Fmoc-Thr(tBu)-OH | Carboxylic Acids

Structure of Fmoc-Thr(tBu)-OH
CAS No.: 71989-35-0

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Quality Control of [ 71989-35-0 ] Purity: 97% SDS Specification

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Product Details of [ 71989-35-0 ]

CAS No. :	71989-35-0
Formula :	C₂₃H₂₇NO₅
M.W :	397.46
SMILES Code :	C[C@@H](OC(C)(C)C)[C@@H](C(O)=O)NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O
MDL No. :	MFCD00077075

Safety of [ 71989-35-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 71989-35-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	29
Num. arom. heavy atoms	12
Fraction Csp3	0.39
Num. rotatable bonds	9
Num. H-bond acceptors	5.0
Num. H-bond donors	2.0
Molar Refractivity	110.33
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	84.86 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.79
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	3.96
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	4.18
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.62
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.59
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	3.43

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-4.51
Solubility	0.0122 mg/ml ; 0.0000308 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-5.44
Solubility	0.00143 mg/ml ; 0.00000361 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-5.83
Solubility	0.000583 mg/ml ; 0.00000147 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

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	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	Yes
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.91 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.56

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<3.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	4.49

Application In Synthesis of [ 71989-35-0 ]

* 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 [ 71989-35-0 ]

[ 71989-35-0 ] Synthesis Path-Downstream 1~41

1
[ 71989-35-0 ]
[ 135112-28-6 ]
[ 125238-99-5 ]
3-allyloxycarbonylamino-benzoic acid [ No CAS ]
benzoic anhydride [ No CAS ]
p-nitrobenzylamine [ No CAS ]
Bz-Dab-Nva-Thr-(3-aminobenzoyl)-NHCH₂PhNO₂ [ No CAS ]

References: [1]Organic and Biomolecular Chemistry,2003,vol. 1,p. 93 - 99.

2
C₃₃H₃₄N₃O₅Pol [ No CAS ]
[ 29022-11-5 ]
[ 35661-39-3 ]
[ 122889-11-6 ]
[ 35661-40-6 ]
[ 71989-33-8 ]
[ 71989-14-5 ]
[ 71989-18-9 ]
[ 71989-35-0 ]
[ 109425-51-6 ]
His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Ser(OBn)-[2-amino-3-(biphenyl-4-yl)propanoyl]-NH₂ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 7788 - 7799.

3
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 71989-23-6 ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 71989-28-1 ]
[ 132388-59-1 ]
[ 132327-80-1 ]
[ 143824-78-6 ]
Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
[ 198561-07-8 ]
H-(propargylglycyl)-QGTFTSDYSKYLDSRRAQDFVQWLMNTKRNRNNIA-NH₂ [ No CAS ]

References: [1]Journal of Peptide Science,2011,vol. 17,p. 270 - 280.

4
[ 35661-39-3 ]
C₃₆H₃₇N₂O₆Pol [ No CAS ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 132388-59-1 ]
[ 198561-07-8 ]
[ 684270-46-0 ]
C₂₆H₄₅N₉O₉ [ No CAS ]
[ 1372190-73-2 ]
[ 1372190-70-9 ]

Yield	Reaction Conditions	Operation in experiment
		Lys(Boc)-Pra-Asn(Trt)-Thr(tBu)-Ala-Thr(tBu)-Ala(N3)-Ala-Pal-PEG resin (16) (0.498 g, 0.09 mmol) was cleaved with TFA/iPr3SiH/H2O (v/v/v; 95/2.5/2.5, 5.0 mL) for 2 h, peptide was isolated as described in the general section to afford 47.3 mg of crude peptide 17. The crude peptide 17 (16.3 mg) was purified by RP-HPLC on a preparative Phenomenex Gemini C18, column at a flow rate of 5 mL min-1, using a linear gradient of 1percentB to 61percentB over 60 min (ca. 1percentB per minute) and lyophilised to give the title compound 17 as a white amorphous solid (4.9 mg, 18percent).

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 2661 - 2668.

5
[ 35661-39-3 ]
C₃₆H₃₇N₂O₆Pol [ No CAS ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 132388-59-1 ]
[ 198561-07-8 ]
[ 684270-46-0 ]
[ 1372190-73-2 ]
[ 1372190-65-2 ]

Yield	Reaction Conditions	Operation in experiment
		Lys(Boc)-Pra-Asn(Trt)-Thr(tBu)-Ala-Thr(tBu)-Ala(N3)-Ala-Pal-PEG resin (16) (0.498 g, 0.09 mmol) was cleaved with TFA/iPr3SiH/H2O (v/v/v; 95/2.5/2.5, 5.0 mL) for 2 h, peptide was isolated as described in the general section to afford 47.3 mg of crude peptide 17. The crude peptide 17 (16.3 mg) was purified by RP-HPLC on a preparative Phenomenex Gemini C18, column at a flow rate of 5 mL min-1, using a linear gradient of 1percentB to 61percentB over 60 min (ca. 1percentB per minute) and lyophilised to give the title compound 17 as a white amorphous solid (4.9 mg, 18percent). Purified Lys-Pra-Asn-Thr-Ala-Thr-Ala(N3)-Ala-NH2 (17) (4.4 mg, 5.42 x 10-3 mmol) was dissolved in a mixture of water and tert-butyl alcohol (1 : 2.5, 3.5 mL in total). A stock solution of CuSO4 (0.87 mg, 5.42 x 10-3 mmol) and sodium ascorbate (2.68 mg, 13.6 x 10-3 mmol) in water (1.5 mL) was added and the mixture was microwaved for 20 min at 80 °C in a sealed reaction vessel (120 W max) to afford crude peptide (8), containing inseparable dehydroalanine by-product. The crude peptide (8) was purified by RP-HPLC on a preparative Waters XTerra.(R). Prep. C18 column at a flow rate of 10 mL/min, using a linear gradient of 1percentB to 51percentB over 50 min (ca. 1percentB per minute). Fractions were lyophilised to give the title compound 8 as a white amorphous solid (0.7 mg, 18percent), containing inseparable dehydroalanine by-product.

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 2661 - 2668.

6
[ 35661-39-3 ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 132388-59-1 ]
[ 198561-07-8 ]
[ 684270-46-0 ]
[ 1372190-74-3 ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Fmoc SPPS was performed on a Liberty Microwave Peptide Synthesiser (CEM Corporation, Mathews, NC) using the Fmoc/tBu strategy as previously described35 or manually starting from PAL-PEG polystyrene resin (0.21 mmol/g). For manual synthesis the following steps were undertaken: (a) Fmoc deprotection with 20percent piperidine for 5 min, then 15 min, washing with DMF 5.x.; (b) coupling of the Fmoc amino acid (5 equiv) in the presence of HBTU in DMF (4.9 equiv) and iPr2NEt (10 equiv) for 1 h and washing with DMF 5.x.. For coupling of Fmoc-Pra (1.5 equiv) and Fmoc-N3Ala (1.5 equiv), 1.45 equiv of HBTU and 4.5 equiv of iPr2NEt were used. The progress of the acylation step was monitored by the Kaiser test. A minimum amount of DMF was used for dissolution of the Fmoc amino acid. The resulting peptides were cleaved from the resin with simultaneous side chain protecting group removal by treatment with either TFA/iPr3SiH/DODT/H2O (v/v/v/v; 94/1/2.5/2.5), or with TFA/iPr3SiH/H2O (v/v/v; 95/2.5/2.5) for 2 h at room temperature. Crude peptides were precipitated and triturated with cold diethyl ether, isolated (centrifugation), dissolved in 20percent acetonitrile (aq) containing 0.1percent TFA and lyophilized. Analytical RP-HPLC was performed using a Dionex P680 (flow rate of 1 mL/min), or Dionex Ultimate U3000 system (flow rate of 0.5 mL/min or 0.2 mL/min) using Waters XTerra.(R). column (MS C18, 150 mm .x. 4.6 mm; 5 mum) or, Phenomenex Aqua column (C18, 250 mm .x. 4.6 mm; 5mu), or Phenomenex, Gemini column (C18, 50 mm .x. 2.0 mm, 5mu), using gradient systems as indicated in the Supplementary data. The solvent system used was A (0.1percent TFA in H2O) and B (0.1percent TFA in acetonitrile) with detection at 210 nm, 254 nm, and 280 nm****. The ratio of products was determined by integration of spectra recorded at 210 nm. Peptide masses were confirmed by an inline Thermo Finnegan MSQ mass spectrometer using ESI in the positive mode. When appropriate, a Bruker micrOTOF-Q II mass spectrometer was used for ESI-MS analysis (positive mode). Infrared spectra were obtained using a Perkin Elmer Spectrum One Fourier Transform infrared spectrometer with a universal ATR sampling accessory. Peptide purification was performed using a Waters 600E or Dionex Ultimate U3000 system using a Waters XTerra.(R). column (C18, 300 mm .x. 19 mm; 10 mum), or Phenomenex Gemini C18, 250 mm .x. 10 mm; 5 mum column. Gradient systems were adjusted according to the elution profiles and peak profiles obtained from the analytical RP-HPLC chromatograms. Fractions were collected, analysed by either RP-HPLC or ESI-MS, pooled and lyophilised three times from 10 mM aq HCl.

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 2661 - 2668.

7
[ 35661-39-3 ]
[ 71989-26-9 ]
[ 71989-35-0 ]
[ 132388-59-1 ]
[ 198561-07-8 ]
[ 684270-46-0 ]
C₈₅H₁₁₆N₁₅O₁₇Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Fmoc SPPS was performed on a Liberty Microwave Peptide Synthesiser (CEM Corporation, Mathews, NC) using the Fmoc/tBu strategy as previously described35 or manually starting from PAL-PEG polystyrene resin (0.21 mmol/g). For manual synthesis the following steps were undertaken: (a) Fmoc deprotection with 20percent piperidine for 5 min, then 15 min, washing with DMF 5.x.; (b) coupling of the Fmoc amino acid (5 equiv) in the presence of HBTU in DMF (4.9 equiv) and iPr2NEt (10 equiv) for 1 h and washing with DMF 5.x.. For coupling of Fmoc-Pra (1.5 equiv) and Fmoc-N3Ala (1.5 equiv), 1.45 equiv of HBTU and 4.5 equiv of iPr2NEt were used. The progress of the acylation step was monitored by the Kaiser test. A minimum amount of DMF was used for dissolution of the Fmoc amino acid. The resulting peptides were cleaved from the resin with simultaneous side chain protecting group removal by treatment with either TFA/iPr3SiH/DODT/H2O (v/v/v/v; 94/1/2.5/2.5), or with TFA/iPr3SiH/H2O (v/v/v; 95/2.5/2.5) for 2 h at room temperature. Crude peptides were precipitated and triturated with cold diethyl ether, isolated (centrifugation), dissolved in 20percent acetonitrile (aq) containing 0.1percent TFA and lyophilized. Analytical RP-HPLC was performed using a Dionex P680 (flow rate of 1 mL/min), or Dionex Ultimate U3000 system (flow rate of 0.5 mL/min or 0.2 mL/min) using Waters XTerra.(R). column (MS C18, 150 mm .x. 4.6 mm; 5 mum) or, Phenomenex Aqua column (C18, 250 mm .x. 4.6 mm; 5mu), or Phenomenex, Gemini column (C18, 50 mm .x. 2.0 mm, 5mu), using gradient systems as indicated in the Supplementary data. The solvent system used was A (0.1percent TFA in H2O) and B (0.1percent TFA in acetonitrile) with detection at 210 nm, 254 nm, and 280 nm****. The ratio of products was determined by integration of spectra recorded at 210 nm. Peptide masses were confirmed by an inline Thermo Finnegan MSQ mass spectrometer using ESI in the positive mode. When appropriate, a Bruker micrOTOF-Q II mass spectrometer was used for ESI-MS analysis (positive mode). Infrared spectra were obtained using a Perkin Elmer Spectrum One Fourier Transform infrared spectrometer with a universal ATR sampling accessory. Peptide purification was performed using a Waters 600E or Dionex Ultimate U3000 system using a Waters XTerra.(R). column (C18, 300 mm .x. 19 mm; 10 mum), or Phenomenex Gemini C18, 250 mm .x. 10 mm; 5 mum column. Gradient systems were adjusted according to the elution profiles and peak profiles obtained from the analytical RP-HPLC chromatograms. Fractions were collected, analysed by either RP-HPLC or ESI-MS, pooled and lyophilised three times from 10 mM aq HCl.

References: [1]Bioorganic and Medicinal Chemistry,2012,vol. 20,p. 2661 - 2668.

8
(2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid [ No CAS ]
[ 35661-60-0 ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
[ 162558-25-0 ]
C₈₉H₁₅₀N₁₆O₂₅ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 5079 - 5093.

9
[ 35661-60-0 ]
C₂₃H₂₄N₂O₇ [ No CAS ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
C₉₉H₁₅₃N₁₆O₂₇Pol [ No CAS ]

References: [1]Journal of Peptide Science,2015,vol. 21,p. 231 - 235.

10
[ 1360651-24-6 ]
C₂₃H₂₄N₂O₇ [ No CAS ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
C₉₈H₁₄₉N₁₈O₂₇Pol [ No CAS ]

References: [1]Journal of Peptide Science,2015,vol. 21,p. 231 - 235.

11
[ 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 ]

References: [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 5273 - 5278.

12
(2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid [ No CAS ]
[ 929-10-2 ]
[ 35661-60-0 ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
[ 688316-86-1 ]
6-methylheptanoyl-X-T-X-cyclo[X-X-DF-L-X-X-T] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%		General procedure: 2CTC resin (0.47g,loading = 0.53mmol/g ) was swelled in DCM/DMF for 20min before use. Then,Fmoc-Dab-OAll (1mmol, 4 eq), 8 eq. DIEA and 4ml DMF were added to react withresin for 12hr. The resin was capped with 200 mlmethanol to quench the remaining 2-chlorotrityl chloride. Generally, thesubsequent coupling was carried out using a solution of 4 eq. Fmoc-amino acid,3.8 eq. HCTU, and 8 eq. DIEA in DMF at 30 oC. Each coupling steprequired 1hr and the resin was washed by DMF and DCM before Fmoc-deprotection. The Fmoc group wasremoved by treatment with 20% piperidine in DMF twice (5 min, 10 min) followedby DMF and DCM wash. Dde group wasremoved by treatment with 3% NH2NH2/DMF for 20min threetimes. Allyl group wasremoved by treatment with PhSiH3 (10 eq.), Pd(PPh3)4(2 eq.) in 50% DCM/50% DMF for 3 hrs. After deprotection, the resin waswashed with DCM, 0.5% sodium diethyldithiocarbamate in DMF and DMF severaltimes. The finalcyclization step was carried out with 4 eq. PyAOP, 4eq. HOAt and 8eq.NMM for12hr. The cleavage reagentwas chose as TFA/water/TIPS (95/2.5/2.5). It was added into the dry resinprewashed with DCM and the cleavage was carried out for 1.5 hr. The TFAsolution was concentrated by blowing with N2. The crude peptideswere obtained by precipitating with cold diethyl ether, purified bysemi-preparative HPLC and lyophilized to achieve pure product.

References: [1]Tetrahedron Letters,2015,vol. 56,p. 4796 - 4799.

13
(2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid [ No CAS ]
[ 35661-60-0 ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
[ 181954-34-7 ]
[ 688316-86-1 ]
[ 92-92-2 ]
C₅₉H₈₈N₁₆O₁₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%		General procedure: 2CTC resin (0.47g,loading = 0.53mmol/g ) was swelled in DCM/DMF for 20min before use. Then,Fmoc-Dab-OAll (1mmol, 4 eq), 8 eq. DIEA and 4ml DMF were added to react withresin for 12hr. The resin was capped with 200 mlmethanol to quench the remaining 2-chlorotrityl chloride. Generally, thesubsequent coupling was carried out using a solution of 4 eq. Fmoc-amino acid,3.8 eq. HCTU, and 8 eq. DIEA in DMF at 30 oC. Each coupling steprequired 1hr and the resin was washed by DMF and DCM before Fmoc-deprotection. The Fmoc group wasremoved by treatment with 20% piperidine in DMF twice (5 min, 10 min) followedby DMF and DCM wash. Dde group wasremoved by treatment with 3% NH2NH2/DMF for 20min threetimes. Allyl group wasremoved by treatment with PhSiH3 (10 eq.), Pd(PPh3)4(2 eq.) in 50% DCM/50% DMF for 3 hrs. After deprotection, the resin waswashed with DCM, 0.5% sodium diethyldithiocarbamate in DMF and DMF severaltimes. The finalcyclization step was carried out with 4 eq. PyAOP, 4eq. HOAt and 8eq.NMM for12hr. The cleavage reagentwas chose as TFA/water/TIPS (95/2.5/2.5). It was added into the dry resinprewashed with DCM and the cleavage was carried out for 1.5 hr. The TFAsolution was concentrated by blowing with N2. The crude peptideswere obtained by precipitating with cold diethyl ether, purified bysemi-preparative HPLC and lyophilized to achieve pure product.

References: [1]Tetrahedron Letters,2015,vol. 56,p. 4796 - 4799.

14
(2S)-4-[[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]butanoic acid [ No CAS ]
[ 929-10-2 ]
[ 35661-60-0 ]
[ 71989-35-0 ]
[ 35661-60-0 ]
[ 125238-99-5 ]
[ 688316-86-1 ]
polymyxin E₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%		General procedure: 2CTC resin (0.47g,loading = 0.53mmol/g ) was swelled in DCM/DMF for 20min before use. Then,Fmoc-Dab-OAll (1mmol, 4 eq), 8 eq. DIEA and 4ml DMF were added to react withresin for 12hr. The resin was capped with 200 mlmethanol to quench the remaining 2-chlorotrityl chloride. Generally, thesubsequent coupling was carried out using a solution of 4 eq. Fmoc-amino acid,3.8 eq. HCTU, and 8 eq. DIEA in DMF at 30 oC. Each coupling steprequired 1hr and the resin was washed by DMF and DCM before Fmoc-deprotection. The Fmoc group wasremoved by treatment with 20% piperidine in DMF twice (5 min, 10 min) followedby DMF and DCM wash. Dde group wasremoved by treatment with 3% NH2NH2/DMF for 20min threetimes. Allyl group wasremoved by treatment with PhSiH3 (10 eq.), Pd(PPh3)4(2 eq.) in 50% DCM/50% DMF for 3 hrs. After deprotection, the resin waswashed with DCM, 0.5% sodium diethyldithiocarbamate in DMF and DMF severaltimes. The finalcyclization step was carried out with 4 eq. PyAOP, 4eq. HOAt and 8eq.NMM for12hr. The cleavage reagentwas chose as TFA/water/TIPS (95/2.5/2.5). It was added into the dry resinprewashed with DCM and the cleavage was carried out for 1.5 hr. The TFAsolution was concentrated by blowing with N2. The crude peptideswere obtained by precipitating with cold diethyl ether, purified bysemi-preparative HPLC and lyophilized to achieve pure product.

References: [1]Tetrahedron Letters,2015,vol. 56,p. 4796 - 4799.

15
[ 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 ]

Yield	Reaction Conditions	Operation 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 .

References: [1]Patent: WO2015/175941,2015,A1 .Location in patent: Page/Page column 47-48.

16
N-α-(9-fluorenylmethoxycaebonyl)-N-γ-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl]-L-2,4-diaminobutyric acid [ No CAS ]
[ 220497-96-1 ]
Fmoc-Thr(OtBu)-O-Pol [ No CAS ]
Fmoc-Dap(dansyl)-OH [ No CAS ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
C₁₀₂H₁₆₃N₁₈O₂₇PolS [ No CAS ]

References: [1]Antimicrobial Agents and Chemotherapy,2015,vol. 59,p. 7489 - 7496.

17
N-α-(9-fluorenylmethoxycaebonyl)-N-γ-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl]-L-2,4-diaminobutyric acid [ No CAS ]
[ 220497-96-1 ]
Fmoc-Thr(OtBu)-O-Pol [ No CAS ]
Fmoc-D-Dap(dansyl)-OH [ No CAS ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
C₉₉H₁₆₅N₁₈O₂₇PolS [ No CAS ]

References: [1]Antimicrobial Agents and Chemotherapy,2015,vol. 59,p. 7489 - 7496.

18
N-α-(9-fluorenylmethoxycaebonyl)-N-γ-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl]-L-2,4-diaminobutyric acid [ No CAS ]
[ 220497-96-1 ]
Fmoc-Thr(OtBu)-O-Pol [ No CAS ]
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
C₉₅H₁₆₀N₁₇O₂₆Pol [ No CAS ]

References: [1]Antimicrobial Agents and Chemotherapy,2015,vol. 59,p. 7489 - 7496.

19
N-α-(9-fluorenylmethoxycaebonyl)-N-γ-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl]-L-2,4-diaminobutyric acid [ No CAS ]
[ 220497-96-1 ]
Fmoc-Thr(OtBu)-O-Pol [ No CAS ]
[ 35661-60-0 ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
C₁₀₃H₁₇₆N₁₇O₂₆Pol [ No CAS ]

References: [1]Antimicrobial Agents and Chemotherapy,2015,vol. 59,p. 7489 - 7496.

20
C₅₇H₉₄N₁₁O₁₆Pol [ No CAS ]
[ 71989-35-0 ]
[ 125238-99-5 ]
[ 92-92-2 ]
C₆₀H₉₀N₁₆O₁₃ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1068 - 1077.

21
[ 2215-77-2 ]
C₅₇H₉₄N₁₁O₁₆Pol [ No CAS ]
[ 71989-35-0 ]
[ 125238-99-5 ]
C₆₀H₉₀N₁₆O₁₄ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1068 - 1077.

22
C₅₇H₉₄N₁₁O₁₆Pol [ No CAS ]
[ 92-95-5 ]
[ 71989-35-0 ]
[ 125238-99-5 ]
C₆₀H₉₁N₁₇O₁₃ [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1068 - 1077.

23
[ 124-07-2 ]
C₆₅H₁₀₄N₁₁O₁₆Pol [ No CAS ]
[ 71989-35-0 ]
[ 125238-99-5 ]
C₉₉H₁₆₅N₁₆O₂₅Pol [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1068 - 1077.

24
[ 124-07-2 ]
C₆₅H₁₀₄N₁₁O₁₆Pol [ No CAS ]
[ 71989-35-0 ]
[ 125238-99-5 ]
C₉₉H₁₆₅N₁₆O₂₅Pol [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1068 - 1077.

25
[ 124-07-2 ]
C₆₅H₁₀₄N₁₁O₁₆Pol [ No CAS ]
[ 71989-35-0 ]
[ 125238-99-5 ]
C₉₉H₁₆₅N₁₆O₂₅Pol [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1068 - 1077.

26
[ 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 ]

References: [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5238 - 5245.

27
[ 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 ]

References: [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5238 - 5245.

28
[ 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 ]

References: [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5238 - 5245.

29
[ 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 ]

References: [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5238 - 5245.

30
[ 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 ]

References: [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5238 - 5245.

31
N-α-(9-fluorenylmethoxycaebonyl)-N-γ-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl]-L-2,4-diaminobutyric acid [ No CAS ]
[ 504-99-4 ]
Fmoc-Thr(OtBu)-O-Pol [ No CAS ]
[ 71989-35-0 ]
[ 35661-60-0 ]
[ 73724-45-5 ]
[ 125238-99-5 ]
C₈₂H₁₅₁N₁₅O₂₄ [ No CAS ]

References: [1]Journal of Natural Products,2017,vol. 80,p. 1264 - 1274.

32
N-α-(9-fluorenylmethoxycaebonyl)-N-γ-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl]-L-2,4-diaminobutyric acid [ No CAS ]
[ 929-10-2 ]
Fmoc-Thr(OtBu)-O-Pol [ No CAS ]
[ 71989-35-0 ]
[ 35661-60-0 ]
[ 73724-45-5 ]
[ 125238-99-5 ]
C₈₁H₁₄₉N₁₅O₂₄ [ No CAS ]

References: [1]Journal of Natural Products,2017,vol. 80,p. 1264 - 1274.

33
[ 252049-08-4 ]
[ 124-07-2 ]
[ 35661-60-0 ]
[ 71989-35-0 ]
[ 86123-10-6 ]
[ 125238-99-5 ]
[ 198561-07-8 ]
C₈₈H₁₁₉N₁₅O₂₂ [ No CAS ]

References: [1]ACS Infectious Diseases,2017,vol. 3,p. 941 - 954.

34
C₈₅H₁₄₇N₂₀O₁₇PolS₂ [ No CAS ]
[ 71989-35-0 ]
[ 125238-99-5 ]
[ 76-05-1 ]
C₈₆H₁₆₈N₃₂O₂₁*11C₂HF₃O₂ [ No CAS ]