[ CAS No. 104091-09-0 ] {[proInfo.proName]}

Name: 104091-09-0|Fmoc-D-Glu-OH|95%
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Quality Control of [ 104091-09-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 104091-09-0 ]

Product Details of [ 104091-09-0 ]

CAS No. :	104091-09-0	MDL No. :	MFCD09037362
Formula :	C₂₀H₁₉NO₆	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QEPWHIXHJNNGLU-QGZVFWFLSA-N
M.W :	369.37	Pubchem ID :	40501223
Synonyms :	D-Fmoc-glutamic acid

Calculated chemistry of [ 104091-09-0 ]

Physicochemical Properties

Num. heavy atoms :	27
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.25
Num. rotatable bonds :	9
Num. H-bond acceptors :	6.0
Num. H-bond donors :	3.0
Molar Refractivity :	96.56
TPSA :	112.93 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.75 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.99
Log Po/w (XLOGP3) :	2.54
Log Po/w (WLOGP) :	2.84
Log Po/w (MLOGP) :	1.9
Log Po/w (SILICOS-IT) :	2.28
Consensus Log Po/w :	2.31

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	0.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-3.47
Solubility :	0.127 mg/ml ; 0.000343 mol/l
Class :	Soluble
Log S (Ali) :	-4.56
Solubility :	0.0102 mg/ml ; 0.0000276 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-4.65
Solubility :	0.00819 mg/ml ; 0.0000222 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.83

Safety of [ 104091-09-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 104091-09-0 ]

* 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.

Upstream synthesis route of [ 104091-09-0 ]
Downstream synthetic route of [ 104091-09-0 ]

[ 104091-09-0 ] Synthesis Path-Upstream 1~8

1
[ 56-86-0 ]
[ 104091-09-0 ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium carbonate In acetonitrile at 20℃; for 2 h;	General procedure: To a solution of H-Phe-OH (100 mg, 60.5 mmol) in 50 percent MeCN (6.1 mL)were added Fmoc-OPhth (233 mg, 60.5 mmol) and K2CO3 (167 mg, 121 mmol) and stirred at room temperature. After 2 h of stirring saturated sodium bicarbonate solution and H2O were added and the resulting solution was washed with diethyl ether. The aqueous phase is acidified to pH 1 with 1M HCl and extracted with diethyl ether. The organic phase was washed with 1 M HCl, H2O, brine, dried over MgSO4. The filtrate was evaporatedevaporated under reduced pressure to give yellow solid as crude product.

Reference： [1] Tetrahedron Letters, 2017, vol. 58, # 16, p. 1600 - 1603

2
[ 71989-18-9 ]
[ 104091-09-0 ]

Reference： [1] Tetrahedron Letters, 1992, vol. 33, # 37, p. 5441 - 5444
[2] Organic Letters, 2012, vol. 14, # 24, p. 6346 - 6349

3
[ 56-86-0 ]
[ 1131148-55-4 ]
[ 104091-09-0 ]

Reference： [1] Synlett, 2011, # 14, p. 2013 - 2016

4
[ 56-86-0 ]
[ 28920-43-6 ]
[ 104091-09-0 ]

Reference： [1] Journal of the Chinese Chemical Society, 2011, vol. 58, # 4, p. 509 - 515
[2] Soft Matter, 2011, vol. 7, # 19, p. 8913 - 8922

5
[ 28920-43-6 ]
[ 104091-09-0 ]

Reference： [1] Synlett, 2011, # 14, p. 2013 - 2016

6
[ 104091-09-0 ]
[ 107-18-6 ]
[ 144120-54-7 ]

Reference： [1] Synthesis, 2009, # 5, p. 809 - 814

7
[ 104091-09-0 ]
[ 104091-08-9 ]

Reference： [1] Journal of Organic Chemistry, 1986, vol. 51, # 24, p. 4590 - 4594

8
[ 104091-09-0 ]
[ 292150-20-0 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: With dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 8 h; Cooling with ice Stage #2: With ammonia In tetrahydrofuran for 1.5 h; Cooling with ice	Fmoc-D-Glu-OH (59.8 g, 1.0 eq) was dissolved in anhydrous tetrahydrofuran (THF)(324 mL). DCC (40.1 g, 1.2eq) was then added while stirring in ice-water bath. The reaction mixture was allowed to warm to r.t and stirring wasmaintained for additional 8 h to produce 1,3-dicyclohexylurea (DCU). The precipitates were filtered off, and washed withsmall amount THF. Dry ammonia gas was then bubbled through the reactants while stirring in a NaCl salt-ice bath. Thereaction was completed after 1.5 h when no more white solid was precipitated. Still standing for 30 min, small amountMeOH was added to dissolve the solid. The mixture was cooled in a ice-water bath again. Then 2.0 N HCl was addedcarefully and slowly to adjust pH to 2-3. The solvent was evaporated under vacuum. The resulting solid was dissolvedin AcOEt and then washed with diluted HCl, saturated aqueous NaHCO3 solution, and H2O sequentially. The organiclayer was separated and combined, then dried with MgSO4 overnight, filtered and evaporated under vacuum. Thenresidue was recrystallized with ethyl acetate-cyclohexane system. After filtration, 46.5g target product was obtained witha yield of 78percent. m.p.=204~205°C,[α]=-4.2°(C=10mg/mL,DMF). 1H-NMR(500MHz, DMSO): 7.88(2H, d, J=8.0Hz), 7.72(2H, m), 7.42(2H, m), 7.40(1H, m), 7.40(1H, br.s),7.32(2H, m, 7.02(1H, br.s),4.27(2H, m), 4.20(1H, m), 3.93(1H, dd, J=13.5 and 8.5Hz), 2.25(2H, m), 1.89(1H, m),1.73(1H,m). 13C-NMR(125MHz,DMSO): 173.9, 173.4, 155.9, 143.8, 140.7, 127.6, 127.0, 125.3, 120.0, 65.6, 53.8, 46.6,30.4, 27.2. ESI-MS: 369.03 [M+H]+, 759.98 [2M+Na]+. HR-MS(TOF): 369.1448 [M+H]+, 759.2623 [2M+Na]+, C20H20N2O5.

Reference： [1] Patent: EP2612857, 2017, B1, . Location in patent: Paragraph 0102-0107

[ 104091-09-0 ] Synthesis Path-Downstream 1~88

1
[ 96-81-1 ]
[ 104091-09-0 ]
((S)-1-Benzyl-3-imino-2-oxo-propyl)-carbamic acid 9H-fluoren-9-ylmethyl ester [ No CAS ]
Fmoc-Ile-Wang resin [ No CAS ]
(2S,3S)-2-{(S)-3-[(S)-2-((S)-2-Acetylamino-3-methyl-butyrylamino)-4-carboxy-butyrylamino]-4-phenyl-butyrylamino}-3-methyl-pentanoic acid [ No CAS ]

Reference： [1]Tetrahedron Letters,1997,vol. 38,p. 6145 - 6148

2
[ 71989-31-6 ]
[ 104091-09-0 ]
[ 91000-69-0 ]
[ 135273-01-7 ]
Fmoc-Tyr [ No CAS ]
(5S,8R,13R,15aS)-8-{(S)-2-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-5-guanidino-pentanoylamino}-5-(2-carboxy-ethyl)-4,7,15-trioxo-tetradecahydro-10,11-dithia-3a,6,14-triaza-cyclopentacyclotetradecene-13-carboxylic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1997,vol. 40,p. 3359 - 3368

3
[ 26093-31-2 ]
[ 35661-39-3 ]
[ 104091-09-0 ]
[ 144120-53-6 ]
EtOCOCl, Fmoc-W, Ac₂O [ No CAS ]
(S)-4-[(S)-2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-4-{(S)-1-[(S)-2-carboxy-1-(4-methyl-2-oxo-2H-chromen-7-ylcarbamoyl)-ethylcarbamoyl]-ethylcarbamoyl}-butyric acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 1667 - 1672

4
[ 104091-09-0 ]
[ 73724-45-5 ]
[ 79-31-2 ]
PTX₀₀₇₀₁₁ [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2003,vol. 38,p. 345 - 349

5
[ 104091-09-0 ]
[ 73731-37-0 ]
[ 105047-45-8 ]
[ 135112-28-6 ]
(S)-2-[(S)-2-((2S,3R)-2-{(S)-2-[(S)-6-Amino-2-((S)-2,6-diamino-hexanoylamino)-hexanoylamino]-4-carboxy-butyrylamino}-3-hydroxy-butyrylamino)-4-carboxy-butyrylamino]-pentanoic acid [ No CAS ]

Reference： [1]Organic Letters,2004,vol. 6,p. 3429 - 3432

6
C₈₈H₂₈N₂O₄ [ No CAS ]
[ 943302-79-2 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 104091-09-0 ]
[ 73724-45-5 ]
[ 71989-23-6 ]
[ 71989-20-3 ]
C₁₃₈H₁₂₅N₁₉O₂₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
6.8%	With piperidine; chlorotriisopropylsilane; benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; water; benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; 1,8-diazabicyclo[5.4.0]undec-7-ene; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; In dichloromethane; N,N-dimethyl-formamide;	Example 1. Glu-Ile-Ala-Gln-Leu-Glu-Baa-Glu-Ile-Ser-Gln-Leu-Glu-Gln-NH2 (21). The coupling of the first 6 residues was carried out on an automated APEX 396 Multiple Peptide Synthesizer (Advanced ChemTech) under nitrogen flow using a rink amide resin (430 mg, 0.3 mM) as the solid phase. Each coupling uses four-fold excess of the amino acid, and HBTU, HOBt as activators and DIEA as base in a 1:1:1:3 ratio. Fmoc deprotection was performed using 25% piperidine in DMF solution. After the deprotection of the sixth residue (GIu), one sixth of the resin {ca. 0.05 mM) was placed in a 25 mL fritted glass tube, and swollen with DMF (ca. 10 mL). A 3-fold excess of Fmoc-Baa was dissolved in DMF/DCM (2:1) (9 mL) in a second glass vial. The Fmoc-Baa solution was first activated with PyBOP/HOBt/DIEA (1:1:1:2) for 2 minutes, then mixed with the resin in the fritted glass tube, and shaken on an automated shaker for 1 day at room temperature. Then the resin was washed thoroughly with DMF and DCM to remove unreacted Fmoc-Baa, and retransferred in the automated synthesizer reactor. Fmoc removal was performed by the synthesizer using a 5% DBU solution in DMF. The subsequent amino acid couplings were accomplished using the conditions described above. The final peptide was cleaved from the solid support by washing with TFA:TEPS:H2O (98: 1 : 1) (10 mL) for 4 h and a second time for 18 hrs. The crude fractions were washed with Et2O and lyophilized to remove TFA. Purification was carried out on an Varian C4 column using a gradient of TFA (0.1%) in H2O to TFA in IPA (0.1%) over 75 min at flow rate of 5.0 mL-mur1. The elution time was 57 min. Yield: 8.5 mg (6.8%). MALDI-MS: m/z, calculated 2488 (M++Na), found 2489.

Reference： [1]Patent: WO2007/115180,2007,A1 .Location in patent: Page/Page column 11

7
[ 104091-09-0 ]
[ 104091-08-9 ]

Reference： [1]Journal of Organic Chemistry,1986,vol. 51,p. 4590 - 4594

8
[ 201472-66-4 ]
[ 817562-98-4 ]
[ 29022-11-5 ]
[ 35661-60-0 ]
[ 71989-23-6 ]
[ 71989-38-3 ]
[ 103213-32-7 ]
[ 104091-09-0 ]
(2S,4R)-4-tert-butoxy-1-(9H-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid [ No CAS ]
[ 478183-58-3 ]
[ 1023889-17-9 ]

Yield	Reaction Conditions	Operation in experiment
		A. Elongation of the Peptide on the Resin Each amino acid was added to the peptide sequence using standard Fmoc deprotection and coupling conditions. 22.7 g of Rink Amide MBHA resin was added to a 500 mL peptide reaction vessel. Each amino acid was added to the peptide-resin using the following steps: 1. Wash with 20% piperidine in DMF (250 mL×3 min) 2. Deprotect with 20% piperidine in DMF (250 mL×1 hour). 3. Wash with DMF (2×250 mL), DCM (2×250 mL), DMF (2×250 mL). 4. Dissolve amino acid (4 eq.) and 1-hydroxybenzotriazole (4 eq.) in DMF (250 mL). 5. Add amino acid solution to resin, and then add 1,3-diisopropylcarbodiimide (4 eq.). 6. Shake resin with activated amino acid for 18 hours at 250 rpm on an orbital shaker, unless otherwise indicated. 7. Wash the resin with DMF (1×250 mL), DCM (2×250 mL), DMF (3×250 mL). 8. Check coupling using the quantitative ninhydrin test shown below. 9. Cleave a small amount of the peptide from the resin with 90% trifluoroacetic acid 5% triisopropylsilane, and 5% water. Check purity of peptide by analytical HPLC. The following is a list of the amino acids used in the synthesis: Amino Acid Amount Company Catalog No. 1. Pseudotripeptide?* 47.2 g in house synthesis 2. Fmoc-L-Ile-OH 21.2 g Novabiochem 04-12-1024 3. Fmoc-L-Tyr(tBu)-OH 27.6 g Novabiochem 04-12-1037 4. Fmoc-L-Cys(Trt)-OH 35.1 g Novabiochem 04-12-1018 5. Fmoc-L-Leu-OH 21.2 g Novabiochem 04-12-1025 6. Fmoc-L-Gly-OH 17.8 g Novabiochem 04-12-1001 7. Fmoc-L-Tyr(3-Cl)-OH?? 26.3 g in house synthesis 8. Fmoc-L-Hyp(tBu)-OH 24.6 g Novabiochem 04-12-1078 9. Fmoc-L-Cys(Trt)-OH 35.1 g Novabiochem 04-12-1018 10. Fmoc-D-Glu-OH 25.5 g Novabiochem 04-13-1051 11. Fmoc-L-Tyr(tBu)-OH 27.6 g Novabiochem 04-12-1037 12. Boc-L-Dab(Boc)-OH.DCHA 30.0 g Bachem A-3480 The pseudotripeptide was synthesized in house using the procedure shown below. ?The pseudotripeptide was allowed to couple over the weekend for three days. (Previous experience with the synthesis of EP2080 peptide has shown that this longer coupling time was required for the attachment of the first amino acid to the resin). Typically the resin is capped with a solution of 5% acetic anhydride and 6% diisopropylethylamine in DMF after the first coupling. After the coupling of the amino acids is complete, the resin is washed with DMF (3 × 250 mL) and the capping solution (250 mL). The resin is shaken with the capping solution (250 mL) for 1 hour. ??Fmoc-Tyr(3-Cl)-OH was synthesized in house using the procedure shown below.; I. Cleavage, Cyclization and Purification Procedures i. Cleavage After the elongation of the peptide on the resin was complete, the resin was washed with DCM (3×250 mL). The resin was dried under reduced pressure at 22-25 C. for 18 hours. The weight of the dry peptide-resin (57.08 g) was determined. Approximately 15 mL/g (840 mL) of the following cleavage cocktail was added: 80% trifluoroacetic acid, 5% triisopropylsilane, 5% dodecanethiol, 5% dichloromethane, and 5% water. The peptide-resin was shaken for 1.25 hours at room temperature on an orbital shaker (250 rpm), and then filtered and washed with trifluoroacetic acid (2×100 mL). The filtrates were combined and poured into ether (4 L) at 0 C. over 5 minutes to form a precipitate. The precipitate was filtered, washed with ether* (1 L), washed with acetonitrile (1 L), and dried under vacuum. 24.87 g. (73.3% purity by area, Analytical Method 2, 41.4% potency) (40% yield based on potency) *Isopropyl ether has been substituted for diethyl ether successfully on a 2 mmol scale.

Reference： [1]Patent: US2006/155120,2006,A1 .Location in patent: Page/Page column 24; 25; 27

9
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 73731-37-0 ]
[ 88050-17-3 ]
[ 76-05-1 ]
C₂HF₃O₂*C₄₇H₇₂N₁₀O₁₇ [ No CAS ]

Reference： [1]Chemical Communications,2007,p. 4453 - 4455

10
[ 2127-03-9 ]
[ 29022-11-5 ]
[ 2799-07-7 ]
[ 104091-09-0 ]
[ 108-24-7 ]
Fmoc-L [ No CAS ]
Fmoc-K [ No CAS ]
CH₃CO-NH-[GEELLKKLEELLKKGGC]-Spy, M_w = 8700 Da [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2007,vol. 5,p. 3637 - 3650

11
[ 104091-09-0 ]
[ 107-18-6 ]
[ 144120-54-7 ]

Reference： [1]Synthesis,2009,p. 809 - 814

12
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 71989-28-1 ]
[ 71989-16-7 ]
[ 71989-20-3 ]
[ 135112-27-5 ]
MetGlnTyrLysLeuAlaLeuAsnGlyLysThrLeuLysGlyGluThrThrThrGluAlaValAspAlaAlaThrAlaGluLysValPheLysGlnTyrAlaAsnAspAsnGlyValGluGlyGluTrpAlaTyrAspAspAlaThrLysThrPheAbuValThrGlu-NH₂ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 13192 - 13193

13
H-cysteine(trityl)-2-chlorotrityl resin [ No CAS ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 71989-31-6 ]
[ 35661-40-6 ]
[ 71989-33-8 ]
[ 104091-09-0 ]
[ 71989-14-5 ]
[ 71989-35-0 ]
[ 132388-59-1 ]
[ 67436-13-9 ]
[ 119831-72-0 ]
FFC(Acm)PFGC(t-Bu)ALVDCGPNRPC(t-Bu)RDTGFESC(Acm)DC [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2013,vol. 11,p. 1476 - 1481

14
[ 946849-80-5 ]
[ 112883-29-1 ]
[ 22204-53-1 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 115057-37-9 ]
[ 175281-76-2 ]
C₇₉H₉₄N₁₀O₂₅S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: The compounds were synthesized by solid phase peptide synthesis (SPPS) using 2-chlorotrityl chloride resin. The corresponding N-Fmoc protected amino acids with side chains properly protected, Fmoc-succinated cystamine, and <strong>[175281-76-2]4-(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy)butanoic acid</strong> were used for SPPS. The first amino acidwas loaded on the resin at the C-terminal with the loading efficiency about 0.6 mmol/g. 20% piperidine in anhydrous N,N-dimethylformamide (DMF) was used during deprotection of Fmoc group. The next Fmoc-protected amino acid (3 equiv.) was then coupled to the free amino group using O-(Benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate (HBTU, 1 equiv.to Fmoc-AA) as the coupling reagent. The growth of the peptide chain was according to the established Fmoc SPPS protocol. After the last coupling step, excessive reagents were removed by a single DMF wash for 5minutes (5 mL per gram of resin), followed by five steps of washing using DCM for 1 min (5 mL per gram of resin). The peptide derivative was cleaved using 92.5% of trifluoroacetic acid with 2.5% of TMS, 2.5% of phenol,and 2.5% of H2O for 20 minutes. 20 mL per gram of resin of ice-cold diethylether was then added to cleavage reagent. The resulting precipitate was filtrated and washed by ice-cold diethylether. The resulting solid was purified by HPLC and dried by lyophilizer.

Reference： [1]Journal of Nanoscience and Nanotechnology,2014,vol. 14,p. 4837 - 4842

15
[ 112883-29-1 ]
[ 22204-53-1 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 115057-37-9 ]
[ 175281-76-2 ]
C₆₁H₆₆N₆O₁₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: The compounds were synthesized by solid phase peptide synthesis (SPPS) using 2-chlorotrityl chloride resin. The corresponding N-Fmoc protected amino acids with side chains properly protected, Fmoc-succinated cystamine, and <strong>[175281-76-2]4-(4-(1-hydroxyethyl)-2-methoxy-5-nitrophenoxy)butanoic acid</strong> were used for SPPS. The first amino acidwas loaded on the resin at the C-terminal with the loading efficiency about 0.6 mmol/g. 20% piperidine in anhydrous N,N-dimethylformamide (DMF) was used during deprotection of Fmoc group. The next Fmoc-protected amino acid (3 equiv.) was then coupled to the free amino group using O-(Benzotriazol-1-yl)-N,N,N,N-tetramethyluroniumhexafluorophosphate (HBTU, 1 equiv.to Fmoc-AA) as the coupling reagent. The growth of the peptide chain was according to the established Fmoc SPPS protocol. After the last coupling step, excessive reagents were removed by a single DMF wash for 5minutes (5 mL per gram of resin), followed by five steps of washing using DCM for 1 min (5 mL per gram of resin). The peptide derivative was cleaved using 92.5% of trifluoroacetic acid with 2.5% of TMS, 2.5% of phenol,and 2.5% of H2O for 20 minutes. 20 mL per gram of resin of ice-cold diethylether was then added to cleavage reagent. The resulting precipitate was filtrated and washed by ice-cold diethylether. The resulting solid was purified by HPLC and dried by lyophilizer.

Reference： [1]Journal of Nanoscience and Nanotechnology,2014,vol. 14,p. 4837 - 4842

16
[ 68858-20-8 ]
[ 35661-39-3 ]
[ 104091-09-0 ]
[ 132388-59-1 ]
[ 71989-20-3 ]
[ 91000-69-0 ]
[ 135112-28-6 ]
C₃₇H₆₅N₁₃O₁₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 9396 - 9408

17
[ 949026-86-2 ]
[ 35661-39-3 ]
C₁₂H₁₆N₂O₃ [ No CAS ]
[ 104091-09-0 ]
[ 132388-59-1 ]
[ 91000-69-0 ]
[ 135112-28-6 ]
C₅₂H₇₇N₁₇O₁₇ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 9396 - 9408

18
[ 949026-86-2 ]
[ 35661-39-3 ]
C₁₂H₁₆N₂O₃ [ No CAS ]
[ 104091-09-0 ]
[ 73724-45-5 ]
[ 91000-69-0 ]
[ 135112-28-6 ]
C₃₇H₆₅N₁₃O₁₂ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 9396 - 9408

19
[ 334-48-5 ]
[ 29022-11-5 ]
C₂₃H₂₀N₄O₃ [ No CAS ]
[ 104091-09-0 ]
[ 35661-38-2 ]
[ 73731-37-0 ]
[ 73724-45-5 ]
[ 109425-55-0 ]
[ 88223-98-7 ]
[ 144120-53-6 ]
[ 144120-52-5 ]
[ 143824-78-6 ]
[ 333366-23-7 ]
(S)-2-azido-3-(1-(tert-butoxycarbonyl)-1H-indol-3-yl)propanoic acid [ No CAS ]
Dap-E₁₂-W₁₃ [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 748 - 751

20
[ 334-48-5 ]
[ 29022-11-5 ]
C₂₃H₂₀N₄O₃ [ No CAS ]
[ 104091-09-0 ]
[ 71989-38-3 ]
[ 35661-38-2 ]
[ 73731-37-0 ]
[ 73724-45-5 ]
[ 109425-55-0 ]
[ 88223-98-7 ]
[ 144120-53-6 ]
[ 144120-52-5 ]
[ 333366-23-7 ]
(S)-2-azido-3-(1-(tert-butoxycarbonyl)-1H-indol-3-yl)propanoic acid [ No CAS ]
C₇₀H₉₈N₁₆O₂₆ [ No CAS ]

Reference： [1]Organic Letters,2015,vol. 17,p. 748 - 751

21
H-Ala-2-chlorotrityl resin [ No CAS ]
[ 504-99-4 ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 118904-37-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 73724-45-5 ]
[ 73724-45-5 ]
[ 35737-15-6 ]
[ 161420-87-7 ]
Fmoc-D-Dab(NH2)-OH [ No CAS ]
tridecaptin B₁ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 6073 - 6081

22
H-Ala-2-chlorotrityl resin [ No CAS ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 118904-37-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 73724-45-5 ]
[ 73724-45-5 ]
[ 35737-15-6 ]
[ 161420-87-7 ]
(R)-6-methyloctanoic acid [ No CAS ]
Fmoc-D-Dab(NH2)-OH [ No CAS ]
(6′R)-methyloctanoyl tridecaptin B1 [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 6073 - 6081

23
H-Ala-2-chlorotrityl resin [ No CAS ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 118904-37-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 73724-45-5 ]
[ 73724-45-5 ]
[ 35737-15-6 ]
[ 161420-87-7 ]
Fmoc-D-Dab(NH2)-OH [ No CAS ]
C₅₈H₉₅N₁₇O₁₈ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 6073 - 6081

24
H-Ala-2-chlorotrityl resin [ No CAS ]
[ 124-07-2 ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 118904-37-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 73724-45-5 ]
[ 73724-45-5 ]
[ 35737-15-6 ]
[ 161420-87-7 ]
Fmoc-D-Dab(NH2)-OH [ No CAS ]
C₆₆H₁₀₉N₁₇O₁₉ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 6073 - 6081

25
[ 7423-55-4 ]
[ 68858-20-8 ]
[ 71989-31-6 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 108-24-7 ]
[ 71989-16-7 ]
[ 159857-60-0 ]
Ac-Phe-Glu-Asp-Asn-Phe-Val-Pro-Lys(3-maleimidopropionyl)-NH₂ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 8008 - 8015

26
[ 7423-55-4 ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 108-24-7 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 159857-60-0 ]
Ac-Lys-Gly-Trp-Val-Thr-Phe-Glu-Glu-Lys(3-maleimidopropionyl)-NH₂ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 8008 - 8015

27
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 73731-37-0 ]
[ 105047-45-8 ]
[ 76-05-1 ]
[ 138775-22-1 ]
[ 158599-00-9 ]
Boc-Orn(Fmoc)-OH [ No CAS ]
C₉₃H₁₄₇IN₂₀O₂₁*2C₂HF₃O₂ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 6304 - 6311

28
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 73731-37-0 ]
[ 105047-45-8 ]
[ 76-05-1 ]
[ 138775-22-1 ]
[ 158599-00-9 ]
Boc-Orn(Fmoc)-OH [ No CAS ]
C₉₅H₁₅₁IN₂₀O₂₃*2C₂HF₃O₂ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 6304 - 6311

29
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 73731-37-0 ]
[ 105047-45-8 ]
[ 103478-58-6 ]
[ 76-05-1 ]
[ 158599-00-9 ]
Boc-Orn(Fmoc)-OH [ No CAS ]
C₉₂H₁₄₅IN₂₀O₂₁*2C₂HF₃O₂ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 6304 - 6311

30
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 73731-37-0 ]
[ 105047-45-8 ]
[ 103478-58-6 ]
[ 76-05-1 ]
[ 158599-00-9 ]
Boc-Orn(Fmoc)-OH [ No CAS ]
C₉₄H₁₄₉IN₂₀O₂₃*2C₂HF₃O₂ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2015,vol. 137,p. 6304 - 6311

31
[ 404858-60-2 ]
Paramax Wang resin [ No CAS ]
[ 64987-85-5 ]
[ 29022-11-5 ]
[ 104091-09-0 ]
[ 88574-06-5 ]
C₄₄H₆₄N₈O₂₂S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Synthesis of Compound 1 (ZJ-MCC-Ahx-dEdEdEG): The peptide Fmoc-Ahx-dGlu-dGlu-dGlu-G was assembled on a Wang resin. The three glutamates (dGlu) are of D-isoform. Peptide synthesis was carried out manually by Fmoc chemistry with HCTU (2-(6-Chloro-1H-benzotriazole-1-yl)-1,1,3,3-tetramethylaminium hexafluorophosphate) activation. Generally, peptides were synthesized at a 0.01 mmol scale starting from the C-terminal amino acid on solid support. Fmoc-deprotection at each cycle was carried out using 20percent piperidine in DMF. Coupling reactions were carried out using 3.3 eq. of Fmoc-amino acids in DMF activated with 3.3 eq. of HCTU and 5 equivalents of diisopropylethylamine (DIPEA) in DMF. These steps were repeated each time with an amino acid added. After the peptide sequence was built on the resin, the Fmoc group of the N-terminal amino acid was deprotected. Coupling of 4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) to the N-terminal amine group was achieved with 3.3 equivalents of SMCC in DMF. Coupling of Cys-C(O)-Glu was performed using 3.3 equivalents of Cys-C(O)-Glu in DMF after coupling SMCC to the peptide. The final peptide resin was washed with DMF and then dichloromethane and dried. Cleavage and deprotection were carried out using TFA/water/triisopropylsilane (950:25:25) for 1 h, the resin was removed by filtration and washed with TFA. The combined filtrate was dried under nitrogen. The synthesized peptide was precipitated by the addition of diethyl ether and collected by centrifugation. The cleaved peptide was purified by preparative HPLC. The products were ascertained by high resolution matrix-assisted laser desorption/ionization mass (MALDI-MS) spectra. Then Fmoc was deprotected followed by coupling of SMCC and Cys-C(O)-Glu. The product has retention time of 11.9 minutes on analytical HPLC with 0-55percent gradient over 45 minutes (flow rate 1 ml/min; A: 10 mM triethylammonium acetate TEAA, pH 7.0; B was acetonitrile.) The mass was verified by MALDI/TOF mass spectrometry?Calculated: 1088.4 (C44H64N8O22S). Found m/z: 1089.4 (M+1).

Reference： [1]Patent: US2015/209453,2015,A1 .Location in patent: Paragraph 0084

32
[ 112898-00-7 ]
[ 168300-88-7 ]
[ 29022-11-5 ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 73724-45-5 ]
[ 86123-10-6 ]
[ 71989-28-1 ]
[ 110990-08-4 ]
[ 104091-09-0 ]
[ 71989-31-6 ]
[ 84624-17-9 ]
[ 157355-81-2 ]
N-Fmoc-tyrosine [ No CAS ]
N-9-fluorenylmethoxycarbonyl-D-aspartic acid [ No CAS ]
Fmoc-D-Asn-OH [ No CAS ]
Fmoc-D-Ile-OH [ No CAS ]
D-(Ala-Phe-Thr-Val-Thr-Val-Pro-Lys-Asp-Leu-Tyr-Val-Val-Glu-Tyr-Gly-Ser-Asn-Met-Thr-Ile-Glu-(S-((acetamido)methyl)Cys)-Lys-Phe-Pro-Val-Glu-Lys-Gln-Leu-Asp-Leu-Ala)-NHNH2 [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2015,vol. 54,p. 11760 - 11764
Angew. Chem.,2015,vol. 127,p. 11926 - 11930,5

33
[ 112898-00-7 ]
[ 29022-11-5 ]
[ 35737-15-6 ]
[ 35661-60-0 ]
[ 73724-45-5 ]
[ 86123-10-6 ]
[ 71989-28-1 ]
[ 110990-08-4 ]
[ 104091-09-0 ]
[ 84624-17-9 ]
[ 157355-79-8 ]
N-Fmoc-tyrosine [ No CAS ]
N-9-fluorenylmethoxycarbonyl-D-aspartic acid [ No CAS ]
[ 157355-80-1 ]
Fmoc-D-Asn-OH [ No CAS ]
Fmoc-D-arginine [ No CAS ]
Fmoc-D-Ile-OH [ No CAS ]
D-(Cys-Leu-Ile-Val-Tyr-Trp-Glu-Met-Glu-Asp-Lys-Asn-Ile-Ile-Gln-Phe-Val-His-Gly-Glu-Glu-Asp-Leu-Lys-Val-Gln-His-Ser-Ser-Tyr-Arg-Gln-Arg)-NHNH2 [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2015,vol. 54,p. 11760 - 11764
Angew. Chem.,2015,vol. 127,p. 11926 - 11930,5

34
[ 112898-00-7 ]
Fmoc-Val-Wang resin [ No CAS ]
C₂₀H₃₀N₂O₁₂S [ No CAS ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 73731-37-0 ]
[ 500533-95-9 ]
[ 110990-08-4 ]
[ 76-05-1 ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
(x)C₂HF₃O₂*C₁₃₆H₂₁₉N₄₁O₄₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: Peptides (e.g. IETDV (SEQ ID NO: 18) or IETAV (SEQ ID NO: 16)) were synthesized by Fmoc-based solid phase peptide chemistry using preloaded Fmoc-Val-Wang-resin (0.6-0-7 mmol/g, 100-200 mesh), HBTU/DIPEA for couplings, and dry DMF as solvent. Each coupling was carried out for 40 min with a 1/4/3.9/8 stoichiometry of resin/Fmoc-amino acid/HBTU/DIPEA, and was qualitatively evaluated by the ninhydrin test. Fmoc-deprotection was carried out in 20% piperidine in DMF for 5 min, followed by DMF wash and a second piperidine/DMF treatment for 15 min. 1.3 Synthesis of NPEG4-based Dimeric Ligands AB141, AB144 and AB147 (FIGS. 2 and 3) (0147) Ns-NPEG4-diacid-linkerA (3, Scheme 1; 0.1 eq., 0.025 mmol) was pre-activated with HBTU (0.2 eq, 0.05 mmol) and DIPEA (0.4 eq, 0.1 mmol) and added to Fmoc-deprotected Wang-resin-bound IETDV (SEQ ID NO: 18) (1 eq, 0.25 mmol) in a total volume of 4 mL DMF. The reaction was shaken for 45 min and repeated 5 times. The Ns group was removed by adding DBU (0.5 mmol) in DMF (2 mL) followed by mercaptoethanol (0.5 mmol) in DMF (2 mL). The reaction was shaken for 30 min and washed in DMF. Treatment with mercaptoethanol/DBU was repeated once, and the resin washed consecutively with DMF, DCM, MeOH and DCM to provide resin-bound AB141. For AB144 and AB147 the first amino acid of the CPP (L- or D-Arg, respectively) was coupled to the nitrogen by six consecutive couplings of Fmoc-Arg(Pbf)-OH. For each coupling, Fmoc-Arg(Pbf)-OH (0.5 mmol) was activated by HATU in DMF (2 mL, 0.244 M) and collidine (132 muL), before adding it to the drained resin. After 40 minutes of shaking and a DMF wash, the coupling and DMF wash was repeated 5 times followed by a thorough DMF wash. Fmoc was removed with 20% piperidine in DMF, the remaining Tat- or Retroinverso-D-Tat sequence synthesized as described for peptide synthesis, and the final Fmoc group removed.Fluorescent ligands were prepared by coupling 5-FAM(5-carboxyfluorescein; Anaspec, San Jose, Calif., USA) tothe N-terminal amino group of the final and Fmoc-deprotected AB144, AB147, or Tat-NR2B9c, while bound to theresin, to produce AB145, AB148, and M523, respectively.Likewise, 5-FAM was coupled to Ns-deprotected, resin-bound AB141 to produce AB143. 5-FAM was coupled in a1/2/2/3 ratio of N-sites-resin5-FAMJHATIJ/collidine in atotal of 2 mL DMF at a 0.07 mmol scale (molar of NPEGlinker). For AB145, AB148, or M523, coupling time was 6hours. For AB143, 5-FAM was coupled by two consecutivecouplings of 6 and 16 hours, respectively.Synthesized compounds, including dimeric PSD-95 inhibitors and derivatives thereof, were obtained as TFA saltsby treating the resin-bound products with trifluoroacetic acid (TFA)/triisopropylsilane/H20 (90/5/5) for 2 hours (unless other specification is stated), evaporation in vacuo, precipitation with cold ether, lyophilization, and purification with preparative reverse phase high-performance liquid chromatography (RP-HPLC). Compounds were characterized byanalytical HPLC and mass spectrometry (Table 1).

Reference： [1]Patent: US9139615,2015,B2 .Location in patent: Page/Page column 20; 21; 22

35
[ 112898-00-7 ]
Fmoc-Val-Wang resin [ No CAS ]
C₂₀H₃₀N₂O₁₂S [ No CAS ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 73731-37-0 ]
[ 110990-08-4 ]
[ 76-05-1 ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
(x)C₂HF₃O₂*C₁₁₅H₂₀₉N₄₁O₃₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Peptides (e.g. IETDV (SEQ ID NO: 18) or IETAV (SEQ ID NO: 16)) were synthesized by Fmoc-based solid phase peptide chemistry using preloaded Fmoc-Val-Wang-resin (0.6-0-7 mmol/g, 100-200 mesh), HBTU/DIPEA for couplings, and dry DMF as solvent. Each coupling was carried out for 40 min with a 1/4/3.9/8 stoichiometry of resin/Fmoc-amino acid/HBTU/DIPEA, and was qualitatively evaluated by the ninhydrin test. Fmoc-deprotection was carried out in 20% piperidine in DMF for 5 min, followed by DMF wash and a second piperidine/DMF treatment for 15 min. 1.3 Synthesis of NPEG4-based Dimeric Ligands AB141, AB144 and AB147 (FIGS. 2 and 3) (0147) Ns-NPEG4-diacid-linkerA (3, Scheme 1; 0.1 eq., 0.025 mmol) was pre-activated with HBTU (0.2 eq, 0.05 mmol) and DIPEA (0.4 eq, 0.1 mmol) and added to Fmoc-deprotected Wang-resin-bound IETDV (SEQ ID NO: 18) (1 eq, 0.25 mmol) in a total volume of 4 mL DMF. The reaction was shaken for 45 min and repeated 5 times. The Ns group was removed by adding DBU (0.5 mmol) in DMF (2 mL) followed by mercaptoethanol (0.5 mmol) in DMF (2 mL). The reaction was shaken for 30 min and washed in DMF. Treatment with mercaptoethanol/DBU was repeated once, and the resin washed consecutively with DMF, DCM, MeOH and DCM to provide resin-bound AB141. For AB144 and AB147 the first amino acid of the CPP (L- or D-Arg, respectively) was coupled to the nitrogen by six consecutive couplings of Fmoc-Arg(Pbf)-OH. For each coupling, Fmoc-Arg(Pbf)-OH (0.5 mmol) was activated by HATU in DMF (2 mL, 0.244 M) and collidine (132 muL), before adding it to the drained resin. After 40 minutes of shaking and a DMF wash, the coupling and DMF wash was repeated 5 times followed by a thorough DMF wash. Fmoc was removed with 20% piperidine in DMF, the remaining Tat- or Retroinverso-D-Tat sequence synthesized as described for peptide synthesis, and the final Fmoc group removed.Synthesized compounds, including dimeric PSD-95 inhibitors and derivatives thereof, were obtained as TFA saltsby treating the resin-bound products with trifluoroacetic acid (TFA)/triisopropylsilane/H20 (90/5/5) for 2 hours (unless other specification is stated), evaporation in vacuo, precipitation with cold ether, lyophilization, and purification with preparative reverse phase high-performance liquid chromatography (RP-HPLC). Compounds were characterized byanalytical HPLC and mass spectrometry (Table 1).

Reference： [1]Patent: US9139615,2015,B2 .Location in patent: Page/Page column 20; 21; 22

36
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 108-24-7 ]
[ 35737-15-6 ]
[ 71989-28-1 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 71989-20-3 ]
[ 204777-78-6 ]
(S)-6-[(Diphenyl-p-tolyl-methyl)-amino]-2-(9H-fluoren-9-ylmethoxycarbonylamino)-hexanoic acid [ No CAS ]
Ac-Ala-Met-Val-Ser-Glu-Phe-Leu-(Ac-(Lys-Ac)Lys-Lys)Lys-Gln-Ala-Trp-NH₂ [ No CAS ]

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.

Reference： [1]Patent: WO2015/162485,2015,A1 .Location in patent: Page/Page column 59; 63; 64

37
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 71989-20-3 ]
[ 91000-69-0 ]
[ 96402-49-2 ]
[ 94744-50-0 ]
Y-(α-aminoisobutyroyl)-EGTFTSDYSIYLDKKAQRAFVNWLLA-(α-aminoisobutyroyl)-KYG-(β-(1-naphthyl)-alaninoyl)-LDF-NH2 [ No CAS ]

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

Reference： [1]Patent: US2015/299281,2015,A1 .Location in patent: Paragraph 0147-0155

38
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 71989-20-3 ]
[ 77128-73-5 ]
[ 91000-69-0 ]
[ 116611-64-4 ]
C₁₅₀H₂₂₈N₄₀O₄₅ [ No CAS ]

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.

Reference： [1]Bioorganic and Medicinal Chemistry,2016,vol. 24,p. 1163 - 1170

39
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 198561-07-8 ]
[ 684270-46-0 ]
C₅₈H₉₀N₂₀O₁₈ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2016,vol. 22,p. 5534 - 5537

40
[ 942518-20-9 ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 198561-07-8 ]
C₅₉H₉₂N₂₀O₁₈ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2016,vol. 22,p. 5534 - 5537

41
[ 1097192-04-5 ]
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 198561-07-8 ]
C₆₀H₉₄N₂₀O₁₈ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2016,vol. 22,p. 5534 - 5537

42
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 23235-01-0 ]
[ 71989-31-6 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 71989-20-3 ]
[ 91000-69-0 ]
[ 77284-32-3 ]
[ 159610-92-1 ]
(norleucine)LSDEDFKAVFG(norleucine)TRSAFANLPLWKQ(glycine-2-propargyl)NLK((2S)‐2‐amino‐6‐azidohexanoic acid)EKGLF [ No CAS ]
(norleucine)LSDEDFKAVFG(norleucine)TRSAFANLPLWKQDNLKKEKGLF [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 5768 - 5773

43
[ 29022-11-5 ]
[ 68858-20-8 ]
C₂₄H₂₃NO₅ [ No CAS ]
[ 71989-31-6 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 135112-27-5 ]
GEWAYNPATGKF(Abu)VTE [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 3902 - 3905

44
[ 29022-11-5 ]
[ 68858-20-8 ]
C₂₄H₂₃NO₅ [ No CAS ]
[ 71989-31-6 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
[ 35737-15-6 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 135112-28-6 ]
GEWAYNPATGKF(Nva)VTE [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 3902 - 3905

45
[ 68858-20-8 ]
C₂₃H₂₁N₅O₇ [ No CAS ]
Fmoc-Peg-fluoresceinamide [ No CAS ]
[ 104091-09-0 ]
[ 71989-38-3 ]
[ 150009-58-8 ]
[ 166108-71-0 ]
C₈₀H₉₁N₁₃O₃₀ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 153 - 157
Angew. Chem.,2017,vol. 129,p. 159 - 163,5

46
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 108-24-7 ]
[ 71989-38-3 ]
[ 150009-58-8 ]
AcGDEVDGYGY-NH2 [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 153 - 157
Angew. Chem.,2017,vol. 129,p. 159 - 163,5

47
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 108-24-7 ]
[ 71989-38-3 ]
[ 150009-58-8 ]
C₄₄H₅₈N₁₀O₁₈ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 153 - 157
Angew. Chem.,2017,vol. 129,p. 159 - 163,5

48
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 108-24-7 ]
[ 71989-38-3 ]
[ 150009-58-8 ]
C₄₄H₅₈N₁₀O₁₈ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 153 - 157
Angew. Chem.,2017,vol. 129,p. 159 - 163,5

49
[ 29022-11-5 ]
[ 68858-20-8 ]
[ 104091-09-0 ]
[ 108-24-7 ]
[ 71989-38-3 ]
[ 150009-58-8 ]
C₄₆H₆₀N₁₀O₂₀ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 153 - 157
Angew. Chem.,2017,vol. 129,p. 159 - 163,5

50
[ 29022-11-5 ]
[ 68858-20-8 ]
C₂₃H₂₁N₅O₇ [ No CAS ]
Fmoc-Gly-5-aminofluorescein [ No CAS ]
[ 104091-09-0 ]
[ 71989-38-3 ]
[ 150009-58-8 ]
C₈₀H₈₇N₁₇O₃₀ [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 153 - 157
Angew. Chem.,2017,vol. 129,p. 159 - 163,5

51
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 71195-85-2 ]
[ 35661-40-6 ]
[ 104091-09-0 ]
acryloyl-Phe-Leu-Ala-Phe-Glu [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 728 - 732
Angew. Chem.,2017,vol. 129,p. 746 - 750,5

52
[ 24156-53-4 ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
C₁₈H₁₇NO₃ [ No CAS ]
[ 104091-09-0 ]
[ 204777-78-6 ]
Fmoc-Asp(pg)-OH [ No CAS ]
Fmoc-Gln(pg)-OH [ No CAS ]
Fmoc-Ser(pg)-OH [ No CAS ]
Fmoc-Arg(pg)-OH [ No CAS ]
Fmoc-Thr(pg)-OH [ No CAS ]
C₈₅H₁₄₇N₃₃O₃₁ [ No CAS ]

Reference： [1]Australian Journal of Chemistry,2017,vol. 70,p. 184 - 190

53
[ 867062-95-1 ]
C₃₂H₂₈NO₅Pol [ No CAS ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 71989-31-6 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 91000-69-0 ]
[ 116783-35-8 ]
[ 116611-64-4 ]
C₁₅₃H₂₃₂N₄₀O₄₃ [ No CAS ]

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.

Reference： [1]Synlett,2017,vol. 28,p. 1961 - 1965

54
[ 867062-95-1 ]
C₃₂H₂₈NO₅Pol [ No CAS ]
[ 68858-20-8 ]
[ 35661-60-0 ]
[ 35661-39-3 ]
[ 112883-29-1 ]
[ 71989-31-6 ]
[ 35661-40-6 ]
[ 136083-57-3 ]
[ 104091-09-0 ]
[ 73731-37-0 ]
[ 71989-16-7 ]
[ 105047-45-8 ]
[ 73724-45-5 ]
[ 91000-69-0 ]
[ 116611-64-4 ]
C₁₅₃H₂₃₂N₄₀O₄₃ [ No CAS ]

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.

Reference： [1]Synlett,2017,vol. 28,p. 1961 - 1965

55
[ 198545-76-5 ]
[ 29022-11-5 ]
C₉H₁₀N₃O₃Pol [ No CAS ]
[ 35661-38-2 ]
[ 35661-60-0 ]
[ 71989-33-8 ]
[ 94744-50-0 ]
[ 104091-09-0 ]
[ 84624-17-9 ]
Fmoc-D-Tyr(O-tBu)-OH [ No CAS ]
1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan [ No CAS ]
N-9-fluorenylmethoxycarbonyl-D-aspartic acid [ No CAS ]
(R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-N-trityl-succinamic acid [ No CAS ]
N-α-[(9H-fluoren-9-ylmethoxy)carbonyl]-N^G-(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)-D-arginine [ No CAS ]
C₈₀H₁₂₀BrN₂₃O₂₆ [ No CAS ]