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Chemical Structure| 15761-38-3 Chemical Structure| 15761-38-3
Chemical Structure| 15761-38-3

*Storage: Keep in dark place,Inert atmosphere,Room temperature.

Boc-Ala-OH

CAS No.: 15761-38-3

Synonyms: Boc-L-Ala-OH;Boc-Ala-OH

4.5 *For Research Use Only !

Cat. No.: A142030 Purity: 97%

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Product Details of [ 15761-38-3 ]

CAS No. :15761-38-3
Formula : C8H15NO4
Linear Structure Formula :COOHCHCH3NHCOOC(CH3)3
M.W : 189.21
SMILES Code : C[C@H](NC(OC(C)(C)C)=O)C(O)=O
Synonyms :
Boc-L-Ala-OH;Boc-Ala-OH
MDL No. :MFCD00037225
InChI Key :QVHJQCGUWFKTSE-YFKPBYRVSA-N
Pubchem ID :85082

Safety of [ 15761-38-3 ]

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

Calculated chemistry of [ 15761-38-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 13
Num. arom. heavy atoms 0
Fraction Csp3 0.75
Num. rotatable bonds 5
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 46.86
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

75.63 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.79
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

0.92
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

0.98
Log Po/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.

0.51
Log Po/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

-0.17
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.81

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-1.26
Solubility 10.3 mg/ml ; 0.0546 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.09
Solubility 1.52 mg/ml ; 0.00805 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

-0.64
Solubility 43.0 mg/ml ; 0.228 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

No
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

No
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

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.8 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

1.0
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<1.0
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)

2.54

Application In Synthesis [ 15761-38-3 ]

* 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 [ 15761-38-3 ]

[ 15761-38-3 ] Synthesis Path-Downstream   1~24

  • 1
  • [ 15761-38-3 ]
  • [ 146844-02-2 ]
  • [ 59524-70-8 ]
  • 2
  • [ 15761-38-3 ]
  • [ 40350-83-2 ]
  • (±)-1-azafagomine [ No CAS ]
  • [ 541-88-8 ]
  • (2S,4R)-1-{(2S,4R)-1-[2-(4,5-Dihydroxy-3-hydroxymethyl-tetrahydro-pyridazin-1-yl)-acetyl]-4-hydroxy-pyrrolidine-2-carbonyl}-4-hydroxy-pyrrolidine-2-carboxylic acid ((S)-1-carbamoyl-ethyl)-amide [ No CAS ]
  • 3
  • [ 506-68-3 ]
  • [ 15761-38-3 ]
  • [ 3262-72-4 ]
  • [ 53308-95-5 ]
  • 4-methylbenzhydrylamine resin [ No CAS ]
  • (R)-2-((S)-2-Imino-4-methyl-imidazolidin-1-yl)-3-((S)-2-imino-5-propyl-imidazolidin-1-yl)-propan-1-ol [ No CAS ]
  • 4
  • [ 15761-38-3 ]
  • [ 1479-58-9 ]
  • (S)-{1-[4-bromo-2-(2-fluoro-benzoyl)-phenylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester [ No CAS ]
  • [ 2387-23-7 ]
YieldReaction ConditionsOperation in experiment
79% With dicyclohexyl-carbodiimide; In dichloromethane; at 0 - 20℃; for 8.5h; {1-[4-Bromo-2-(2-fluoro-benzoyl)-phenylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester 116.; To a stirred solution of <strong>[1479-58-9](2-amino-5-bromophenyl)-(2-fluoro-phenyl)-methanone</strong> (60 g, 204 mmol) 115 and the N-Boc-L-alanine 107 (38.59 g, 204 mmol) in CH2Cl2 (500 mL) was added dicyclohexylcarbodiimide (DCC) (42.09 g, 204 mmol) in CH2Cl2 (200 mL) dropwise, over a 30 min period at 0° C. The reaction mixture was allowed to stir an additional 8 h at rt. The dicyclohexyl urea which formed was filtered off and the filtrate concentrated under reduced pressure. The crude solid residue 116 was purified by recrystallization from hexane and EtOAc to afford 116 (74.9 g, 79percent). mp 158-159° C.; IR (KBr, cm-1) 3332, 2931, 255, 1694, 1643, 1613, 1582, 1537, 1450; 1H NMR (CDCl3) delta 11.68 (s, 1H), 8.71 (d, J=9.0 Hz, 1H), 7.69 (dd, J=9.0, 2.3 Hz, 1H), 7.55-7.62 (m, 2H), 7.46 (td, J=7.6, 1.4 Hz, 1H), 7.30 (t, J=7.5 Hz, 1H), 7.21 (t, J=9.1 Hz, 1H), 5.13 (b, 1H), 4.37 (b, 1H), 1.51 (d, J=7.2 Hz, 3H), 1.45 (S, 9H). MS (EI) m/e (relative intensity) 467 (M++2, 14), 466 (M++1, 44), 465 (M+, 14), 464 (42), 329 (15), 321 (60), 295 (100), 224 (26); [alpha]26D=-59.1 (c 0.51, EtOAc).
  • 5
  • [ 15761-38-3 ]
  • [ 124-41-4 ]
  • [ 3034-48-8 ]
  • [ 88374-44-1 ]
  • 7
  • [ 112392-66-2 ]
  • [ 15761-38-3 ]
  • [ 91103-47-8 ]
YieldReaction ConditionsOperation in experiment
With lyophilized cells of Bacillus amyloliquefaciens WZZ002; In aq. phosphate buffer; at 35℃; for 10h;pH 8.0;Enzymatic reaction;Kinetics; Enantioselective hydrolysis was performed on Boc-dl-Ala-OMe by adding both a substrate with a concentration range of 0.1 to 4.0M and a 500mg lyophilized cell of B. amyloliquefaciens WZZ002 in a 10mL (50mL flask) phosphate buffer solution (0.2M, pH6.0-12.0) at 20C to 60C. The solution was stirred at 400rpm. The pH level was controlled through automatic titration using different alkali solutions (2M). The samples were withdrawn at regular intervals and were immediately acidified with HCl (2M) to stop the reaction and to enhance the extractability of Boc-dl-Ala. The sample was extracted using ethyl acetate, whereas the organic phase was isolated and dried using anhydrous Na2SO4 for gas chromatography (GC) analysis. All experiments were conducted in triplicate, unless specified. The time course of enantioselective hydrolysis reaction was performed by adding 2M of Boc-dl-Ala-OMe and 5g of the lyophilized cell of B. amyloliquefaciens WZZ002 in 100mL (250mL flask) phosphate buffer solution (0.2M, pH8.0). The pH of the reaction was controlled through automatic titration using 6M of NH3·H2O to reduce the increasing amount of the neutralizer.
  • 8
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 19746-37-3 ]
  • [ 13836-37-8 ]
  • C25H38N3O6PolS [ No CAS ]
  • [ 47689-67-8 ]
  • [ 170384-29-9 ]
  • C78H108BrN16O21PolS3 [ No CAS ]
  • 9
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 13836-37-8 ]
  • C25H38N3O6PolS [ No CAS ]
  • [ 61925-77-7 ]
  • [ 47689-67-8 ]
  • [ 170384-29-9 ]
  • C82H109BrN15O20PolS3 [ No CAS ]
  • 10
  • polyethylene glycol polyamide resin [ No CAS ]
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 13139-16-7 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 23680-31-1 ]
  • [ 61925-77-7 ]
  • [ 73821-97-3 ]
  • [ 47689-67-8 ]
  • [ 83468-83-1 ]
  • [ 65420-40-8 ]
  • [ 170384-29-9 ]
  • H-CSCRLYELLHGAGNHAAGILTL-NH2 [ No CAS ]
  • 11
  • [ 15761-38-3 ]
  • [ 7536-58-5 ]
  • [ 13726-85-7 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 40350-83-2 ]
  • RDCCTOOKKCKDKQCKOQRCCA-NH2, containing three disulfide bonds between Cys<SUP>3</SUP> and Cys<SUP>15</SUP>, Cys<SUP>4</SUP> and Cys<SUP>20</SUP>, Cys<SUP>10</SUP> and Cys<SUP>21</SUP>, O: 4-trans-hydroxyproline<SUP> </SUP> [ No CAS ]
  • 12
  • [ 15761-38-3 ]
  • [ 7536-58-5 ]
  • [ 13726-85-7 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 40350-83-2 ]
  • RDCCTOOKKCKDRQCKOQKCCA-NH2, containing three disulfide bonds between Cys<SUP>3</SUP> and Cys<SUP>15</SUP>, Cys<SUP>4</SUP> and Cys<SUP>20</SUP>, Cys<SUP>10</SUP> and Cys<SUP>21</SUP>, O: 4-trans-hydroxyproline [ No CAS ]
  • 13
  • [ 15761-38-3 ]
  • [ 7536-58-5 ]
  • [ 13726-85-7 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 40350-83-2 ]
  • KDCCTOOKKCKDKQCKOQRCCA-NH2, containing three disulfide bonds between Cys<SUP>3</SUP> and Cys<SUP>15</SUP>, Cys<SUP>4</SUP> and Cys<SUP>20</SUP>, Cys<SUP>10</SUP> and Cys<SUP>21</SUP>, O: 4-trans-hydroxyproline [ No CAS ]
  • 14
  • [ 15761-38-3 ]
  • [ 7536-58-5 ]
  • [ 13726-85-7 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 40350-83-2 ]
  • KDCCTOOKKCKDRQCKOQKCCA-NH2, containing three disulfide bonds between Cys<SUP>3</SUP> and Cys<SUP>15</SUP>, Cys<SUP>4</SUP> and Cys<SUP>20</SUP>, Cys<SUP>10</SUP> and Cys<SUP>21</SUP>, O: 4-trans-hydroxyproline [ No CAS ]
  • 15
  • [ 15761-38-3 ]
  • [ 7536-58-5 ]
  • [ 13726-85-7 ]
  • [ 15260-10-3 ]
  • [ 13836-37-8 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 40350-83-2 ]
  • KDCCTOOKKCKDRQCKOQRCCA-NH2, O: 4-trans-hydroxyproline [ No CAS ]
  • 16
  • [ 15761-38-3 ]
  • [ 7536-58-5 ]
  • [ 13726-85-7 ]
  • [ 15260-10-3 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 40350-83-2 ]
  • RDCCTOOKKCKDKQCKOQKCCA-NH2, O: 4-trans-hydroxyproline [ No CAS ]
  • 17
  • [ 15761-38-3 ]
  • [ 7536-58-5 ]
  • [ 13726-85-7 ]
  • [ 15260-10-3 ]
  • [ 61925-77-7 ]
  • [ 54613-99-9 ]
  • [ 40350-83-2 ]
  • KDCCTOOKKCKDKQCKOQKCCA-NH2, O: 4-trans-hydroxyproline [ No CAS ]
  • 18
  • [ 15761-38-3 ]
  • [ 369-26-6 ]
  • (S)-methyl 3-(2-((tert-butoxycarbonyl)amino)propanamido)-4-fluorobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
(S)-Methyl 3-(2-((tert-butoxycarbonyl)amino)propanamido)-4-fluorobenzoate (I-60)Iso-Butyl chloroformate (5.3 mmol) was added to a solution of A/-(fert-butoxycarbonyl)-L-alanine (5.0 mmol) and N-methylmorpholine (5.3 mmol) in THF (25 mL) at 0 °C. After stirring for 30 min, <strong>[369-26-6]methyl 3-amino-4-fluorobenzoate</strong> (5.3 mmol) was added as a solid and the resulting mixture was stirred for 16 hrs at room temperature. After removal of the solvent (aspirator), the residue was dissolved in EtOAc (50 mL) and washed with NaHCO3 (sat., 50 mL), HCl (0.1 M in H2O, 50 mL) and brine (50 mL). The organics was dried (MgSO4) and concentrated (aspirator). The crude material was purified by chromatography (silica gel, 0-40percent EtOAc/hexanes) to give 1-60. 1H NMR (600 MHz, CDCl3): delta 8.96 (dd, J = 2.0, 7.6 Hz, 1 H), 8.67 (br s, 1 H), 7.83 - 7.75 (m, 1 H), 7.17 - 7.11 (m, 1 H), 4.94 (br s, 1 H), 4.36 (br s, 1 H), 3.90 (s, 3H), 1.50 - 1.43 (m, 12H).
  • 19
  • [ 15761-39-4 ]
  • [ 13734-41-3 ]
  • [ 13139-15-6 ]
  • [ 15761-38-3 ]
  • [ 13726-85-7 ]
  • [ 29022-11-5 ]
  • [ 13734-34-4 ]
  • [ 13836-37-8 ]
  • 2-(decyldisulfanyl)pyridine [ No CAS ]
  • [ 23680-31-1 ]
  • [ 122889-11-6 ]
  • [ 73821-97-3 ]
  • [ 54613-99-9 ]
  • [ 25024-53-7 ]
  • fmoc-S-4-methoxytrityl-L-cysteine [ No CAS ]
  • C151H256N48O39S [ No CAS ]
YieldReaction ConditionsOperation in experiment
10.2% The titled peptide was synthesized on a model 430A peptide synthesizer (Applied Rio systems, Foster City, Calif., U.S.A.) which was modified to do accelerated Hoc-chemistry solid phase peptide synthesis (Schnolzer, M. et al., mt. J Peptide Protein Res., (1992), 40:180). 4-Methylbenzhydry- lamine (MHHA) resin (Peninsula, Helmont, Calif., U.S.A.), with a substitution of0.91 mmol/g was used. Hoc amino acids (Midwest Hio-Tech, Fishers, Ind., U.S.A.; Novabiochem., San Diego, Calif., U.S.A.) were used with the following side chain protection: Hoc-Ala-OH, Hoc-Arg(Tos)-OH, Hoc-His (DNP)-OH, Hoc-Val-OH, Hoc-Ecu-OH, Hoc-Gly-OH, HocGln-OH, Hoc-Eys(2C1Z)?--OH, Hoc-Ser(Hzl)-OH, Hoc-PheOH, Hoc-Glu(OcHex)-OH and Hoc-Pro-OH. Fmoc-Glu (OtHu)-OH (Novabiochem, San Diego, Calif., U.S.A.) was used for the residue at the 3rd position in the sequence. The synthesis was carried out on a 0.25 mmol scale. The Hoc groups were removed by two treatments with 100percent TFA each lasting one minute. Hoc amino acids (2.5 mmol) were preactivated with HH11J (2.0 mmol) and DIEA (1.0 mE) in 4 mE of DMF and were coupled without prior neutralization of the peptide-resin TFA salt. Coupling times were 5 minutes. At the end of the assembly of the first 25 residues on theAHI 430A® peptide synthesizer and before the coupling of Fmoc-Glu (OtHu)-OH, the protected peptide-resin was transferred into a reaction vessel on a shaker for manual synthesis. After removing the Hoc protecting group with two, one-minute treatments with 100percent TFA and a washing with DMF, the resin was mixed with Fmoc-Glu(OtHu)-OH (2.5 mmol) which was preactivated with HHTU (2.0 mmol), HOHt (2.0 mmol) and DIEA (1.0 mE) in 4 mE of DMF. The mixture was shaken for 2 hours. This coupling step was repeated. After washing with DMF, the resin was treated with a TFA solution containing 5percent water and 5percent TIS for 2 hours to remove the tHu protecting group in the side chain of the Glu residue. The resin was neutralized with 10percent DIEA in DMF and washed with DMF and DCM. The resin was then treated twice with hexylamine (2.0 mmol), DIC (2.0 mmol), HOHt (2.0 mmol) in 5 ml of DCM for two hours per treatment. The resin was washed with DMF and treated with 25percent piperidine in DMF for 30 minutes to remove the Fmoc protecting group. Afier washing with DMF and DCM, the resin was transferred into the reaction vessel on the AHI 430A peptide synthesizer for the assembly of the rest two residues. At the end of the assembly of the whole peptide chain, the resin was treated with a solution of 20percent mercaptoethanol/10percent DIEA in DMF for 2x30 mm to remove the DNP group on the His side chain. The N-terminal Hoc group was then removed by two treatments of 100percent TFA for 2 minutes. The peptide-resin was washed with DMF and DCM and dried under reduced pressure. The final cleavage was done by stirring the peptide-resin in 10 mE of HF containing 1 mE of anisole and dithiothreitol (50 mg) at 0° C. for 75 minutes. HF was removed by a flow of nitrogen. The residue was washed with ether (6x 10 mE) and extracted with 4N HOAc (6x10 mE). This crude product was purified on a reverse-phase preparative HPEC using a colunm (4x43 cm) of C18 DYNAMAX-100A°® (Varian, Walnut Creek, Calif., U.S.A.). The column was eluted with a linear gradient from 75percentAand25percent B to 55percentAand45percent B at flow rate of 10 mE/mm in an hour where A was 0.1percent TFA in water and B was 0.1percent TFA in acetonitrile. Fractions were collected and checked on an analytical HPEC. Those containing pure product were combined and lyophilized to dryness. 31.8 mg of a white solid was obtained. Purity was 89percent based on analytical HPEC analysis. Electro-spray ionization mass spectrometry (ESI MS) analysis gave the molecular weight at 3368.4 (in agreement with the calculated molecular weight of 3368.9).
  • 20
  • [ 15761-38-3 ]
  • [ 1479-58-9 ]
  • (S)-{1-[4-bromo-2-(2-fluoro-benzoyl)-phenylcarbamoyl]-ethyl}-carbamic acid tert-butyl ester [ No CAS ]
  • 21
  • [ 15761-38-3 ]
  • N6-[4,6-bis(1,7-dicarba-closo-dodecaboran-9-ylthio)-1,3,5-triazin-2-yl]-N2-(tert-butoxycarbonyl)-L-lysine [ No CAS ]
  • [ 86123-10-6 ]
  • [ 150629-67-7 ]
  • 1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan [ No CAS ]
  • [ 32926-43-5 ]
  • [ 143824-78-6 ]
  • C59H89B20N17O7S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.5 mg General procedure: The first four amino acids (from the C-terminus) of peptide 13 were coupled by automated peptide synthesis as described in the general section. Following coupling scheme was used: The remaining two amino acids of peptide 13 were coupled manually using a 5-fold molar excess of amino acid, FIOBt and DIC (75 pmol each) in DMF as solvent. In addition, the whole sequence of peptide 15 was prepared by manual synthesis on a Rink amide AM resin using the same reagent conditions. Following coupling scheme was applied: In case of peptide 15, the resin was treated with a capping solution of 10 % DIPEA and 10 % acetic anhydride in DCM (15 min, 500 pi) after loading with the first C-terminal amino acid. Removal of Fmoc protecting groups after each manual coupling step was accomplished by using 20 % piperidine in DMF (2 x 10 min, 500 mI each). Peptides 14 and 16 were entirely prepared by automated peptide synthesis as described in the general section. The coupling scheme was as follows: The first two C-terminal amino acids of peptide 17 and 18 were coupled by automated peptide synthesis as described in the general section. Following coupling scheme was used:The remaining three amino acids of peptide 17 and 18 were coupled manually using a 3-fold or 5- fold molar excess of the amino acid and a 5-fold molar excess of FIOBt and DIC (75 pmol each) in DMF as solvent. The coupling scheme was as follows: Removal of Fmoc protecting groups after each manual coupling step was accomplished by using 20 % piperidine in DMF (2 x 10 min, 500 pi each). For the removal of the Mmt protecting group in peptide 13, the resin was treated with a cleavage mixture consisting of 2 % TFA, 5 % TIS in DCM (8 x 2 min, 1 ml each). After each deprotection step, the resin was washed with DCM. Finally, the resin was incubated with 5 % DIPEA in DCM (2 x 10 min, 1 ml each). For the cleavage of the Dde protecting group in all other peptides (14-18), the resin was treated with 2 % hydrazine in DMF (10 x 10 min, 1 ml each). In case of peptide 14, the building block Fmoc-L-Dap(Mtt)-OFI was coupled manually in 3-fold molar excess with a 5-fold molar excess of FIOBt and DIC (75 pmol each) to the e-amino group of the C- terminal lysine. DMF was used as solvent and the coupling time was approximately 16 h. For peptide 16, the building block Fmoc-L-Dap(Fmoc)-OFI was coupled manually in 5-fold molar excess with FIOBt and DIC (75 pmol each) in DMF to the C-terminal lysine side-chain. The coupling time was 4 h. Subsequently, removal of the Fmoc protecting groups was achieved by using 20 % piperidine in DMF (2 x 10 min, 500 mI each). 6-TAMRA was coupled manually to peptide 16 using a 2-fold molar excess of the fluorophore, FIATU and DIPEA (30 pmol each) in DMF as solvent for 5 h. Afterwards, removal of the Mtt protecting group in peptide 16 was performed as described for the Mmt deprotection above.The carbaboranes were coupled manually in 3-fold molar excess per free lysine or Dap amino group, except for mlJ9b, which was coupled in 1.5-fold molar excess per free amino group. Coupling reactions were prepared as follows: Peptides 13, 14 and 17: 3 eq. m9b, 5 eq. FIOBt and 5 eq. DIC in DMF as solvent. Peptide 15: 3 eq. bm9x, 4 eq. FIOBt and 4 eq. DIC in DMF. Peptide 16: 3 eq. mlJ9b, 4 eq. FIOBt and 4 eq. DIC in DMF. Peptide 18: 1.5 eq. mlJ9b, 2 eq. FIOBt and 2 eq. DIC in DMF. All coupling reactions were performed overnight for approximately 16 h. Cleavage of conjugates 13-15 and 17 from the resin and simultaneous side chain deprotection was accomplished using a mixture of TFA/TA/EDT (90:7:3, 1 ml) for 3 h. Cleavage of conjugates 16 and 18 from the resin was achieved using a mixture of TFA/FhO (95:5, 1 ml) for 3 h. The crude conjugates were precipitated and washed with an ice-cold mixture of hexane/diethyl ether (3:1, v/v), dissolved in ACN/FI2O and subsequently lyophilized. The first purification of the crude conjugate 13 was performed by preparative RP-HPLC using a C18- column (Phenomenex Jupiter 5u 300 A: 250 mm c 21.2 mm, 5 pm, 300 A) with a flow rate of 10 ml/min and a linear gradient of 50 % to 80 % eluent B in A over 30 min. Conjugate 13 had to be purified a second time using a XBridge C18-column (Waters XBridge Peptide BEH C18 OBD: 250 mm c 19 mm, 10 pm, 130 A) with a flow rate of 15 ml/min and a linear gradient of 50 % to 80 % eluent B in A over 30 min. For purification of conjugate 14, a XBridge C18-column (Waters XBridge Peptide BEH C18 OBD: 250 mm c 19 mm, 10 pm, 130 A) with a flow rate of 15 ml/min and a linear gradient of 30 % to 60 % eluent B in A over 30 min was applied. Purification of the conjugates 15-17 was achieved using a Kinetex C18-column (Phenomenex Kinetex 5u XB-C18: 250 mm c 21.2 mm, 5 pm, 100 A) with a flow rate of 15 ml/min. For conjugate 15 and 16, a linear gradient of 40 % to 70 % eluent B in A over 30 min was used, whereas for conjugate 17 a gradient of 50 % to 80 % eluent B in A over 30 min was applied. Purification of the...
  • 22
  • [ 15761-38-3 ]
  • 1-(1’,2’ :3’,4’-di-O-isopropylidene-6’-deoxy-a-D-galactopyranos-6’-yI)-9-(carboxymethylthio)-1,7-dicarba-closo-dodecaborane(12) [ No CAS ]
  • [ 86123-10-6 ]
  • [ 150629-67-7 ]
  • 1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan [ No CAS ]
  • [ 32926-43-5 ]
  • [ 143824-78-6 ]
  • Nα,Nβ-di[(9-fluorenylmethyl)oxycarbonyl]-(S)-2,3-diaminopropionic acid [ No CAS ]
  • C69H106B20N14O19S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
9.7 mg General procedure: The first four amino acids (from the C-terminus) of peptide 13 were coupled by automated peptide synthesis as described in the general section. Following coupling scheme was used: The remaining two amino acids of peptide 13 were coupled manually using a 5-fold molar excess of amino acid, FIOBt and DIC (75 pmol each) in DMF as solvent. In addition, the whole sequence of peptide 15 was prepared by manual synthesis on a Rink amide AM resin using the same reagent conditions. Following coupling scheme was applied: In case of peptide 15, the resin was treated with a capping solution of 10 % DIPEA and 10 % acetic anhydride in DCM (15 min, 500 pi) after loading with the first C-terminal amino acid. Removal of Fmoc protecting groups after each manual coupling step was accomplished by using 20 % piperidine in DMF (2 x 10 min, 500 mI each). Peptides 14 and 16 were entirely prepared by automated peptide synthesis as described in the general section. The coupling scheme was as follows: The first two C-terminal amino acids of peptide 17 and 18 were coupled by automated peptide synthesis as described in the general section. Following coupling scheme was used:The remaining three amino acids of peptide 17 and 18 were coupled manually using a 3-fold or 5- fold molar excess of the amino acid and a 5-fold molar excess of FIOBt and DIC (75 pmol each) in DMF as solvent. The coupling scheme was as follows: Removal of Fmoc protecting groups after each manual coupling step was accomplished by using 20 % piperidine in DMF (2 x 10 min, 500 pi each). For the removal of the Mmt protecting group in peptide 13, the resin was treated with a cleavage mixture consisting of 2 % TFA, 5 % TIS in DCM (8 x 2 min, 1 ml each). After each deprotection step, the resin was washed with DCM. Finally, the resin was incubated with 5 % DIPEA in DCM (2 x 10 min, 1 ml each). For the cleavage of the Dde protecting group in all other peptides (14-18), the resin was treated with 2 % hydrazine in DMF (10 x 10 min, 1 ml each). In case of peptide 14, the building block Fmoc-L-Dap(Mtt)-OFI was coupled manually in 3-fold molar excess with a 5-fold molar excess of FIOBt and DIC (75 pmol each) to the e-amino group of the C- terminal lysine. DMF was used as solvent and the coupling time was approximately 16 h. For peptide 16, the building block Fmoc-L-Dap(Fmoc)-OFI was coupled manually in 5-fold molar excess with FIOBt and DIC (75 pmol each) in DMF to the C-terminal lysine side-chain. The coupling time was 4 h. Subsequently, removal of the Fmoc protecting groups was achieved by using 20 % piperidine in DMF (2 x 10 min, 500 mI each). 6-TAMRA was coupled manually to peptide 16 using a 2-fold molar excess of the fluorophore, FIATU and DIPEA (30 pmol each) in DMF as solvent for 5 h. Afterwards, removal of the Mtt protecting group in peptide 16 was performed as described for the Mmt deprotection above.The carbaboranes were coupled manually in 3-fold molar excess per free lysine or Dap amino group, except for mlJ9b, which was coupled in 1.5-fold molar excess per free amino group. Coupling reactions were prepared as follows: Peptides 13, 14 and 17: 3 eq. m9b, 5 eq. FIOBt and 5 eq. DIC in DMF as solvent. Peptide 15: 3 eq. bm9x, 4 eq. FIOBt and 4 eq. DIC in DMF. Peptide 16: 3 eq. mlJ9b, 4 eq. FIOBt and 4 eq. DIC in DMF. Peptide 18: 1.5 eq. mlJ9b, 2 eq. FIOBt and 2 eq. DIC in DMF. All coupling reactions were performed overnight for approximately 16 h. Cleavage of conjugates 13-15 and 17 from the resin and simultaneous side chain deprotection was accomplished using a mixture of TFA/TA/EDT (90:7:3, 1 ml) for 3 h. Cleavage of conjugates 16 and 18 from the resin was achieved using a mixture of TFA/FhO (95:5, 1 ml) for 3 h. The crude conjugates were precipitated and washed with an ice-cold mixture of hexane/diethyl ether (3:1, v/v), dissolved in ACN/FI2O and subsequently lyophilized. The first purification of the crude conjugate 13 was performed by preparative RP-HPLC using a C18- column (Phenomenex Jupiter 5u 300 A: 250 mm c 21.2 mm, 5 pm, 300 A) with a flow rate of 10 ml/min and a linear gradient of 50 % to 80 % eluent B in A over 30 min. Conjugate 13 had to be purified a second time using a XBridge C18-column (Waters XBridge Peptide BEH C18 OBD: 250 mm c 19 mm, 10 pm, 130 A) with a flow rate of 15 ml/min and a linear gradient of 50 % to 80 % eluent B in A over 30 min. For purification of conjugate 14, a XBridge C18-column (Waters XBridge Peptide BEH C18 OBD: 250 mm c 19 mm, 10 pm, 130 A) with a flow rate of 15 ml/min and a linear gradient of 30 % to 60 % eluent B in A over 30 min was applied. Purification of the conjugates 15-17 was achieved using a Kinetex C18-column (Phenomenex Kinetex 5u XB-C18: 250 mm c 21.2 mm, 5 pm, 100 A) with a flow rate of 15 ml/min. For conjugate 15 and 16, a linear gradient of 40 % to 70 % eluent B in A over 30 min was used, whereas for conjugate 17 a gradient of 50 % to 80 % eluent B in A over 30 min was applied. Purification of the...
  • 23
  • [ 15761-38-3 ]
  • 9‐(carboxymethylthio)‐1,7‐dicarba‐closododecaborane(12) [ No CAS ]
  • 6-TAMRA [ No CAS ]
  • [ 86123-10-6 ]
  • [ 150629-67-7 ]
  • 1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan [ No CAS ]
  • [ 32926-43-5 ]
  • [ 143824-78-6 ]
  • N2-(9-fluorenylmethyloxycarbonyl)-N3-(4-methyltrityl)-2,3-diaminopropanoic acid [ No CAS ]
  • [K6(Dap(TAMRA/m9b))]-GHRP-6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
5.8 mg General procedure: The first four amino acids (from the C-terminus) of peptide 13 were coupled by automated peptide synthesis as described in the general section. Following coupling scheme was used: The remaining two amino acids of peptide 13 were coupled manually using a 5-fold molar excess of amino acid, FIOBt and DIC (75 pmol each) in DMF as solvent. In addition, the whole sequence of peptide 15 was prepared by manual synthesis on a Rink amide AM resin using the same reagent conditions. Following coupling scheme was applied: In case of peptide 15, the resin was treated with a capping solution of 10 % DIPEA and 10 % acetic anhydride in DCM (15 min, 500 pi) after loading with the first C-terminal amino acid. Removal of Fmoc protecting groups after each manual coupling step was accomplished by using 20 % piperidine in DMF (2 x 10 min, 500 mI each). Peptides 14 and 16 were entirely prepared by automated peptide synthesis as described in the general section. The coupling scheme was as follows: The first two C-terminal amino acids of peptide 17 and 18 were coupled by automated peptide synthesis as described in the general section. Following coupling scheme was used:The remaining three amino acids of peptide 17 and 18 were coupled manually using a 3-fold or 5- fold molar excess of the amino acid and a 5-fold molar excess of FIOBt and DIC (75 pmol each) in DMF as solvent. The coupling scheme was as follows: Removal of Fmoc protecting groups after each manual coupling step was accomplished by using 20 % piperidine in DMF (2 x 10 min, 500 pi each). For the removal of the Mmt protecting group in peptide 13, the resin was treated with a cleavage mixture consisting of 2 % TFA, 5 % TIS in DCM (8 x 2 min, 1 ml each). After each deprotection step, the resin was washed with DCM. Finally, the resin was incubated with 5 % DIPEA in DCM (2 x 10 min, 1 ml each). For the cleavage of the Dde protecting group in all other peptides (14-18), the resin was treated with 2 % hydrazine in DMF (10 x 10 min, 1 ml each). In case of peptide 14, the building block Fmoc-L-Dap(Mtt)-OFI was coupled manually in 3-fold molar excess with a 5-fold molar excess of FIOBt and DIC (75 pmol each) to the e-amino group of the C- terminal lysine. DMF was used as solvent and the coupling time was approximately 16 h. For peptide 16, the building block Fmoc-L-Dap(Fmoc)-OFI was coupled manually in 5-fold molar excess with FIOBt and DIC (75 pmol each) in DMF to the C-terminal lysine side-chain. The coupling time was 4 h. Subsequently, removal of the Fmoc protecting groups was achieved by using 20 % piperidine in DMF (2 x 10 min, 500 mI each). 6-TAMRA was coupled manually to peptide 16 using a 2-fold molar excess of the fluorophore, FIATU and DIPEA (30 pmol each) in DMF as solvent for 5 h. Afterwards, removal of the Mtt protecting group in peptide 16 was performed as described for the Mmt deprotection above.The carbaboranes were coupled manually in 3-fold molar excess per free lysine or Dap amino group, except for mlJ9b, which was coupled in 1.5-fold molar excess per free amino group. Coupling reactions were prepared as follows: Peptides 13, 14 and 17: 3 eq. m9b, 5 eq. FIOBt and 5 eq. DIC in DMF as solvent. Peptide 15: 3 eq. bm9x, 4 eq. FIOBt and 4 eq. DIC in DMF. Peptide 16: 3 eq. mlJ9b, 4 eq. FIOBt and 4 eq. DIC in DMF. Peptide 18: 1.5 eq. mlJ9b, 2 eq. FIOBt and 2 eq. DIC in DMF. All coupling reactions were performed overnight for approximately 16 h. Cleavage of conjugates 13-15 and 17 from the resin and simultaneous side chain deprotection was accomplished using a mixture of TFA/TA/EDT (90:7:3, 1 ml) for 3 h. Cleavage of conjugates 16 and 18 from the resin was achieved using a mixture of TFA/FhO (95:5, 1 ml) for 3 h. The crude conjugates were precipitated and washed with an ice-cold mixture of hexane/diethyl ether (3:1, v/v), dissolved in ACN/FI2O and subsequently lyophilized. The first purification of the crude conjugate 13 was performed by preparative RP-HPLC using a C18- column (Phenomenex Jupiter 5u 300 A: 250 mm c 21.2 mm, 5 pm, 300 A) with a flow rate of 10 ml/min and a linear gradient of 50 % to 80 % eluent B in A over 30 min. Conjugate 13 had to be purified a second time using a XBridge C18-column (Waters XBridge Peptide BEH C18 OBD: 250 mm c 19 mm, 10 pm, 130 A) with a flow rate of 15 ml/min and a linear gradient of 50 % to 80 % eluent B in A over 30 min. For purification of conjugate 14, a XBridge C18-column (Waters XBridge Peptide BEH C18 OBD: 250 mm c 19 mm, 10 pm, 130 A) with a flow rate of 15 ml/min and a linear gradient of 30 % to 60 % eluent B in A over 30 min was applied. Purification of the conjugates 15-17 was achieved using a Kinetex C18-column (Phenomenex Kinetex 5u XB-C18: 250 mm c 21.2 mm, 5 pm, 100 A) with a flow rate of 15 ml/min. For conjugate 15 and 16, a linear gradient of 40 % to 70 % eluent B in A over 30 min was used, whereas for conjugate 17 a gradient of 50 % to 80 % eluent B in A over 30 min was applied. Purification of the...
  • 24
  • [ 15761-38-3 ]
  • 9‐(carboxymethylthio)‐1,7‐dicarba‐closododecaborane(12) [ No CAS ]
  • Fmoc-Lys(Mmt)-OH [ No CAS ]
  • [ 86123-10-6 ]
  • 1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan [ No CAS ]
  • [ 32926-43-5 ]
  • [ 143824-78-6 ]
  • HwAWfK(9‐(carboxymethylthio)‐1,7‐dicarba‐closododecaborane(12))‐NH2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
5.5 mg General procedure: The first four amino acids (from the C-terminus) of peptide 13 were coupled by automated peptide synthesis as described in the general section. Following coupling scheme was used: The remaining two amino acids of peptide 13 were coupled manually using a 5-fold molar excess of amino acid, FIOBt and DIC (75 pmol each) in DMF as solvent. In addition, the whole sequence of peptide 15 was prepared by manual synthesis on a Rink amide AM resin using the same reagent conditions. Following coupling scheme was applied: In case of peptide 15, the resin was treated with a capping solution of 10 % DIPEA and 10 % acetic anhydride in DCM (15 min, 500 pi) after loading with the first C-terminal amino acid. Removal of Fmoc protecting groups after each manual coupling step was accomplished by using 20 % piperidine in DMF (2 x 10 min, 500 mI each). Peptides 14 and 16 were entirely prepared by automated peptide synthesis as described in the general section. The coupling scheme was as follows: The first two C-terminal amino acids of peptide 17 and 18 were coupled by automated peptide synthesis as described in the general section. Following coupling scheme was used:The remaining three amino acids of peptide 17 and 18 were coupled manually using a 3-fold or 5- fold molar excess of the amino acid and a 5-fold molar excess of FIOBt and DIC (75 pmol each) in DMF as solvent. The coupling scheme was as follows: Removal of Fmoc protecting groups after each manual coupling step was accomplished by using 20 % piperidine in DMF (2 x 10 min, 500 pi each). For the removal of the Mmt protecting group in peptide 13, the resin was treated with a cleavage mixture consisting of 2 % TFA, 5 % TIS in DCM (8 x 2 min, 1 ml each). After each deprotection step, the resin was washed with DCM. Finally, the resin was incubated with 5 % DIPEA in DCM (2 x 10 min, 1 ml each). For the cleavage of the Dde protecting group in all other peptides (14-18), the resin was treated with 2 % hydrazine in DMF (10 x 10 min, 1 ml each). In case of peptide 14, the building block Fmoc-L-Dap(Mtt)-OFI was coupled manually in 3-fold molar excess with a 5-fold molar excess of FIOBt and DIC (75 pmol each) to the e-amino group of the C- terminal lysine. DMF was used as solvent and the coupling time was approximately 16 h. For peptide 16, the building block Fmoc-L-Dap(Fmoc)-OFI was coupled manually in 5-fold molar excess with FIOBt and DIC (75 pmol each) in DMF to the C-terminal lysine side-chain. The coupling time was 4 h. Subsequently, removal of the Fmoc protecting groups was achieved by using 20 % piperidine in DMF (2 x 10 min, 500 mI each). 6-TAMRA was coupled manually to peptide 16 using a 2-fold molar excess of the fluorophore, FIATU and DIPEA (30 pmol each) in DMF as solvent for 5 h. Afterwards, removal of the Mtt protecting group in peptide 16 was performed as described for the Mmt deprotection above.The carbaboranes were coupled manually in 3-fold molar excess per free lysine or Dap amino group, except for mlJ9b, which was coupled in 1.5-fold molar excess per free amino group. Coupling reactions were prepared as follows: Peptides 13, 14 and 17: 3 eq. m9b, 5 eq. FIOBt and 5 eq. DIC in DMF as solvent. Peptide 15: 3 eq. bm9x, 4 eq. FIOBt and 4 eq. DIC in DMF. Peptide 16: 3 eq. mlJ9b, 4 eq. FIOBt and 4 eq. DIC in DMF. Peptide 18: 1.5 eq. mlJ9b, 2 eq. FIOBt and 2 eq. DIC in DMF. All coupling reactions were performed overnight for approximately 16 h. Cleavage of conjugates 13-15 and 17 from the resin and simultaneous side chain deprotection was accomplished using a mixture of TFA/TA/EDT (90:7:3, 1 ml) for 3 h. Cleavage of conjugates 16 and 18 from the resin was achieved using a mixture of TFA/FhO (95:5, 1 ml) for 3 h. The crude conjugates were precipitated and washed with an ice-cold mixture of hexane/diethyl ether (3:1, v/v), dissolved in ACN/FI2O and subsequently lyophilized. The first purification of the crude conjugate 13 was performed by preparative RP-HPLC using a C18- column (Phenomenex Jupiter 5u 300 A: 250 mm c 21.2 mm, 5 pm, 300 A) with a flow rate of 10 ml/min and a linear gradient of 50 % to 80 % eluent B in A over 30 min. Conjugate 13 had to be purified a second time using a XBridge C18-column (Waters XBridge Peptide BEH C18 OBD: 250 mm c 19 mm, 10 pm, 130 A) with a flow rate of 15 ml/min and a linear gradient of 50 % to 80 % eluent B in A over 30 min. For purification of conjugate 14, a XBridge C18-column (Waters XBridge Peptide BEH C18 OBD: 250 mm c 19 mm, 10 pm, 130 A) with a flow rate of 15 ml/min and a linear gradient of 30 % to 60 % eluent B in A over 30 min was applied. Purification of the conjugates 15-17 was achieved using a Kinetex C18-column (Phenomenex Kinetex 5u XB-C18: 250 mm c 21.2 mm, 5 pm, 100 A) with a flow rate of 15 ml/min. For conjugate 15 and 16, a linear gradient of 40 % to 70 % eluent B in A over 30 min was used, whereas for conjugate 17 a gradient of 50 % to 80 % eluent B in A over 30 min was applied. Purification of the...
 

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