Structure of 3-(Tritylthio)propionic acid
CAS No.: 27144-18-9
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CAS No. : | 27144-18-9 |
Formula : | C22H20O2S |
M.W : | 348.46 |
SMILES Code : | O=C(O)CCSC(C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3 |
MDL No. : | MFCD00237291 |
InChI Key : | AECGEIVNZGQBJT-UHFFFAOYSA-N |
Pubchem ID : | 262767 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335-H413 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 25 |
Num. arom. heavy atoms | 18 |
Fraction Csp3 | 0.14 |
Num. rotatable bonds | 7 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 104.05 |
TPSA ? Topological Polar Surface Area: Calculated from |
62.6 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.89 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
5.05 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
5.08 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
4.81 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
5.15 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
4.6 |
Log S (ESOL):? ESOL: Topological method implemented from |
-5.25 |
Solubility | 0.00195 mg/ml ; 0.00000559 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
Log S (Ali)? Ali: Topological method implemented from |
-6.11 |
Solubility | 0.000273 mg/ml ; 0.000000783 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.74 |
Solubility | 0.00000641 mg/ml ; 0.0000000184 mol/l |
Class? Solubility class: Log S scale |
Poorly soluble |
GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg |
High |
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg |
Yes |
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) |
Yes |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-4.84 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
1.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.56 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.27 |
* 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 |
---|---|---|
Synthesis of the peptide is carried out by a regular stepwise Fmoc SPPS procedure starting from 2-Cl-Trt-chloride resin. The first amino acid (Fmoc-Gly) is loaded on the resin as described in previous examples to obtain a loading of about 0.7 mmol/g of amino acid/resin. After washing of the resin and removal of the Fmoc group by treatment with piperidine/DMF, the second amino acid (Fmoc-Orn(Boc)) is introduced to continue sequence elongation. Fmoc protected amino acids are activated in situ using TBTU/HOBt and subsequently coupled to the resin over about 50 minutes. Diisopropylethylamine or collidine is used during coupling as an organic base. Completion of the coupling is indicated by ninhydrin test. After washing of the resin, the Fmoc protecting group on the alpha-amine is removed with 20% piperidine in DMF for 20 min. These steps are repeated each time with another amino acid according to the peptide sequence. All amino acids used are Fmoc-Nalpha protected. Trifunctional amino acids are side chain protected as follows: Cys(Acm), Thr(tBu), Asn(Trt), and Orn(Boc). Three equivalents of the activated amino acids are used in the coupling reactions. At the end of the synthesis, the peptide-resin is washed with DMF, followed by DCM, and dried under vacuum to obtain dry peptide-resin. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/fBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g-1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 0.5M HATU in DMF, 4eq of 2M DIPEA (double coupling for Tyr). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF. (0835) The sequence of Fmoc protected amino acids and building blocks used are: 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine (0836) 2. (S)-1 ((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid (0837) 3. (((9H-fluoren-9-yl)methoxy)carbonyl)-L-tyrosine (0838) 4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine (0839) 5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid (0840) 6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid (0841) 7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid (0842) 8. (((9H-fluoren-9-yl)methoxy)carbonyl)glycine (0843) 9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine (0844) 10.3-(tritylthio)propanoic acid (0845) At the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et20. The peptide was cleaved from solid support using 50 ml of TFA solution (v/v) (91 % TFA, 5% H2O, 4% TIPS) for approximately 1.5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (399mg), which was used as crude in the next step. LCMS anal calcd. C61 H75F2N15013S2: 1328.48, found: 1328.2 (M+1 )+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/fBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g-1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 1 M Oxyme in DMF, 4eq of 0.5M L/,/V-diisopropylcarbodiimide (DIC) (double coupling for Y01 ). Fmoc deprotection cycles were performed using 20% (VA/) piperidine in DMF. (0856) The sequence of Fmoc protected amino acids and building blocks used are: (0857) 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine 2. (S)-1 ((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2 -carboxylic acid (0858) 3. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-methoxyphenyl)propanoic acid (0859) 4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine (0860) 5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid (0861) 6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid (0862) 7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid (0863) 8. (((9H-fluoren-9-yl)methoxy)carbonyl)-D-alanine (0864) 9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine (0865) 10.3-(tritylthio)propanoic acid (0866) At the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et20. The peptide was cleaved from solid support using 50 ml of TFA solution (v/v) (91 % TFA, 5% H2O, 4% TIPS) for approximately 1.5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (300mg), which was used as crude in the next step. (0867) LCMS anal calcd. C63H79F2N15013S2: 1356.53, found: 1356.9 (M+1 )+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/fBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g_1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 0.5M HATU in DMF, 4eq of 2M DIPEA (double coupling for Tyr). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF. (0284) The sequence of Fmoc protected amino acids and building blocks used were: 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine 2. (S)-1((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid 3. (((9H-fluoren-9-yl)methoxy)carbonyl)-L-tyrosine 4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine 5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid 6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid 7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid 8. (((9H-fluoren-9-yl)methoxy)carbonyl)glycine 9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine 10. 3-(tritylthio)propanoic acid At the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et20. The peptide was cleaved from solid support using 50 ml of TFA solution (v/v) (91 % TFA, 5% H2O, 4% TIPS) for approximately 1.5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (399mg), which was used as crude in the next step. LCMS analysis was calculated for C61 H75F2N15013S2: 1328.48, found: 1328.2 (M+1)+ | ||
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/iBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g_1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 0.5M HATU in DMF, 4eq of 2M DIPEA (double coupling for Tyr). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF. (0775) The sequence of Fmoc protected amino acids and building blocks used were: 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine 2. (S)-1 ((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid 3. (((9H-fluoren-9-yl)methoxy)carbonyl)-L-tyrosine 4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine 5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid 6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid 7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid 8. (((9H-fluoren-9-yl)methoxy)carbonyl)glycine 9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine 10. 3-(tritylthio)propanoic acid At the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et20. The peptide was cleaved from solid support using 50 ml of TFA solution (v/v) (91 % TFA, 5% H20, 4% TIPS) for approximately 1 .5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (399mg), which was used as crude in the next step. LCMS analysis was calculated for C61 H75F2N15013S2: 1328.48, found: 1328.2 (M+1 )+ | ||
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/fBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g_1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 0.5M HATU in DMF, 4eq of 2M DIPEA (double coupling for Tyr). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF. The sequence of Fmoc protected amino acids and building blocks used were: 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine 2. (S)-1((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid 3. (((9H-fluoren-9-yl)methoxy)carbonyl)-L-tyrosine 4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine 5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid 6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid 7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid 8. (((9H-fluoren-9-yl)methoxy)carbonyl)glycine 9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine 10. 3-(tritylthio)propanoic acid At the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et2 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/fBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g_1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 1 M Oxyme in DMF, 4eq of 0.5M A/,//-diisopropylcarbodiimide (DIC) (double coupling for Y01). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF. The sequence of Fmoc protected amino acids and building blocks used were: 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine 2. (S)-1((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid 3. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-methoxyphenyl)propanoic acid 4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine 5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid 6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid 7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid 8. (((9H-fluoren-9-yl)methoxy)carbonyl)-D-alanine 9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine 10. 3-(tritylthio)propanoic acid At the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et2 H2O, 4% TIPS) for approximately 1.5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (300mg), which was used as crude in the next step. LCMS analysis was calculated for C63H79F2N15013S2: 1356.53, found: 1356.9 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/fBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g_1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 0.5M HATU in DMF, 4eq of 2M DIPEA (double coupling for Tyr). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF. The sequence of Fmoc protected amino acids and building blocks used were:1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine 2. (S)-1((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid3. (((9H-fluoren-9-yl)methoxy)carbonyl)-L-tyrosine4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3-yl)propanoic acid8. (((9H-fluoren-9-yl)methoxy)carbonyl)glycine9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine10. 3-(tritylthio)propanoic acidAt the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et20. The peptide was cleaved from solid support using 50 ml of TFA solution (v/v) (91 % TFA, 5%H2O, 4% TIPS) for approximately 1.5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (399mg), which was used as crude in the next step. LCMS analysis was calculated for C61 H75F2N15013S2: 1328.48, found: 1328.2 (M+1)+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/fBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g_1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 1 M Oxyme in DMF, 4eq of 0.5M A/,//-diisopropylcarbodiimide (DIC)(double coupling for Y01). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF.The sequence of Fmoc protected amino acids and building blocks used were: 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine2. (S)-1((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid3. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-methoxyphenyl)propanoic acid4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid8. (((9H-fluoren-9-yl)methoxy)carbonyl)-D-alanine9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine10. 3-(tritylthio)propanoic acidAt the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et20. The peptide was cleaved from solid support using 50 ml of TFA solution (v/v) (91 % TFA, 5%H2O, 4% TIPS) for approximately 1.5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (300mg), which was used as crude in the next step. LCMS analysis was calculated for C63H79F2N15013S2: 1356.53, found: 1356.9 (M+1)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/iBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g_1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 1 M Oxyme in DMF, 4eq of 0.5M A/,A/-diisopropylcarbodiimide (DIC) (double coupling for Y01 ). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF. The sequence of Fmoc protected amino acids and building blocks used were: 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine 2. (S)-1 ((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid 3. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-methoxyphenyl)propanoic acid 4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine 5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid 6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid 7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid 8. (((9H-fluoren-9-yl)methoxy)carbonyl)-D-alanine 9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine 10. 3-(tritylthio)propanoic acid At the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et20. The peptide was cleaved from solid support using 50 ml of TFA solution (v/v) (91 % TFA, 5% H20, 4% TIPS) for approximately 1 .5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (300mg), which was used as crude in the next step. LCMS analysis was calculated for C63H79F2N15013S2: 1356.53, found: 1356.9 (M+1 )+. | ||
The peptide was synthesized on a 0.250 mmol scale on CEM Liberty Blue, Microwave synthesizer using Fmoc/fBu chemistry on PS Rink-Amide MBHA resin, 0.32 mmol g_1. The assembly was performed using single-couplings using 4eq of Fmoc protected amino acid 0.2M in DMF, 4eq of 1 M Oxyme in DMF, 4eq of 0.5M A/,//-diisopropylcarbodiimide (DIC) (double coupling for Y01). Fmoc deprotection cycles were performed using 20% (V/V) piperidine in DMF. The sequence of Fmoc protected amino acids and building blocks used were: 1. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-S-trityl-L-cysteine 2. (S)-1 ((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-2-methylpyrrolidine-2-carboxylic acid 3. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-methoxyphenyl)propanoic acid 4. N-(((9H-fluoren-9-yl)methoxy)carbonyl)-N-trityl-L-histidine 5. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(tert-butoxy)-4-oxobutanoic acid 6. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid 7. (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(5-fluoro-1 H-indol-3- yl)propanoic acid 8. (((9H-fluoren-9-yl)methoxy)carbonyl)-D-alanine 9. N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N6-(tert-butoxycarbonyl)-L-lysine 10. 3-(tritylthio)propanoic acid At the end of the assembly, the resin was washed with DMF, MeOH, DCM, Et20. The peptide was cleaved from solid support using 50 ml of TFA solution (v/v) (91 % TFA, 5% H2O, 4% TIPS) for approximately 1.5 hours, at room temperature. The resin was filtered, washed with TFA and solution concentrated to dryness and lyophilized. Lyophilization afforded Intermediate Compound Int. A (300mg), which was used as crude in the next step. LCMS analysis was calculated for C63H79F2N15013S2: 1356.53, found: 1356.9 (M+1 )+. |
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