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Chemical Structure| 122889-11-6 Chemical Structure| 122889-11-6

Structure of Fmoc-D-Ser(Bzl)-OH
CAS No.: 122889-11-6

Chemical Structure| 122889-11-6

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Synonyms: N-[(9H-Fluoren-9-ylmethoxy)carbonyl]-O-(phenylmethyl)-D-serine

4.5 *For Research Use Only! Not for Human Use. We Do Not Sell to Patients.

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Product Details of [ 122889-11-6 ]

CAS No. :122889-11-6
Formula : C25H23NO5
M.W : 417.45
SMILES Code : O=C(O)[C@H](NC(OCC1C2=C(C3=C1C=CC=C3)C=CC=C2)=O)COCC4=CC=CC=C4
Synonyms :
N-[(9H-Fluoren-9-ylmethoxy)carbonyl]-O-(phenylmethyl)-D-serine
English Name :Fmoc-D-Ser(Bzl)-OH
MDL No. :MFCD00237032
InChI Key :DYBDGLCDMLNEMJ-HSZRJFAPSA-N
Pubchem ID :7019719

Safety of [ 122889-11-6 ]

Computational Chemistry of [ 122889-11-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 31
Num. arom. heavy atoms 18
Fraction Csp3 0.2
Num. rotatable bonds 10
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 115.55
TPSA ?

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

84.86 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.74
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

4.03
Log Po/w (WLOGP)?

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

4.04
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.

2.82
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

3.98
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.52

Water Solubility

Log S (ESOL):?

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

-4.74
Solubility 0.00765 mg/ml ; 0.0000183 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-5.52
Solubility 0.00127 mg/ml ; 0.00000305 mol/l
Class?

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

Moderately soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-7.5
Solubility 0.0000133 mg/ml ; 0.0000000318 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

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

Yes
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

Yes
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.

-5.99 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)

4.31

Application In Synthesis of [ 122889-11-6 ]

* 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 [ 122889-11-6 ]

[ 122889-11-6 ] Synthesis Path-Downstream   1~87

  • 2
  • [ 5350-57-2 ]
  • [ 122889-11-6 ]
  • [ 98694-89-4 ]
  • 3
  • [ 122889-11-6 ]
  • [ 125827-94-3 ]
  • (S)-3-Benzyloxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (2S,3R,4S,5S,6R)-5-benzyloxy-6-benzyloxymethyl-3-iodo-4-((2S,3R,4S,5S,6R)-3,4,5-triacetoxy-6-acetoxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yl ester [ No CAS ]
  • (S)-3-Benzyloxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (2R,3R,4S,5S,6R)-5-benzyloxy-6-benzyloxymethyl-3-iodo-4-((2S,3R,4S,5S,6R)-3,4,5-triacetoxy-6-acetoxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yl ester [ No CAS ]
  • (S)-3-Benzyloxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid (2R,3S,4S,5S,6R)-5-benzyloxy-6-benzyloxymethyl-3-iodo-4-((2S,3R,4S,5S,6R)-3,4,5-triacetoxy-6-acetoxymethyl-tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-yl ester [ No CAS ]
  • 4
  • [ 122889-11-6 ]
  • [ 2748-02-9 ]
  • [ 118235-08-8 ]
  • 5
  • [ 122889-11-6 ]
  • [ 83345-52-2 ]
  • 6
  • [ 122889-11-6 ]
  • [ 157506-72-4 ]
  • 10
  • [ 29022-11-5 ]
  • [ 122889-11-6 ]
  • [ 35661-40-6 ]
  • [ 108-24-7 ]
  • [ 198561-07-8 ]
  • Ac-Ser(Bzl)-Asp-Phe-Gly-OH [ No CAS ]
  • 11
  • [ 122889-11-6 ]
  • [ 202868-77-7 ]
  • 12
  • [ 122889-11-6 ]
  • 3-(6-azidomethyl-2,2-dimethyl-tetrahydro-furo[3,4-<i>d</i>][1,3]dioxol-4-yloxy)-2-(9<i>H</i>-fluoren-9-ylmethoxycarbonylamino)-propionic acid <i>tert</i>-butyl ester [ No CAS ]
  • 13
  • [ 122889-11-6 ]
  • 3-(6-azidomethyl-2,2-dimethyl-tetrahydro-furo[3,4-<i>d</i>][1,3]dioxol-4-yloxy)-2-(9<i>H</i>-fluoren-9-ylmethoxycarbonylamino)-propionic acid <i>tert</i>-butyl ester [ No CAS ]
  • 14
  • [ 122889-11-6 ]
  • [ 110797-35-8 ]
  • 15
  • [ 122889-11-6 ]
  • [ 849063-79-2 ]
  • 16
  • [ 122889-11-6 ]
  • [ 849063-78-1 ]
  • 18
  • [ 122889-11-6 ]
  • [ 675882-23-2 ]
  • 19
  • [ 122889-11-6 ]
  • H-Glo[-Ser(Bzl)-Gly-OH]-OH*TFA [ No CAS ]
  • 20
  • [ 122889-11-6 ]
  • Cbz-His-OH [ No CAS ]
  • (S,Z)-(1-benzyloxymethyl-3-methoxyallyl)carbamic acid 9H-fluoren-9-yl methyl ester [ No CAS ]
  • 21
  • [ 122889-11-6 ]
  • Cbz-His-OH [ No CAS ]
  • (S,E)-(1-benzyloxymethyl-3-methoxyallyl)carbamic acid 9H-fluoren-9-yl methyl ester [ No CAS ]
  • 24
  • [ 122889-11-6 ]
  • [ 84000-14-6 ]
  • 25
  • [ 122889-11-6 ]
  • [ 84000-16-8 ]
  • 26
  • [ 122889-11-6 ]
  • [ 118235-08-8 ]
  • 27
  • [ 540-88-5 ]
  • [ 122889-11-6 ]
  • [ 305836-50-4 ]
YieldReaction ConditionsOperation in experiment
77% With sulfuric acid; In dichloromethane; at 0℃; Example 9. N- [ (9H-Fluoren-9-vl) methoxvcarbonyl]-O- (benzyl)-D-serine t-Butyl ester. N- [ (9H-Fluoren-9-yl) methoxycarbonyl]-O- (benzyl)-D-serine (0.710 g, 1.70 mmole) in dichloromethane (8 mL) was treated with t-butyl acetate (3 mL) and concentrated sulfuric acid (40 1L) in a sealed flask at 0 °C. Upon completion (TLC), the reaction was quenched with of dichloromethane (10 mL) and saturated aqueous potassium bicarbonate (15 mL). The organic layer was washed with distilled water, and evaporated. The resulting residue was purified by flash column chromatography (98: 2 dichloromethane/methanol) to yield the title compound as a colorless oil (0.292 g, 77percent); lH NMR (CDC13) a 1.44 (s, 9H); 3.68 (dd, J = 2.9 Hz, J = 9.3 Hz, 1H); 3.87 (dd, J = 2.9 Hz, J = 9.3 Hz, 1H); 4.22 (t, J = 7.1 Hz, 1H); 4.30-4. 60 (m, 5H) ; 5.64-5. 67 (m, 1H); 7.25- 7.39 (m, 9H); 7.58-7. 61 (m, 2H); 7.73-7. 76 (m, 2H).
  • 28
  • C34H28N2O7 [ No CAS ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 122889-11-6 ]
  • [ 71989-31-6 ]
  • [ 71989-18-9 ]
  • [ 103213-32-7 ]
  • [ 86060-81-3 ]
  • [ 116611-64-4 ]
  • [ 223416-45-3 ]
YieldReaction ConditionsOperation in experiment
Chelmical synthesis: Peptides were synthesized on a Rink amide resin, 0.45 mmol/g [Fmoc-Cys(Trityl)-Wang; Novabiochem, San Diego, Calif.] usinig N-(9-fluorenyl)methoxycarboxyl chemistry and standard side chain protection except on cysteine residues. Cysteine residues were protected in pairs with either S-trityl on the first and third cysteines or S-acetamidomethyl on the second and fourth cysteines. Amino acid derivatives were from Advanced Chemtech (Louisville, Ky.). The peptides were removed from the resin and precipitated, and a two-step oxidation protocol was used to selectively fold the peptides as described previously (Luo et al., 1999). Briefly, the first disulfide bridge was closed by dripping the peptide into an equal volume of 20 mM potassium feliicyanide and 0.1 M Tris, pH 7.5. The solution was allowed to react for 30 min, and the monocyclic peptide was purified by reverse-phase HPLC. Simultaneous removal of the S-acetamidomethyl groups and closure of the second disulfide bridge was carried out by iodine oxidation. The monocyclic peptide and HPLC eluent was dripped into an equal volume of iodine (10 mM) in H20/trifluoroacetic acid/acetonitrile (78:2:20 by volume) and allowed to react for 10 min. The reaction was terminated by the addition of ascorbic acid diluted 20-fold with 0.1percent trifluoroacetic acid and the bicyclic product purified by HPLC. Mass Spectrometry: Measurements were performed at the Salk Institute for Biological Studies (San Diego, Calif.) under the direction of Jean Rivier. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry and liquid secondary ionization mass spectrometry were used.
YieldReaction ConditionsOperation in experiment
Steps 3 through 6 were then repeated with the following order of amino acids:Fmoc-Cys(Acm)Fmoc-Ser(Bzl)Fmoc-Gly
  • 30
  • [ 10065-72-2 ]
  • [ 122889-11-6 ]
  • [ 1013917-04-8 ]
  • 31
  • [ 2627-86-3 ]
  • [ 122889-11-6 ]
  • [ 877669-40-4 ]
  • 32
  • [ 3886-69-9 ]
  • [ 122889-11-6 ]
  • [ 877669-42-6 ]
  • 33
  • [ 122889-11-6 ]
  • [ 618-36-0 ]
  • [ 877669-39-1 ]
  • 34
  • C41H42ClN2O7Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C66H63ClN3O11Pol [ No CAS ]
  • 35
  • C36H46ClO3Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C61H67ClNO7Pol [ No CAS ]
  • C61H67ClNO7Pol [ No CAS ]
  • 36
  • C36H46ClO3Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C61H67ClNO7Pol [ No CAS ]
  • C61H67ClNO7Pol [ No CAS ]
  • 37
  • C36H46ClO3Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C61H67ClNO7Pol [ No CAS ]
  • C61H67ClNO7Pol [ No CAS ]
  • 38
  • C36H46ClO3Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C61H67ClNO7Pol [ No CAS ]
  • C61H67ClNO7Pol [ No CAS ]
  • 40
  • C14H17N2O2Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C39H38N3O6Pol [ No CAS ]
  • 41
  • [ 35661-60-0 ]
  • [ 122889-11-6 ]
  • [ 1122068-68-1 ]
  • 42
  • [ 35661-60-0 ]
  • [ 122889-11-6 ]
  • [ 1098162-71-0 ]
  • 43
  • [ 1202878-73-6 ]
  • [ 122889-11-6 ]
  • [ 1202878-74-7 ]
  • 44
  • [ 98946-18-0 ]
  • [ 122889-11-6 ]
  • [ 202868-77-7 ]
  • 45
  • C18H21N2O4Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C43H42N3O8Pol [ No CAS ]
  • 46
  • C33H34N3O5Pol [ No CAS ]
  • [ 29022-11-5 ]
  • [ 35661-39-3 ]
  • [ 122889-11-6 ]
  • [ 35661-40-6 ]
  • [ 71989-33-8 ]
  • [ 71989-14-5 ]
  • [ 71989-18-9 ]
  • [ 71989-35-0 ]
  • [ 109425-51-6 ]
  • His-Ala-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Ser(OBn)-[2-amino-3-(biphenyl-4-yl)propanoyl]-NH2 [ No CAS ]
  • 48
  • fmoc-Leu-Alko Resin [ No CAS ]
  • [ 110-15-6 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 122889-11-6 ]
  • [ 71989-31-6 ]
  • [ 71989-38-3 ]
  • Cap1-PLG-S(OBn)YL; Cap1 = succinic acid [ No CAS ]
  • 49
  • fmoc-Leu-Alko Resin [ No CAS ]
  • [ 123-43-3 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 122889-11-6 ]
  • [ 71989-31-6 ]
  • [ 71989-38-3 ]
  • [ 1218936-53-8 ]
  • 50
  • fmoc-Leu-Alko Resin [ No CAS ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 121-53-9 ]
  • [ 122889-11-6 ]
  • [ 71989-31-6 ]
  • [ 71989-38-3 ]
  • Cap3-PLG-S(OBn)YL; Cap3 = 3-sulfobenzoic acid [ No CAS ]
  • 51
  • fmoc-Leu-Alko Resin [ No CAS ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 122889-11-6 ]
  • [ 71989-31-6 ]
  • [ 71989-38-3 ]
  • [ 64-19-7 ]
  • Ac-PLG-S(OBn)YL [ No CAS ]
  • 52
  • C9H10NO2Pol [ No CAS ]
  • [ 122889-11-6 ]
  • [ 86123-10-6 ]
  • [ 84624-17-9 ]
  • [ 135673-97-1 ]
  • [ 1252661-22-5 ]
  • 53
  • [ 122889-11-6 ]
  • (2-benzyloxy-1-hydroxycarbamoyl-ethyl)-carbamic acid 9<i>H</i>-fluoren-9-ylmethyl ester [ No CAS ]
  • 54
  • [ 186581-53-3 ]
  • [ 122889-11-6 ]
  • C26H23N3O4 [ No CAS ]
  • 55
  • (2S)-2-(4-phenyl-1H-imidazol-2-yl)pyrrolidine-1-carboxylate hydrochloride [ No CAS ]
  • [ 122889-11-6 ]
  • [ 1252036-05-7 ]
  • 56
  • (2S,3R)-2((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-methylpentanoic acid [ No CAS ]
  • C27H34NO7PolSi [ No CAS ]
  • [ 122889-11-6 ]
  • [ 103478-62-2 ]
  • C50H68N3O12PolSi [ No CAS ]
  • 57
  • [ 122889-11-6 ]
  • (3S,6R,12aR)-6-benzo[1,3]dioxol-5-yl-3-benzyloxymethyl-2,3,6,7,12,12a-hexahydropyrazino[1',2':1,6]pyrido[3,4-b]indole-1,4-dione [ No CAS ]
  • 58
  • [ 122889-11-6 ]
  • C45H39N3O8 [ No CAS ]
  • 59
  • [ 122889-11-6 ]
  • (S)-methyl 2-(3-((S)-1-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-(benzyloxy)ethyl)ureido)-3-methylbutanoate [ No CAS ]
  • 60
  • [ 122889-11-6 ]
  • [ 611198-33-5 ]
  • 61
  • [ 122889-11-6 ]
  • (S)-(9H-fluoren-9-yl)methyl 1-azido-3-(benzyloxy)-1-oxopropan-2-ylcarbamate [ No CAS ]
  • 62
  • [ 122889-11-6 ]
  • [ 530-62-1 ]
  • C28H25N3O4 [ No CAS ]
  • 63
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-60-0 ]
  • [ 152338-45-9 ]
  • [ 185031-78-1 ]
  • [ 122889-11-6 ]
  • [ 71989-31-6 ]
  • [ 71989-23-6 ]
  • [ 117872-75-0 ]
  • [ 136050-67-4 ]
  • GTCNTPGCTCSWPVCQIPGLGPLCGETCVG cyclic (3->15),(8->24),(10->28)-tris(disulfide) [ No CAS ]
  • 64
  • [ 35661-39-3 ]
  • C24H29NO6 [ No CAS ]
  • [ 122889-11-6 ]
  • [ 71989-23-6 ]
  • (3S,7S,10S,13S)-3-((3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-13-(benzyloxymethyl)-10-sec-butyl-7-methyl-5,8,11-trioxo-1-phenyl-2,6,9,12-tetraazatetradecan-14-oic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% General procedure: The peptides were synthesized on an activated [44] 2-chlorotrityl chloride resin (1 g) which had been swelled in dry DCM for 30 min. The first Fmoc amino acid (4 equiv) was coupled to the resin manually using dry DCM (10 mL) and DIPEA (6 equiv) for 2 h under a N2 atmosphere. Resin substitution was then determined using the Fmoc UV assay. On 0.1 mM scale subsequent amino acids were also coupled manually using amino acid (0.20 mM, 2.5 mL), DIPEA (1 mM, 1.0 mL) and HBTU (0.50 mM, 1.0 mL) in DMF. The Fmoc group of amino acid was removed using 20percent piperidine?DMF (3 × 10 mL) for 30 min and the next amino acid and sugar amino acid 1a/b were coupled on resin using the same condition. The excess reagents were washed with DMF (2 × 7 mL) and DCM (2 × 7 mL). Cleavage from resin was performed manually, using a cleavage mixture of TFA?DCM [5:95percent (v/v), 3 × 10 mL] for 30 min. The crude compound was then purified using semi-preparative HPLC. All compounds were obtained in good yields.
  • 65
  • [ 35661-39-3 ]
  • C22H31NO8 [ No CAS ]
  • [ 122889-11-6 ]
  • [ 71989-23-6 ]
  • (2S)-2-((2S,3S)-2-((2S)-2-((3S)-3-amino-3-((3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)propanamido)propanamido)-3-methylpentanamido)-3-(benzyloxy)propanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% General procedure: The peptides were synthesized on an activated [44] 2-chlorotrityl chloride resin (1 g) which had been swelled in dry DCM for 30 min. The first Fmoc amino acid (4 equiv) was coupled to the resin manually using dry DCM (10 mL) and DIPEA (6 equiv) for 2 h under a N2 atmosphere. Resin substitution was then determined using the Fmoc UV assay. On 0.1 mM scale subsequent amino acids were also coupled manually using amino acid (0.20 mM, 2.5 mL), DIPEA (1 mM, 1.0 mL) and HBTU (0.50 mM, 1.0 mL) in DMF. The Fmoc group of amino acid was removed using 20percent piperidine?DMF (3 × 10 mL) for 30 min and the next amino acid and sugar amino acid 1a/b were coupled on resin using the same condition. The excess reagents were washed with DMF (2 × 7 mL) and DCM (2 × 7 mL). Cleavage from resin was performed manually, using a cleavage mixture of TFA?DCM [5:95percent (v/v), 3 × 10 mL] for 30 min. The crude compound was then purified using semi-preparative HPLC. All compounds were obtained in good yields.
  • 66
  • C22H31NO8 [ No CAS ]
  • [ 122889-11-6 ]
  • (3S,6S,9S,13S)-13-((3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-3-(benzyloxymethyl)-6-sec-butyl-9-methyl-1,4,7,10-tetraazacyclotridecane-2,5,8,11-tetraone [ No CAS ]
  • 67
  • [ 122889-11-6 ]
  • 2-amino-3-(benzyloxy)-N-(4-(2-(4-methoxyphenyl)-4-oxo-1-(3,4,5-trimethoxy phenyl)azetidin-3-yl)phenyl)propanamide [ No CAS ]
  • 68
  • [ 122889-11-6 ]
  • 2-amino-3-(benzyloxy)-N-(2-methoxy-5-(4-oxo-3-phenyl-1-(3,4,5-trimethoxyphenyl)azetidin-2-yl)phenyl)propanamide [ No CAS ]
  • 69
  • C25H26N2O5 [ No CAS ]
  • [ 122889-11-6 ]
  • (9H-fluoren-9-yl)methyl (3-(benzyloxy)-1-((4-(2-(4-methoxyphenyl)-4-oxo-1-(3,4,5-trimethoxyphenyl)azetidin-3-yl)phenyl)amino)-1-oxopropan-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With 1-hydroxybenzotriazol-hydrate; dicyclohexyl-carbodiimide; In N,N-dimethyl-formamide; at 20℃; for 24h; General procedure: To a stirred solution of the appropriate amino beta-lactam 10 or 11 (4.76 mmol) in anhydrous DMF (30 mL) were added DCC (5.7 mmol), Cbz- or Fmoc-protected l-amino acid (5.7 mmol) and HOBt.H2O (7.3 mmol) at room temperature. After 24 hours, ethyl acetate (50 mL) was added and the mixture was filtered. DMF was removed by washing with water (5 × 50 mL). The organic layer containing the product was reduced in vacuo. The product was isolated by flash column chromatography (dichlormethane: methanol gradient).#10;#10;
  • 70
  • C25H26N2O5 [ No CAS ]
  • [ 122889-11-6 ]
  • (9H-fluoren-9-yl)methyl (3-(benzyloxy)-1-((2-methoxy-5-(4-oxo-3-phenyl-1-(3,4,5-trimethoxyphenyl)azetidin-2-yl)phenyl)amino)-1-oxopropan-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With 1-hydroxybenzotriazol-hydrate; dicyclohexyl-carbodiimide; In N,N-dimethyl-formamide; at 20℃; for 24h; General procedure: To a stirred solution of the appropriate amino beta-lactam 10 or 11 (4.76 mmol) in anhydrous DMF (30 mL) were added DCC (5.7 mmol), Cbz- or Fmoc-protected l-amino acid (5.7 mmol) and HOBt.H2O (7.3 mmol) at room temperature. After 24 hours, ethyl acetate (50 mL) was added and the mixture was filtered. DMF was removed by washing with water (5 × 50 mL). The organic layer containing the product was reduced in vacuo. The product was isolated by flash column chromatography (dichlormethane: methanol gradient).#10;#10;
  • 71
  • C7H12N3O2Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C32H33N4O6Pol [ No CAS ]
  • 72
  • [ 122889-11-6 ]
  • [ 84000-14-6 ]
  • 73
  • C17H24N3O3(1+)*F6P(1-) [ No CAS ]
  • [ 122889-11-6 ]
  • C42H45N4O7(1+)*F6P(1-) [ No CAS ]
  • 74
  • C54H79Cl3N7O16Si(1+)*F6P(1-) [ No CAS ]
  • [ 122889-11-6 ]
  • C82H105Cl3N9O21Si(1+)*F6P(1-) [ No CAS ]
  • 75
  • [ 35661-39-3 ]
  • [ 1427040-55-8 ]
  • [ 122889-11-6 ]
  • [ 71989-23-6 ]
  • [ 122350-52-1 ]
  • (6S,9S,12S,15S)-6-{(S)-3-amino-3-[(3aR,5R,6S,6aR)-6-(benzyloxy)-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl]propanamido}-15-(benzyloxymethyl)-12-sec-butyl-9-methyl-3,7,10,13-tetraoxo-1-phenyl-2-oxa-8,11,14-triazahexadecan-16-oic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% The peptide 4 was synthesized manually on an activated 2-chlorotrityl chloride resin (1 g) which had been swelled in dry DCM for 30 min. The first amino acid Fmoc-Ser-OH was coupled to the resin using dry DCM (10 mL) and DIPEA (6.65 mmol) for 2 h under a N2 atmosphere. Resin substitution was 0.6 mol g?1 as determined by the Fmoc UV assay. The Fmoc group of serine was removed using 20 percent piperidine in DMF (3 × 10 mL) for30 min. Subsequently, amino acids Fmoc-Ile-OH, Fmoc-Ala-OH,and Fmoc-Glu-OH (0.20 mM) were coupled using DIPEA (1 mM) and HCTU (0.50 mM) in DMF. The Fmoc group of glutamic acid was removed using 20 percent piperidine in DMF (3 ×10 mL) for 30 min and finally sugar amino acid 1 was coupled using DIPEA (1 mM) and HCTU (0.50 mM) in DMF. Standardwashing procedures were used. Cleavage from the resin was performed, using a cleavage mixture of 5 percent TFA in DCM (3 ×10 mL)for 30 min. The crude compound was then purified usingsemi-preparative HPLC on a Shimadzu Instrument LC-8A (AceC18 150 mm × 21.2 mm × 5 mm) with an UV/VIS detector SPD-M20A (215nmand 254 nm) and automated fraction collector FRC-10a with 15mLmin?1 flow rate and two buffer system waterand MeOH containing 0.1 percent HCOOH with method RP-HPLC:5 percent MeOH /95 percent H2O/0.1 percent HCOOH to 95 percent MeOH /5 percentH2O/0.1 percent HCOOH in 35 min. Compound 4 was obtained in 64 percent yield as a white solid, mp 171 °C.
  • 76
  • [ 122889-11-6 ]
  • [ 378247-75-7 ]
  • C21H21N3O5 [ No CAS ]
  • 77
  • [ 35661-60-0 ]
  • [ 122889-11-6 ]
  • [ 71989-14-5 ]
  • [ 64-19-7 ]
  • [ 378247-75-7 ]
  • Fmoc-Glu(pg)-OH [ No CAS ]
  • C38H46N6O13 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Synthesis of NH2-ACC-Rink Amide resin. Preparation of ACC wascarried out as described previously according to Maly et al.18 To glass reactionvessel, 1 eq (6.24 mmol, 13 g) of Rink AM resin was added and stirred gentlyonce per 10 min in DCM for 1 h, and then filtered and washed 3 times with DMF.Fmoc-protecting group was removed using 20percent piperidine in DMF (5, 5, and25 min), filtered each time and washed with DMF (six times). Next, 2.50 eq of Fmoc-ACC-OH (15.6 mmol, 6.9 g) was preactivated with 2.50 eq HOBt monohydrate (15.6 mmol, 2.34 g) and 2.50 eq DICI (15.6 mmol, 2.0 ml) in DMFand mixture was added to the resin. Reaction was stirred gently for 24 h at room temperature. Resin was washed four times with DMF and reaction was repeatedusing 1.5 eq of above reagents to improve yield of ACC coupling to the resin. Afterreaction, resin was washed with DMF and Fmoc group was removed using 20percentpiperidine in DMF (5, 5, and 25 min), filtered and washed with DMF (six times). Synthesis of NH2-Asp(t-Bu)-ACC-Rink Amide resin. Next, 2.5 eqFmoc-Asp(t-Bu)-OH (15.6 mmol, 6.42 g) with 2.5 eq HATU (15.6 mmol, 5.93 g),2.5 eq collidine (15.6 mmol, 2.03 ml) in DMF were activated for 2 min and added tofilter cannula with 1 eq (6.24 mmol) NH2-ACC-resin and reaction was carried outfor 24 h. Next, resin was washed four times with DMF and reaction was repeatedusing 1.5 eq of above reagents. After washing with DMF, Fmoc-protecting groupwas removed using 20percent piperidine in DMF (5, 5, and 25 min). Resin wasadditional washed with DCM (3 times) and MeOH (3 times) and dried over P2O5. Synthesis of individual optimized substrates. The 2.5 eqFmoc-P2-OH was preactivated with 2.5 eq HOBt and 2.5 eq DICI in DMF andadded to cartridge with 1 eq NH2-Asp(t-Bu)-ACC-resin (all substrates containedAsp at P1 position) and followed by gentle agitation for 3 h. Then, it was filteredand washed with DMF (six times). Fmoc-protecting group was removed using 20percent piperidine in DMF (5, 5, and 25 min). Ninhydrin test was carried out each time aftercoupling and deprotection. A solution of 2.5 eq Fmoc-P3-OH, 2.5 eq HOBt, and2.5 eq DICI in DMF was added to the resin and the slurry was agitated for 3 h.After removal of the solution, the resin was washed with DMF (six times), andcoupling and deprotection of Fmoc-P4-OH was carried in identical conditions likeP2 position. N-terminus was protected with acetyl group using 5 eq AcOH, 5 eqHBTU, and 5 eq DIPEA in DMF as previous described. After solvent removal, theresin was washed with DMF (six times), DCM (three times), and MeOH (threetimes) dried over P2O5 and cleaved from the resin with a mixture of TFA/TIPS/H2O(percent, v/v/v 95 : 2.5 : 2.5). The crude product was purified by HPLC and lyophilized.Its purity was confirmed by analytical HPLC. Each optimized substrate wasanalyzed using HRMS. Optimized substrates were dissolved in peptide gradeDMSO to 20mM concentration and stored at -80 °Cuntil use.
  • 80
  • [ 6456-74-2 ]
  • [ 122889-11-6 ]
  • [ 675882-22-1 ]
YieldReaction ConditionsOperation in experiment
85% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere; Amino acid S30 (27 mg, 0.065 mmol) and S31 (10 mg, 0.0599 mmol) were dissolved in 0.6 mL dry DMF, followed by addition of HATU (30mg, 0.077mmol), DIPEA (25|xL 0.1797 mmol). The resulting mixture was stirred under room temperature overnight and diluted with EtOAc. The solution was washed with 1M HCl and a saturated aqueous NaHCO3 solution. The combined organic phase was dried over Na2SO4 and concentrated, purified by silica gel column to afford compound S32 (27 mg, 85percent).
  • 81
  • [ 13734-34-4 ]
  • C13H19N4O5Pol [ No CAS ]
  • [ 122889-11-6 ]
  • C37H47N6O10Pol [ No CAS ]
  • 82
  • [ 122889-11-6 ]
  • Fmoc-Ser(OBn)ψCH3 [ No CAS ]
  • 83
  • Fmoc-alanine-Wang-resin [ No CAS ]
  • [ 122889-11-6 ]
  • [ 108-24-7 ]
  • [ 71989-23-6 ]
  • N-acetyl-L-isoleucyl-L-(OBn)seryl-L-alanine [ No CAS ]
  • 84
  • [ 122889-11-6 ]
  • (3R,S,4S)-(4-(N-acetyl-L-isoleucyl-L-(OBn)seryl-L-alanylamino)-2,2-difluoro-3-hydroxypentanoyl)glycine benzyl ester [ No CAS ]
  • 85
  • [ 122889-11-6 ]
  • (4S)-(4-(N-acetyl-L-isoleucyl-L-(OBn)seryl-L-alanylamino)-2,2-difluoro-3-oxopentanoyl)glycine benzyl ester [ No CAS ]
  • 86
  • [ 122889-11-6 ]
  • (4S)-(4-(N-acetyl-L-isoleucyl-L-(OBn)seryl-L-alanylamino)-2,2-difluoro-3-oxopentanoyl)glycine [ No CAS ]
  • 87
  • [ 67-56-1 ]
  • H-Gly-(2-Cl)-Trt-pol [ No CAS ]
  • [ 29022-11-5 ]
  • [ 68858-20-8 ]
  • [ 35661-39-3 ]
  • [ 291754-76-2 ]
  • [ 122889-11-6 ]
  • [ 71989-31-6 ]
  • C37H55N7O13 [ No CAS ]
 

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Technical Information

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