 x 5 min) followed by methanol(2 x 5 mL). The cycles of deprotection and coupling were repeatedtill the desired peptide chain length was obtained. The resin-boundpeptide was transferred to a round bottom flask, and simultaneousremoval of resin and protective groups was achieved by using acocktail combination of TFA:triisopropylsilane (TIPS):H2O[95:2.5:2.5] for 3 h. The crude peptide was filtered and purified onpreparative HPLC system, and analyzed using solvent system ofCH3CN-H2O-0.1percent CF3COOH in the gradient system: 30 min gradient,30-100percent CH3CN-H2O-0.1percent CF3COOH at 215 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Fmoc-?E-Amc-Ahx-dGlu-dGlu-dGlu-Tyr-Lys-NH2 (SEQ ID NO: 14) was assembled on the resin using standard Fmoc peptide synthesis. The glutamates (dGlu) are D-isomers. Fmoc-?E stands for Fmoc(Glu)-OtBu where the gamma-carboxyl group is unprotected. The last Fmoc on the assembled peptide is then removed by 20percent piperidine. Then a chloroform solution containing 5 eq. of H-Glu(OtBu)-OtBu mixed with 2.5 eq (with respect to H-Glu(OtBu)-OtBu) of diisopropylethylamine was prepared. The solution was then added slowly to 0.25 eq (with respect to H-Glu(OtBu)-OtBu) triphosgene in chloroform over 10 minutes at room temperature. After a 15 minute incubation to allow for isocyanate formation, the reaction is mixed with the ?E-Amc-Ahx-Glu-Glu-Glu-Gly-Tyr-Gly-Gly-Gly-Cys-NH2 (SEQ ID NO: 13) on a rink amide resin pre-swollen in chloroform with 2.5 eq of diisopropylethylamine. After 30 minutes of mixing, a Ninhydrin test was administered to test for residual free-amine on the resin. The reaction was repeated if needed. Once the reaction is complete, the resin is washed and the complete peptide product is cleaved. To couple the purified peptide E?EAmc-Ahx-EEEYK(Bn-NOTA)-NH2 (SEQ ID NO: 15) with SCN-Bn-NOTA (Macrocyclics), E?EAmc-Ahx-dEdEdEYK (SEQ ID NO: 16) was dissolved in DMF at a concentration of 25 mg/mL and an equimolar amount of SCN-Bn-NOTA was dissolved in DMSO at a concentration of 200 mg/mL. After mixing the above DMF and DMSO solutions of the reactants, DIPEA was added to concentration of 2percent v/v. The reaction was monitored by HPLC and allowed to proceed up to 2 hours. Then, glacial acetic acid equivolume to DIPEA is added to stop the reaction. The final product was E?EAmc-Ahx-dGlu-dGlu-dGlu-Tyr-Lys(Bn-NOTA)-NH2 (compound 4) (SEQ ID NO: 8) The product elutes at 14.8 min on an analytical column with a 10percent-90percent gradient in 45 minutes with a flow rate of 0.8 ml/min (A: water with 0.1percent TFA; B: acetonitrile). The mass was verified by MALDI/TOF mass spectrometry?Calculated: 1699.7. found m/z: 1700.7 (M+1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: 100 mg 2-chlorotrityl resin (0.5 mmol/g) was placed in a 6 mL polypropylene syringe with a polyethylene filter in the bottom. It was swelled with DCM for 1 h. Then it was washed by DMF(3 2 mL) and DCM (3 2 mL). The first building block was added by using <strong>[118904-37-3]<strong>[118904-37-3]Fmoc-D-allo-Ile</strong>-OH</strong> (35.3 mg, 0.1 mmol) and DIEA(34.8 mL, 0.2 mmol) in 2 mL DCM and shaken for 1 h. Then 80 mL MeOH was added and shaken for another 20 min. Then the resin was washed by DCM (3 2 mL) and DMF (3 2 mL). The following amino acids were coupled through the general Fmoc-SPPS strategy. Then the resin was treated by a mixture of 3 mL DCM/AcOH/TFE(v/v/v = 8:1:1) for 1.5 h to obtain the crude linear peptide 3(36.7 mg, 0.037 mmol). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
6% | General procedure: The Fmoc-Ala-Wang Resin (0.1mmol/g) was swelled in DCM. The Fmoc group was deprotectedby 20% piperidine in DMF over 2 times. The Fmoc protected amino acid building blocks wereattached to resin by 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3- tetramethyluroniumhexafluorophosphate (HATU, 4 equiv)/1-Hydroxy-7- azabenzotriazole (HOAt, 3.8 equiv) asactivator, N,N-Diisopropylethylamine (DIEA, 8 equiv) as activator base, DMF as solvent for1hour. After coupling all amino acids, the crude peptides were cleaved from resin byTFA/TIS/H2O (88%/6%/6%, v/v/v) for 2 hours, purified by RP-HPLC and identified by ESI-MS.The purification was measured on Shimadzu LC-6AD with preparative C18 column (YMC, Japan,5mum, 20×250 mm), solution A (80% MeCN/H2O with 0.06% TFA) and solution B (100% H2Owith 0.06% TFA). The analysis was measured on Shimadzu LC-2010A with analytic C18 column(YMC, Japan, 5mum, 4.6×150 mm), solution A (80% MeCN/H2O with 0.06% TFA) and solution B(100% H2O with 0.06% TFA). The ESI-MS was measured on Thermo Scientific UltiMate 3000.After RP-HPLC purification, the peptide was obtained by lyophilization. The lyophilizedglycopeptides were redissolved in MeOH/MeONa solution with pH 9.5 to deprotect the acetylgroup on carbohydrate. The glycopeptide was obtained by further RP-HPLC purification andlyophilization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
7% | General procedure: The Fmoc-Ala-Wang Resin (0.1mmol/g) was swelled in DCM. The Fmoc group was deprotectedby 20% piperidine in DMF over 2 times. The Fmoc protected amino acid building blocks wereattached to resin by 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3- tetramethyluroniumhexafluorophosphate (HATU, 4 equiv)/1-Hydroxy-7- azabenzotriazole (HOAt, 3.8 equiv) asactivator, N,N-Diisopropylethylamine (DIEA, 8 equiv) as activator base, DMF as solvent for1hour. After coupling all amino acids, the crude peptides were cleaved from resin byTFA/TIS/H2O (88%/6%/6%, v/v/v) for 2 hours, purified by RP-HPLC and identified by ESI-MS.The purification was measured on Shimadzu LC-6AD with preparative C18 column (YMC, Japan,5mum, 20×250 mm), solution A (80% MeCN/H2O with 0.06% TFA) and solution B (100% H2Owith 0.06% TFA). The analysis was measured on Shimadzu LC-2010A with analytic C18 column(YMC, Japan, 5mum, 4.6×150 mm), solution A (80% MeCN/H2O with 0.06% TFA) and solution B(100% H2O with 0.06% TFA). The ESI-MS was measured on Thermo Scientific UltiMate 3000.After RP-HPLC purification, the peptide was obtained by lyophilization. The lyophilizedglycopeptides were redissolved in MeOH/MeONa solution with pH 9.5 to deprotect the acetylgroup on carbohydrate. The glycopeptide was obtained by further RP-HPLC purification andlyophilization. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | General procedure: Peptides 4 and 5 were synthesized using standard SPPS on Rink Amide high yield resin (loading=0.45mmol/g). The beads were swollen in DMF for 1 hr prior to coupling. Each peptide bond formation was done with 3eq. of the Fmoc protected amino acid, 3eq. of COMU coupling reagent, and 6eq. of DIEA in DMF. Reaction was mixed constantly at room temperature for 30-60min and monitored by Kaiser test. Beads were washed with DMF (3×) MeOH (3×) DMF (3×) after coupling. The N-terminus Fmoc deprotection was done in 1:4 piperidine:DMF mixed constantly for 30min at room temperature. Beads were washed with DMF (6×) after deprotection. The peptide was cleaved from the bead using the cleavage cocktail TFA:H2O:TIPS=95:2.5:2.5 by volume. The TFA was evaporated and cold diethyl ether was added to precipitate peptide. The solution was centrifuged at 4000rpm at 4C for 10min and decanted (3× in cold ether). The peptide was dissolved in water for reverse-phase HPLC purification (ACN/H2O). |
Tags: 105047-45-8 synthesis path| 105047-45-8 SDS| 105047-45-8 COA| 105047-45-8 purity| 105047-45-8 application| 105047-45-8 NMR| 105047-45-8 COA| 105047-45-8 structure
[ 121343-82-6 ]
(S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)pentanedioic acid
Similarity: 1.00
[ 1262886-65-6 ]
(S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)nonanoic acid
Similarity: 1.00
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
Home
* Country/Region
* Quantity Required :
* Cat. No.:
* CAS No :
* Product Name :
* Additional Information :