Structure of Fmoc-D-Ser(Bzl)-OH
CAS No.: 122889-11-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Synonyms: N-[(9H-Fluoren-9-ylmethoxy)carbonyl]-O-(phenylmethyl)-D-serine
4.5
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| 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 |
| 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 |
84.86 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.74 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
4.03 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
4.04 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.82 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.98 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
3.52 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-4.74 |
| Solubility | 0.00765 mg/ml ; 0.0000183 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-5.52 |
| Solubility | 0.00127 mg/ml ; 0.00000305 mol/l |
| Class? Solubility class: Log S scale |
Moderately soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-7.5 |
| Solubility | 0.0000133 mg/ml ; 0.0000000318 mol/l |
| Class? Solubility class: Log S scale |
Poorly 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) |
Yes |
| 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) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
Yes |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
Yes |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
Yes |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.99 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 |
0.56 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<3.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
4.31 |
* 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.

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| Yield | Reaction Conditions | Operation 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). |

[ 29022-11-5 ]
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[ 223416-45-3 ]| Yield | Reaction Conditions | Operation 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. |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Steps 3 through 6 were then repeated with the following order of amino acids:Fmoc-Cys(Acm)Fmoc-Ser(Bzl)Fmoc-Gly |
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| Yield | Reaction Conditions | Operation 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. |
[ 35661-39-3 ]

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| Yield | Reaction Conditions | Operation 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. |

[ 122889-11-6 ]
| Yield | Reaction Conditions | Operation 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; |

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| Yield | Reaction Conditions | Operation 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; |
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[ 71989-23-6 ]
[ 122350-52-1 ]
| Yield | Reaction Conditions | Operation 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. |
[ 35661-60-0 ]
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[ 64-19-7 ]
[ 378247-75-7 ]

| Yield | Reaction Conditions | Operation 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. |
| Yield | Reaction Conditions | Operation 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). |

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A394173 [159610-93-2]
(S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-3-methoxypropanoic acid
Similarity: 0.94