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Chemical Structure| 135544-68-2 Chemical Structure| 135544-68-2

Structure of Alloc-OSu
CAS No.: 135544-68-2

Chemical Structure| 135544-68-2

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Product Details of [ 135544-68-2 ]

CAS No. :135544-68-2
Formula : C8H9NO5
M.W : 199.16
SMILES Code : O=C(OCC=C)ON1C(CCC1=O)=O
MDL No. :MFCD02684388
InChI Key :OIXALTPBNZNFLJ-UHFFFAOYSA-N
Pubchem ID :11788855

Safety of [ 135544-68-2 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P362+P364-P332+P313

Computational Chemistry of [ 135544-68-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.38
Num. rotatable bonds 5
Num. H-bond acceptors 5.0
Num. H-bond donors 0.0
Molar Refractivity 47.95
TPSA ?

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

72.91 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.8
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

0.28
Log Po/w (WLOGP)?

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

0.01
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.

-0.07
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

0.12
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.43

Water Solubility

Log S (ESOL):?

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

-0.92
Solubility 23.9 mg/ml ; 0.12 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.

-1.37
Solubility 8.44 mg/ml ; 0.0424 mol/l
Class?

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

Very 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

-0.39
Solubility 81.3 mg/ml ; 0.408 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

Yes
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.

-7.32 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.

0.55

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

2.0 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)

2.32

Application In Synthesis of [ 135544-68-2 ]

* 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 [ 135544-68-2 ]

[ 135544-68-2 ] Synthesis Path-Downstream   1~5

  • 1
  • [ 132622-69-6 ]
  • [ 135544-68-2 ]
  • C14H22N2O6 [ No CAS ]
  • 2
  • [ 135544-68-2 ]
  • [ 1397-89-3 ]
  • C51H77NO19 [ No CAS ]
YieldReaction ConditionsOperation in experiment
100% With pyridine; In methanol; N,N-dimethyl-formamide; at 23℃; for 16h;Inert atmosphere; To a stirred suspension of AmB (4.0 g, 4.3 mmol, 1.0 equiv.) in DMF:MeOH (75 mL: 75 mL) in a 300 mL round bottom at 23 C, was added sequentially, pyridine (5.0 mL, 50.0 mmol, 11.5 equiv.), and alloc-succinimide (2.4 g, 12.05 mmol, 2.8 equiv.). After stirring for 16 h at 23 C, the dark orange, homogeneous solution was slowly poured into rapidly stirring Et20 (3.5 L). The yellow suspension was filtered through Whatman 42 filter paper and washed with Et20 (3 x 100 mL) before the cake was allowed to fully dry. The fully dried alloc-AmB yellow powder (4.3 mmol, quantitative) was taken on to the subsequent reaction without further purification.
100% In methanol; N,N-dimethyl-formamide; at 23℃; for 16h; To a stirred suspension of AmB (4.0 g, 4.3 mmol,1.0 equiv.) in DMF:MeOH (75 mE: 75 mE) in a 300 mE round bottom flask at 23 C. was added pyridine (5.0 mE, 50.0 mmol, 11.5 equiv.) and alloc-succinimide (2.4 g, 12.05 mmol, 2.8 equiv.). After stirring for 16 hat 23 C., the dark orange, homogeneous solution was slowly poured into rapidly stirring Et20 (3.5 E). The yellow suspension was filtered through Whatman 42 filter paper (110 mm diameter) and washed with Et20 (3x100 mE) before the cake was allowed to fully dry. The fully dried alloc-AmB yellow powder (4.3 mmol, quantitative) was taken on to the subsequent reaction without thrther purification.
With pyridine; In methanol; N,N-dimethyl-formamide; at 23℃; for 16h; To a stirred suspension of AmB (4.0 g, 4.3 mmol, 1.0 equiv.) in DMF:MeOH (75 mL: 75 mL) in a 300 mL round bottom flask at 23 C was added pyridine (5.0 mL, 50.0mmol, 11.5 equiv.) and alloc-succinimide (2.4 g, 12.05 mmol, 2.8 equiv.). After stirring for16 h at 23 C, the dark orange, homogeneous solution was slowly poured into rapidlystirring Et20 (3.5 L). The yellow suspension was filtered through Whatman 42 filter paper(110 mm diameter) and washed with Et20 (3 x 100 mL) before the cake was allowed tofully dry. The fully dried alloc-AmB yellow powder (4.3 mmol, quantitative) was taken onto the subsequent reaction without further purification.
With pyridine; In methanol; N,N-dimethyl-formamide; at 20℃; for 16h; To a stirred solution of Amphotericin B (25.0 g, 27.05 mmol) in DMF:MeOH (2:1, 750 ml) and pyridine (25 ml. 308.4 mmoi) was added allocsuccinimide (15.08 g, 75.75 mmoi) at room temperature. After 1 6h, the reaction mixture was poured into cold Et20. The resulting solid was filtered and dried under reduced pressure to provide a yellow solid. The solid compound was washed with diethyl ether (5 x 100 mL) to afford compound 2 I as a yellow solid. Compound 24 analysis: LC/MS (ESI) m/z 1006.4 [MH].
15.08 g With pyridine; In methanol; N,N-dimethyl-formamide; at 20℃; for 16h; EXAMPLE 1 [0094] Compound 1 (FIGURE 1 A) was prepared as follows (Figure IB): Step 1 : To a stirred solution of Amphotericin B (25.0 g, 27.05 mmol) in DMF: MeOH (2:1, 750 ml) and pyridine (25 ml, 308.4 mmol) was added alloc-succinimide (15.08 g, 75.75 mmol) at room temperature. After 16 h, the reaction mixture was poured into cold Et20. The resulting solid was filtered and dried under reduced pressure to provide a yellow solid. The solid compound was washed with diethyl ether (5 x 100 mL) to afford Compound 1-1 as a yellow solid. Compound 1-1 analysis: LC/MS (ESI) m/z 1006.4 [M-H]-.

  • 3
  • [ 67-56-1 ]
  • [ 2186-92-7 ]
  • [ 135544-68-2 ]
  • [ 1397-89-3 ]
  • C68H91NO21 [ No CAS ]
YieldReaction ConditionsOperation in experiment
54% A suitable fully protected intermediate was quickly generated from AmB (Scheme 3, FIG. 16). This sequence involved Alloc protection of the amine, C3/C5 and C9/C11 rho-methoxyphenyl acetal formation, TES silylation of the remaining alcohols, and lastly TMSE formation of the C16 carboxylate to form fully protected intermediate 5. Exposure of 5 to NaHMDS at low temperatures smoothly eliminated the C3 alcohol, generating an alpha-beta unsaturated lactone. Stryker reduction of this intermediate efficiently reduced the unsaturation yielding 6, leaving only a deprotection sequence to generate C3deOAmB. Exposure of 6 to HF cleanly removed the TES groups, followed by TBAF-promoted TMSE removal. Methyl ketal and PMP ketal hydrolysis was achieved concomitantly under acidic conditions with HCl. Efforts are currently underway to achieve the final Alloc deprotection of 7 and synthesize C3deOAmB.
  • 4
  • [ 135544-68-2 ]
  • [ 1397-89-3 ]
  • C50H75NO19 [ No CAS ]
  • 5
  • [ 1115-74-8 ]
  • [ 135544-68-2 ]
  • (S)-2-((S)-2-(((allyloxy)carbonyl)amino)-3-methylbutanamido)propanoic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
91% With sodium hydrogencarbonate; In water; acetone; at 20℃; for 16h; <strong>[1115-74-8](S)-2-((S)-2-amino-3-methylbutanamido)propanoic acid</strong> (1.74 g, 9.24 mmol), allyl (2,5-dioxopyrrolidin-1-yl) carbonate (1.84 g, 1 eq), NaHCO3 (776 mg, 1 eq), water (37 mL) and acetone (37 mL) was stirred at room temperature for 16 h. The acetone was removed by rotary evaporation, the residue was diluted with water (250 mL) and the pH adjusted to 3 using concentrated HCl (17 mL), followed by extraction with EtOAc (3×400 mL). The organic layer was dried over Na2SO4, filtered and evaporated to give ((allyloxy)carbonyl)-<strong>[1115-74-8]L-valyl-L-alanine</strong> (89) as a white solid (2.28 g, 91% yield). 1H NMR (DMSO-d6) delta 12.49 (s, 1H), 8.12 (d, 1H), 7.14 (d, 1H), 5.97 (m, 1H), 5.14 (d, 1H), 5.09 (d, 1H), 4.23 (s, 2H), 1.98 (m, 1H), 1.13 (d, 3H), 0.80 (m, 6H)
44% With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 3h; To a solution of NH2-<strong>[1115-74-8]Val-Ala</strong>-OH (941 mg, 5 mmol) in DMF ( 10 mL), added DIEA (1.73 mL, 10 mmol) and N-(Allyloxycarbonyloxy)succinimide (1.15 rnL, 7.5 mmol). Reaction mixture was stirred for 3 hr, quenched with water (3 mL) and stirred overnight. Solvent was removed in vacuo and the residue was diluted with HCl in water (40 mL, 0.25 M). After sonication, the precipitate was filtered off and dried thoroughly to afford 2 (600 mg, 44% yield). 1H NMR (500 MHz, DMSO-d6) delta: 12.48 (bs, 1H), 8.18 id. J= 7,0 Hz, 1H), 7, 16 id. ./ 9.4 Hz, 1H), 5.95-5.83 (m, IH), 5.28 (d, J= 15.8 Hz, 1H), 5.17 (d. J = 10.5 Hz, 1H), 4 ,47 (m, 2H), 4.18 (m, 1H). 3,87 (m, 1H). 1.94 (m, 1H), 1.26 (d, J= 7.6 Hz, 3H), 0.86 (dd, J = 14.6, 6.7 Hz, 6H). LC/MS: retention time 0.25 min. (ESI) C12H21N2O5: [M+H]+ 273; found 273.
 

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