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Chemical Structure| 67436-13-9 Chemical Structure| 67436-13-9

Structure of Fmoc-Cys(tBu)-OH
CAS No.: 67436-13-9

Chemical Structure| 67436-13-9

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Synonyms: N-(((9H-Fluoren-9-yl)methoxy)carbonyl)-S-(tert-butyl)-L-cysteine

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Product Details of [ 67436-13-9 ]

CAS No. :67436-13-9
Formula : C22H25NO4S
M.W : 399.50
SMILES Code : O=C(O)[C@H](CSC(C)(C)C)NC(OCC1C2=CC=CC=C2C3=CC=CC=C13)=O
Synonyms :
N-(((9H-Fluoren-9-yl)methoxy)carbonyl)-S-(tert-butyl)-L-cysteine
MDL No. :MFCD00037130
InChI Key :IXAYZHCPEYTWHW-IBGZPJMESA-N
Pubchem ID :7009544

Safety of [ 67436-13-9 ]

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

Computational Chemistry of [ 67436-13-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 28
Num. arom. heavy atoms 12
Fraction Csp3 0.36
Num. rotatable bonds 9
Num. H-bond acceptors 4.0
Num. H-bond donors 2.0
Molar Refractivity 112.03
TPSA ?

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

100.93 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.55
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

4.32
Log Po/w (WLOGP)?

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

4.51
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.

3.22
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

3.92
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.7

Water Solubility

Log S (ESOL):?

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

-4.76
Solubility 0.00692 mg/ml ; 0.0000173 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.

-6.15
Solubility 0.00028 mg/ml ; 0.000000702 mol/l
Class?

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

Poorly 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

-6.17
Solubility 0.000269 mg/ml ; 0.000000673 mol/l
Class?

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

Poorly 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

Yes
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.

-5.67 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)

4.33

Application In Synthesis of [ 67436-13-9 ]

* 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 [ 67436-13-9 ]

[ 67436-13-9 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 66-77-3 ]
  • [ 67436-13-9 ]
  • [ 96402-49-2 ]
  • [ 541-88-8 ]
  • (R)-N-α-Fmoc-N-ε-Boc-lysinal [ No CAS ]
  • (S)-2-{(R)-6-(4-Amino-butyl)-9-[(naphthalen-1-ylmethyl)-amino]-3,8-dioxo-[1,4,7]thiadiazecan-4-yl}-3-naphthalen-1-yl-propionic acid [ No CAS ]
  • (S)-2-{(R)-6-(4-Amino-butyl)-9-[(naphthalen-1-ylmethyl)-amino]-3,8-dioxo-[1,4,7]thiadiazecan-4-yl}-3-naphthalen-1-yl-propionamide [ No CAS ]
  • 2
  • [ 66-77-3 ]
  • [ 67436-13-9 ]
  • [ 96402-49-2 ]
  • [ 541-88-8 ]
  • (S)-N-α-Fmoc-N-ε-Boc-lysinal [ No CAS ]
  • (S)-2-{(R)-6-(4-Amino-butyl)-9-[(naphthalen-1-ylmethyl)-amino]-3,8-dioxo-[1,4,7]thiadiazecan-4-yl}-3-naphthalen-1-yl-propionic acid [ No CAS ]
  • (S)-2-{(R)-6-(4-Amino-butyl)-9-[(naphthalen-1-ylmethyl)-amino]-3,8-dioxo-[1,4,7]thiadiazecan-4-yl}-3-naphthalen-1-yl-propionamide [ No CAS ]
  • 3
  • [ 66-77-3 ]
  • [ 67436-13-9 ]
  • [ 96402-49-2 ]
  • [ 541-88-8 ]
  • (S)-N-α-Fmoc-N-ε,N-γ-di-Boc-arginal [ No CAS ]
  • (S)-2-{(R)-6-(3-Guanidino-propyl)-9-[(naphthalen-1-ylmethyl)-amino]-3,8-dioxo-[1,4,7]thiadiazecan-4-yl}-3-naphthalen-1-yl-propionamide [ No CAS ]
  • (S)-2-{(R)-6-(3-Guanidino-propyl)-9-[(naphthalen-1-ylmethyl)-amino]-3,8-dioxo-[1,4,7]thiadiazecan-4-yl}-3-naphthalen-1-yl-propionic acid [ No CAS ]
  • 4
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 71989-31-6 ]
  • [ 35661-40-6 ]
  • [ 67436-13-9 ]
  • [ 73724-45-5 ]
  • [ 96402-49-2 ]
  • [ 109425-51-6 ]
  • Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine [ No CAS ]
  • Fmoc-Lys(Boc)-OH [ No CAS ]
  • Fmoc-Glu(OtBu)-OH [ No CAS ]
  • Fmoc-Met-OH [ No CAS ]
  • acetic anhydride [ No CAS ]
  • Ac-(cyclo 1-20)-CPEMREKLSGHHFVRALARCSGGPR(1Nal)-NH2 [ No CAS ]
  • 5
  • C23H27N2O4Pol [ No CAS ]
  • [ 29022-11-5 ]
  • [ 920519-33-1 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 67436-13-9 ]
  • [ 86060-81-3 ]
  • [ 102410-65-1 ]
  • mouse linear [A10,A22]-hepcidin-1 (C7: SH, C23: SH; C11: S-Acm, C19: S-Acm; C13: S-tBu, C14: S-tBu) [ No CAS ]
  • 6
  • C23H27N2O4Pol [ No CAS ]
  • [ 29022-11-5 ]
  • [ 920519-33-1 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 71989-26-9 ]
  • [ 103213-32-7 ]
  • [ 132388-59-1 ]
  • [ 132327-80-1 ]
  • [ 67436-13-9 ]
  • [ 86060-81-3 ]
  • [ 102410-65-1 ]
  • mouse linear [A11,A19]-hepcidin-2 (C7: SH, C23: SH; C10: S-Acm, C13: S-Acm; C14: S-tBu C22: S-tBu) [ No CAS ]
  • 7
  • [ 159610-93-2 ]
  • 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 ]
  • [ 71989-14-5 ]
  • [ 71989-35-0 ]
  • [ 132388-59-1 ]
  • [ 67436-13-9 ]
  • [ 119831-72-0 ]
  • FFC(Acm)PFGC(t-Bu)ALVDCGPNRPC(t-Bu)RDTGF-(L-O-methylhomoserinyl)-SC(Acm)DC [ No CAS ]
  • 8
  • [ 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 ]
YieldReaction ConditionsOperation 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 .
 

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