Structure of Z-Ala-OSu
CAS No.: 3401-36-3
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| CAS No. : | 3401-36-3 |
| Formula : | C15H16N2O6 |
| M.W : | 320.30 |
| SMILES Code : | O=C(OCC1=CC=CC=C1)N[C@@H](C)C(ON2C(CCC2=O)=O)=O |
| English Name : | 2,5-Dioxopyrrolidin-1-yl ((benzyloxy)carbonyl)-L-alaninate |
| MDL No. : | MFCD00053548 |
| InChI Key : | OFIYNISEFIEQBC-JTQLQIEISA-N |
| Pubchem ID : | 837751 |
| Num. heavy atoms | 23 |
| Num. arom. heavy atoms | 6 |
| Fraction Csp3 | 0.33 |
| Num. rotatable bonds | 8 |
| Num. H-bond acceptors | 6.0 |
| Num. H-bond donors | 1.0 |
| Molar Refractivity | 80.72 |
| TPSA ? Topological Polar Surface Area: Calculated from |
102.01 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.83 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.87 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.38 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
0.89 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.69 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.93 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-2.04 |
| Solubility | 2.93 mg/ml ; 0.00914 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-2.6 |
| Solubility | 0.812 mg/ml ; 0.00253 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.87 |
| Solubility | 0.432 mg/ml ; 0.00135 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| 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) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
No |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-7.64 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
1.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
3.53 |
* 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.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With pyridine In acetonitrile for 5h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With potassium <i>tert</i>-butylate 1) THF, -50 deg C, 10 min, 2) THF, -30 to -20 deg C, 30 min; Yield given. Multistep reaction; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With hydrogenchloride; triethylamine In 1,2-dimethoxyethane; water | 5.A (A) (A) The Preparation of the Starting Material N-Benzyloxycarbonyl-L-alanyl-L-proline 289 g (0.903 mol) of N-benzyloxycarbonyl-L-alanine N-hydroxysuccinimide ester were dissolved in 1800 ml of 1,2-dimethoxyethane and to this solution was added a solution of 103.98 g (0.903 mol) of L-proline in 1350 ml of water followed by 267 ml (1.8 mol) of triethylamine. The mixture was stirred for 16 hours at room temperature and then the dimethoxyethane was removed by evaporation. The aqueous solution was then extracted twice with 300 ml of ethyl acetate each time and the organic layers were discarded. The remaining solution was acidified to pH 1-2 using concentrated hydrochloric acid and extracted twice with 900 ml of ethyl acetate each time. The organic layers were combined and washed twice with 400 ml of water each time, then dried over sodium sulphate, filtered and evaporated to an oil. On trituration with 1600 ml of ether, the product crystallized out and was filtered off, washed with ether and dried to yield 193.8 g of N-benzyloxycarbonyl-L-alanyl-L-proline of melting point 124°-125° C. A second crop of 27.6 g (melting point 123°-124° C.) was obtained by evaporation of the mother liquors, trituration with 300 ml of ether and storage at 4° C. for 1 hour; total yield 77%; [α]D20 =-91.2° (c=1.03% in methanol). Analysis for C16 H20 O5 N2 (320.35) Calculated: C: 60.00; H: 6.29; N: 8.74. Found: C: 59.91; H: 6.40; N: 8.85. | |
| With hydrogenchloride; triethylamine In 1,2-dimethoxyethane; water | 3.A EXAMPLE 3 (A) The preparation of the starting material: N-Benzyloxycarbonyl-L-alanyl-L-proline 289 g (0.903 mol) of N-benzyloxycarbonyl-L-alanine N-hydroxysuccinimide ester were dissolved in 1800 ml of 1,2-dimethoxyethane and to this solution was added a solution of 103.98 g (0.903 mol) of L-proline in 1350 ml of water followed by 267 ml (1.8 mol) of triethylamine. The mixture was stirred for 16 hours at room temperature and then the dimethoxyethane was removed by evaporation. The aqueous solution was then extracted twice with 300 ml of ethyl acetate each time and the organic layers were discarded. The remaining solution was acidified to pH 1-2 using concentrated hydrochloric acid and extracted twice with 900 ml of ethyl acetate each time. The organic layers were combined and washed twice with 400 ml of water each time, then dried over sodium sulphate, filtered and evaporated to an oil. On trituration with 1600 ml of ether, the product crystallized out and was filtered off, washed with ether and dried to yield 193.8 g of N-benzyloxycarbonyl-L-alanyl-L-proline of melting point 124°-125° C. A second crop of 27.6 g (melting point 123°-124° C.) was obtained by evaporation of the mother liquors, trituration with 300 ml of ether and storage at 4° C. for 1 hour; total yield 77%; [α]D20 =-91.2° (c=1.03% in methanol). Analysis for C16 H20 O5 N2 (320.35): Calculated: C: 60.00; H: 6.29; N: 8.74. Found: C: 59.91; H: 6.40; N: 8.85. | |
| Stage #1: <i>L</i>-proline With tetra(n-butyl)ammonium hydroxide; potassium carbonate In 1,4-dioxane for 0.25h; Stage #2: (N-benzyloxycarbonyl)-L-alanine N-hydroxysuccinimide ester In 1,4-dioxane for 10h; | General procedure: N-Protected dipeptide carbonitrileswere used in the present work both as such and asprecursors for the synthesis of other compounds understudy. The general procedure for the synthesis of thesecompounds is depicted in Fig. 5. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In chloroform at 20℃; for 1h; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 800.0 mg | With triethylamine In N,N-dimethyl-formamide at 0 - 20℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| With triethylamine In tetrahydrofuran; water | P.A.1.1 1. 1. Preparation of Z-Ala-Gln-OH To a solution of 4.80 g of Z-Ala-OSu in 60 ml of tetrahydrofuran was added a solution of 2.19 g of H-Gln-OH in 40 ml of water and 2.10 ml of triethylamine and the mixture was stirred at a room temperature for 20 hours. Tetrahydrofuran and water were removed by distillation and the residue thus obtained was extracted with n-butanol. The n-butanol extract was washed with a 2%-acetic acid and butanol was removed by distillation. The precipitated substance thus obtained was collected by filtration and reprecipitated with methanol-ethyl acetate to obtain 3.87 g of Z-Ala-Gln-OH. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| In dichloromethane at 0℃; for 12h; |

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