71989-33-8

Basic information

• Product Name: FMOC-O-tert-Butyl-L-serine
• Synonyms: N-(9-FLUORENYLMETHOXYCARBONYL)-2-TERT-BUTYL-L-SERINE;NALPHA-9-Fluorenylmethoxycarbonyl-O-tert-butyl-L-serine;FMOC-O-TERT-BUTYL-L-SERINE (FMOC-L-SER(TBU)-OH);O-tert-Butyl-N-Fmoc-L-serine;9-fluorenylmethoxycarbonyl-O-tert-butyl-L-serine;N-Fmoc-O-tert-Butyl-L-serine, Fmoc-O-tert-butyl-L-serine;N-FMOC-L-Ser (O-tert-Bu) OH;2-(9H-Fluoren-9-ylmethoxycarbonylamino)-3-[(2-methylpropan-2-yl)oxy]propanoic acid
• CAS NO: 71989-33-8
• Molecular Formula: C₂₂H₂₅NO₅
• Molecular Weight: 383.44
• EINECS: 276-260-6
• Product Categories: Fluorenes, Flurenones;Amino Acids;Serine [Ser, S];Fmoc-Amino Acids and Derivatives;Amino Acids (N-Protected);Biochemistry;Fmoc-Amino Acids;Fmoc-Amino acid series
• Mol File: 71989-33-8.mol

Chemical Properties

• Melting Point: 130.5-135.5 °C(lit.)
• Boiling Point: 510.36°C (rough estimate)
• Flash Point: 303.7 °C
• Appearance: white to light yellow crystal powder
• Density: 1.2369 (rough estimate)
• Vapor Pressure: 3.16E-14mmHg at 25°C
• Refractive Index: 24 ° (C=1, AcOEt)
• Storage Temp.: 2-8°C
• PKA: 3.44±0.10(Predicted)
• BRN: 3632013
• CAS DataBase Reference: FMOC-O-tert-Butyl-L-serine(CAS DataBase Reference)
• NIST Chemistry Reference: FMOC-O-tert-Butyl-L-serine(71989-33-8)
• EPA Substance Registry System: FMOC-O-tert-Butyl-L-serine(71989-33-8)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 24/25-36/37/39-27-26
• WGK Germany: 3
• Hazardous Substances Data: 71989-33-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Fmoc-O-tert-Butyl-L-serine is used as a key building block in the total synthesis of complex peptides and proteins. Its application is crucial for the development of novel therapeutic agents and drug candidates.
Used in Antibiotic Synthesis:
Fmoc-Ser(tBu)-OH is used as a reagent in the total synthesis of antibiotics, such as daptomycin. It enables chemoselective serine ligation, which is essential for the formation of the antibiotic's cyclic structure, contributing to its antimicrobial properties.
Used in Immunotherapy:
Fmoc-O-tert-Butyl-L-serine is used as a component in the preparation of MUC1, a T-cell helper peptide. This peptide plays a significant role in the development of immunotherapies targeting cancer cells, as it can stimulate the immune system to recognize and eliminate tumor cells.
Used in Peptide-based Drug Development:
Fmoc-Ser(tBu)-OH is utilized in the linear solid-phase peptide synthesis of proteins like ubiquitin and diubiquitin. These proteins are involved in various cellular processes, including protein degradation and cell cycle regulation, making them potential targets for the development of peptide-based drugs.
Overall, Fmoc-O-tert-Butyl-L-serine is a versatile reagent in the field of peptide synthesis, with applications spanning across pharmaceuticals, antibiotic development, immunotherapy, and peptide-based drug discovery. Its unique structure allows for the controlled synthesis of complex peptides and proteins, making it an invaluable tool in the advancement of modern medicine.

InChI:InChI=1/C22H25NO5/c1-22(2,3)28-13-19(20(24)25)23-21(26)27-12-18-16-10-6-4-8-14(16)15-9-5-7-11-17(15)18/h4-11,18-19H,12-13H2,1-3H3,(H,23,26)(H,24,25)/p-1/t19-/m0/s1

Synthetic route

Fmoc-Ser(tBu)-OMe → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
With magnesium iodide In tetrahydrofuran at 120℃; for 1h; Inert atmosphere; Microwave irradiation; Sealed tube; chemoselective reaction;	98%
With aluminum (III) chloride In ethyl acetate Reflux;	86%

N-Fmoc-L-Ser(t-But)-OEt → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
With aluminum (III) chloride In ethyl acetate Reflux;	84.8%

(S)-3-tert-Butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid tert-butyl ester (129460-16-8) → Fmoc-Ser(tBu)-OH (71989-33-8) + N-(9H-fluoren-9-ylmethoxycarbonyl)-L-serine (73724-45-5)

Conditions	Yield
With silica gel In toluene for 1.25h; Heating;	A 76% B 8%

(S)-O-tert-butylserine (18822-58-7) + 9-fluorenylmethyl N-succinimidyl carbonate (102774-86-7) → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
With triethylamine In water; acetonitrile for 1h;	75%

N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide (82911-69-1) + O-tert-Butyl-L-serine Methyl Ester p-Toluenesulfonate (132776-33-1) → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
With sodium carbonate 1.) H2O, r.t., 24 h; 2.) p-dioxane, 0 deg C to r.t., 24 h; other reagent (1. step): NaOH; Yield given. Multistep reaction;

Fmoc-Ser(but)-O-Pha (146346-72-7) → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
With acetic acid; zinc Yield given;
With magnesium; acetic acid In methanol; N,N-dimethyl-formamide at 20℃; for 75h;

Fmoc-Ser(But)-OSi(CH3)3 → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
With water In 1,4-dioxane; ethyl acetate Ambient temperature; Yield given;

(S)-O-tert-butylserine (18822-58-7) + N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide (82911-69-1) → Fmoc-Ser(tBu)-OH (71989-33-8)

(S)-3-tert-Butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid tert-butyl ester (129460-16-8) → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: i-Pr2NEt / dioxane / 1 h / Heating 2: H2O / dioxane; ethyl acetate / Ambient temperature View Scheme

N-Fmoc serine phenacyl ester (125760-26-1) → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 240 h 2: zinc, acetic acid View Scheme

N-(9H-fluoren-9-ylmethoxycarbonyl)-L-serine (73724-45-5) → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: diisopropylethylamine / ethyl acetate 2: 240 h 3: zinc, acetic acid View Scheme

Fmoc-O-t-butyl-L-serine-N-hydroxysuccinimide ester → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
With benzotriazol-1-ol; 17O-water In tetrahydrofuran at 20℃; for 96 - 120h;

(fluorenylmethoxy)carbonyl chloride (28920-43-6) + C7H15NO3*ClH (247595-36-4) → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 2h;

N-[(9-fluorenylmethoxy)carbonyl]-L-serine methyl ester (82911-78-2) → Fmoc-Ser(tBu)-OH (71989-33-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: perchloric acid / 1 h / 20 °C / Cooling with ice 2: aluminum (III) chloride / ethyl acetate / Reflux View Scheme

C104H160N10O10S (1258442-44-2) + Fmoc-Ser(tBu)-OH (71989-33-8) → C126H183N11O14S (1258442-36-2)

Conditions	Yield
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	100%

C42H37ClNO6Pol + C29H31NO5 + N-Cbz-L-Phe (1161-13-3) + N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine (35661-39-3) + O-benzyl-N-Fmoc-L-serine (122889-11-6, 83792-48-7) + Fmoc-Pro-OH (71989-31-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-methionine (71989-28-1) + Nα-FMOC-Nω-L-tosylarginine (139090-50-9, 83792-47-6) + N-(((9H-fluoren-9-yl)methoxy)carbonyl)-O-(tert-butyldimethylsilyl)-L-threonine (146346-82-9) + N-alpha-(9-fluorenylmethyloxycarbonyl)-L-aspartic acid beta-allyl ester (146982-24-3) → Z-Phe-Ala-Thr(TBS)-Met-Arg(Tos)-Tyr(Pen)-Pro-Ser(tBu)-Asp(OAll)-Ser(Bzl)-Asp(OtBu)-OH (1240360-55-7)

Conditions

Yield

Stage #1: C42H37ClNO6Pol With morpholine Automated synthesizer; solid phase reaction; Stage #2: O-benzyl-N-Fmoc-L-serine With O‑(6‑chlorobezotriazol‑1‑yl)‑N,N,N,N‑tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; 6-chloro-1-hydroxybenzotriazole In 1-methyl-pyrrolidin-2-one Automated synthesizer; solid phase reaction; Stage #3: C29H31NO5; N-Cbz-L-Phe; N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine; Fmoc-Pro-OH; Fmoc-Ser(tBu)-OH; N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-methionine; Nα-FMOC-Nω-L-tosylarginine; N-(((9H-fluoren-9-yl)methoxy)carbonyl)-O-(tert-butyldimethylsilyl)-L-threonine; N-alpha-(9-fluorenylmethyloxycarbonyl)-L-aspartic acid beta-allyl ester Further stages;

100%

...Expand

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-(tBu)Asp-OH (71989-14-5) + Fmoc-Arg(Pbf)-OH (119831-72-0) + 2-(6-isocyanatohexylaminocarbonylamino)-6-methyl-4-pyrimidinone (320393-85-9) → C36H58N16O15 (1262277-03-1)

Conditions	Yield
Stage #1: Fmoc-Ser(tBu)-OH With dmap; benzotriazol-1-ol; diisopropyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 21℃; for 24h; Stage #2: With piperidine In N,N-dimethyl-formamide at 21℃; for 0.0833333h; Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-(tBu)Asp-OH; Fmoc-Arg(Pbf)-OH; 2-(6-isocyanatohexylaminocarbonylamino)-6-methyl-4-pyrimidinone Further stages;	100%

1-decanoic acid (334-48-5) + Nα-Fmoc-Nδ-(acetyl)-Nδ-(benzoyloxy)-L-ornithine + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-Orn(Boc)-OH (109425-55-0) → DA-Lys-Ser-Orn(Ac-OH)-OH

Conditions	Yield
Stage #1: Nα-Fmoc-Nδ-(acetyl)-Nδ-(benzoyloxy)-L-ornithine With N-ethyl-N,N-diisopropylamine In dichloromethane for 1h; Stage #2: 1-decanoic acid; Fmoc-Ser(tBu)-OH; Fmoc-Orn(Boc)-OH With piperidine In N,N-dimethyl-formamide Further stages;	100%

Fmoc-Ser(tBu)-OH (71989-33-8) + tert-butyl 2-(2-(2-(2-hydroxyethoxy)ethoxy)ethoxy)acetate (518044-31-0) → FmocNH-Ser(OtBu)-O(CH2CH2O)3CH2C(O)OtBu

Conditions	Yield
With dmap In dichloromethane at 20℃; for 4h; Inert atmosphere;	100%

Fmoc-Ser(tBu)-OH (71989-33-8) → N-(9H-fluoren-9-ylmethoxycarbonyl)-L-serine (73724-45-5)

Conditions	Yield
With triethylsilane; trifluoroacetic acid In dichloromethane for 0.25h; Ambient temperature;	99%
With trifluoroacetic acid at 0℃; Kinetics; Activation energy; Thermodynamic data; Further Variations:; Temperatures; Reagents;
With trifluoroacetic acid In dichloromethane at 20℃; for 2h; Inert atmosphere;	84 mg
With hydrogenchloride In water at 20℃; for 4h; Solvent; Time;
With trifluoroacetic acid In water at 20℃; for 4h;	4.96 g

glycine ethyl ester hydrochloride (623-33-6) + Fmoc-Ser(tBu)-OH (71989-33-8) → N-fluorenylmethoxycarbonyl-O-tert-butyl-L-seryl-glycine ethyl ester (1028450-88-5)

Conditions	Yield
With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide	99%

Fmoc-Ser(tBu)-OH (71989-33-8) + (S)-allyl 2-amino-6-((tert-butoxycarbonyl)amino)hexanoate (220331-35-1) → Fmoc-Ser(tBu)-Lys(Boc)-O-allyl

Conditions	Yield
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 20℃;	99%
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran at 0 - 20℃; for 15h;	90%

Fmoc-Ser(tBu)-OH (71989-33-8) + O-t-butyl serine benzyl ester (113247-75-9) → C36H44N2O7

Conditions	Yield
With 1-[(1-(cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino)]-uronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0 - 20℃; for 2h;	99%

C7H14NO3Pol + N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine (35661-39-3) + N-Fmoc L-Phe (35661-40-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-Glu(OtBu)-OH (71989-18-9) → butyrylcholinesterase nonapeptide

Conditions

Yield

Stage #1: C7H14NO3Pol; N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine With dicyclohexyl-carbodiimide; ethyl cyanoglyoxylate-2-oxime In dichloromethane at 20℃; for 1h; Stage #2: With piperidine In N,N-dimethyl-formamide at 20℃; for 0.3h; Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine; N-Fmoc L-Phe; Fmoc-Ser(tBu)-OH; Fmoc-Glu(OtBu)-OH Further stages;

99%

Fmoc-Ser(tBu)-OH (71989-33-8) + Dimethyl-(3-methyl-2-butenyl)-sulfonium tetrafluoroborate → C27H33NO5

Conditions	Yield
Stage #1: Fmoc-Ser(tBu)-OH With sodium carbonate In dichloromethane for 0.0833333h; Stage #2: Dimethyl-(3-methyl-2-butenyl)-sulfonium tetrafluoroborate With copper(I) bromide In dichloromethane at 20℃; Inert atmosphere; regioselective reaction;	99%

Fmoc-Ser(tBu)-OH (71989-33-8) + 2,4,6-trivinylcyclotriboroxane*pyridine complex → (L)-N-Fmoc-O-tert-butyl serine vinyl ester

Conditions	Yield
With N,N'-diethylurea; copper(II) bis(trifluoromethanesulfonate); triethylamine In tetrahydrofuran at 50℃; for 16h; Chan-Lam Coupling;	99%

2-(2-(2-(3,4,5-tris(isononyloxy)benzamido)ethoxy)ethoxy)benzylalcohol + Fmoc-Ser(tBu)-OH (71989-33-8) → C67H98N2O11

Conditions	Yield
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 5℃; for 5h;	99%

Fmoc-Ser(tBu)-OH (71989-33-8) → FMOC-Ser(t-Bu)-F (130858-98-9)

Conditions	Yield
With pyridine; trifluoro-[1,3,5]triazine In dichloromethane at 20℃; for 15h;	98%
With pyridine; trifluoro-[1,3,5]triazine In dichloromethane at 20℃;	97%
With pyridine; trifluoro-[1,3,5]triazine In dichloromethane for 1.5h; Ambient temperature;	72.7%
With diethylamino-sulfur trifluoride In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;

methyl (2S)-2-amino-6-{[(benzyloxy)carbonyl]amino}hexanoate hydrochloride (27894-50-4) + Fmoc-Ser(tBu)-OH (71989-33-8) → Fmoc-Ser(tBu)-Lys(Z)-OMe (442663-72-1)

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; pH=8 - 9;	98%

Fmoc-Ser(tBu)-OH (71989-33-8) + phenylmethanethiol (100-53-8) → N-(fluoren-9-ylmethoxycarbonyl)-O-(tert-butyl)-L-serine S-benzyl ester (1259301-22-8)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; N,N-dimethyl-formamide at 20℃; for 120h; Inert atmosphere;	98%
With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 18h;	91%

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + N-Fmoc L-Phe (35661-40-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine (103213-32-7) + Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine → H2N-L-Cys(Trt)-L-Arg(Pbf)-L-Cys(Trt)-L-Phe-L-Ser(tBu)-Gly-OH trifluoroacetate

Conditions	Yield
Stage #1: N-(fluoren-9-ylmethoxycarbonyl)glycine With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.916667h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.333333h; Stage #3: N-Fmoc L-Phe; Fmoc-Ser(tBu)-OH; N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine; Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine Further stages;	98%

Fmoc-Val-OH (68858-20-8) + N-Fmoc L-Phe (35661-40-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-Ile-OH (71989-23-6) + N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine (103213-32-7) → H2N-L-Val-L-Ser(tBu)-L-Phe-L-Cys(Trt)-L-Ile-L-Cys(Trt)-OH trifluoroacetate

Conditions	Yield
Stage #1: N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine With N-ethyl-N,N-diisopropylamine In dichloromethane for 0.916667h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.333333h; Stage #3: Fmoc-Val-OH; N-Fmoc L-Phe; Fmoc-Ser(tBu)-OH; Fmoc-Ile-OH; N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine Further stages;	98%

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-Tyr(tBu)-OH (71989-38-3) + Fmoc-D(*)-OH → C29H37N7O11

Conditions	Yield
Stage #1: N-(fluoren-9-ylmethoxycarbonyl)glycine With 1-methyl-pyrrolidin-2-one; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine at 20℃; for 0.5h; Stage #2: With piperidine for 0.0833333h; Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-Ser(tBu)-OH; Fmoc-Tyr(tBu)-OH; Fmoc-D(*)-OH Further stages;	98%

C35H34N4O5 + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-(tBu)Asp-OH (71989-14-5) + acetic anhydride (108-24-7) + Fmoc-Ile-OH (71989-23-6) + Fmoc-Thr(tBu)-OH (71989-35-0) → C51H79N9O11

Conditions	Yield
Stage #1: Fmoc-Ile-OH With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h; Stage #2: With piperidine In N,N-dimethyl-formamide at 20℃; for 0.2h; Stage #3: C35H34N4O5; Fmoc-Ser(tBu)-OH; Fmoc-(tBu)Asp-OH; acetic anhydride; Fmoc-Thr(tBu)-OH Further stages;	98%

fmoc-Lys(Boc)-Wang resin + N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine (35661-39-3) + Fmoc-Pro-OH (71989-31-6) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-Tyr(tBu)-OH (71989-38-3) + Fmoc-Lys(tert-butoxycarbonyl) (71989-26-9) + Fmoc-Thr(tBu)-OH (71989-35-0) + (2S,4R)-4-tert-butoxy-1-(9H-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid → Ala-Lys-Pro-Ser-Tyr-Hyp-Hyp-Thr-Tyr-Lys (119106-85-3)

Conditions

Yield

Stage #1: fmoc-Lys(Boc)-Wang resin With piperidine In N,N-dimethyl-formamide for 0.25h; Wang resin; Stage #2: Fmoc-Tyr(tBu)-OH With O-(benzotriazol-1-yl)- N,N,N’,N’-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 1h; Wang resin; Stage #3: N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine; Fmoc-Pro-OH; Fmoc-Ser(tBu)-OH; Fmoc-Tyr(tBu)-OH; Fmoc-Lys(tert-butoxycarbonyl); Fmoc-Thr(tBu)-OH; (2S,4R)-4-tert-butoxy-1-(9H-fluoren-9-ylmethoxycarbonyl)pyrrolidine-2-carboxylic acid Further stages;

97.89%

...Expand

tert-butyl L-alaninate hydrochloride (13404-22-3) + Fmoc-Ser(tBu)-OH (71989-33-8) → O-tert-Butyl-N-(9-fluorenylmethoxycarbonyl)-L-seryl-L-alanin-tert-butylester (120173-65-1)

Conditions	Yield
With N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; triethylamine In dichloromethane for 24h;	97%

C12H19NO2 (1083074-09-2) + Fmoc-Ser(tBu)-OH (71989-33-8) → C34H42N2O6 (1083074-18-3)

Conditions	Yield
With N'-methyl polystyrene; dicyclohexyl-carbodiimide In dichloromethane at 20℃; Inert atmosphere;	97%

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + C21H43N2O4PolS + Fmoc-Arg(pbf)-OH (1364408-78-5) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-(tBu)Asp-OH (71989-14-5) → C40H74N10O13S

Conditions	Yield
Stage #1: C21H43N2O4PolS; Fmoc-Ser(tBu)-OH With 1-hydroxy-7-aza-benzotriazole; diisopropyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 1h; 2-chlorotrityl chloride resin; Stage #2: With piperidine In N,N-dimethyl-formamide Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-Arg(pbf)-OH; Fmoc-(tBu)Asp-OH Further stages;	97%

Fmoc-Ser(tBu)-OH (71989-33-8) + N(ε)-benzoyloxycarbonyl-L-lysine tert-butyl ester hydrochloride (5978-22-3) → tert-butyl-N2-(N-(((9H-fluoren-9-yl)methoxy)carbonyl)-O-(tert-butyl)-L-seryl)-N6-((benzyloxy)carbonyl)-L-lysinate

Conditions	Yield
With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide for 0.0833333h; Reagent/catalyst; Solvent; Flow reactor;	97%

methyl (L)-leucinate hydrochloride (7517-19-3) + Fmoc-Ser(tBu)-OH (71989-33-8) → N-(9-fluorenyl)methoxycarbonyl-(O-tert-butyl)-L-seryl-L-leucine methyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; pentafluorophenyl 4-nitrobenzenesulfonate; 1-hydroxybenzotriazol-hydrate In N,N-dimethyl-formamide at 20℃; for 1h;	96%

hexan-1-amine (111-26-2) + Fmoc-Ser(tBu)-OH (71989-33-8) → Fmoc-O-tert-butyl-L-serine hexylamide (918130-60-6)

Conditions	Yield
With benzotriazol-1-ol; diisopropyl-carbodiimide In dichloromethane at 25℃; for 3h;	96%

(9H-fluoren-9-yl)methyl (3-methyl-1-(1H-tetrazol-5-yl) butyl)-carbamate (954147-19-4) + Fmoc-Ser(tBu)-OH (71989-33-8) + Fmoc-Lys(tert-butoxycarbonyl) (71989-26-9) + Fmoc-L-Gln(Trt)-OH (132327-80-1) → C29H47N11O7

Conditions	Yield
Multistep reaction.;	96%

Fmoc-Ser(tBu)-OH (71989-33-8) + (S)-allyl 2-amino-3-(4-(tert-butoxy)phenyl)propanoate (267001-22-9) → Fmoc-Ser(tBu)-Tyr(tBu)-Oallyl (937077-24-2)

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 45℃;	96%

Upstream product

• 18822-58-7 (S)-O-tert-butylserine 
• 102774-86-7 9-fluorenylmethyl N-succinimidyl carbonate 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 
• 132776-33-1 O-tert-Butyl-L-serine Methyl Ester p-Toluenesulfonate 
• 129460-16-8 (S)-3-tert-Butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid tert-butyl ester 
• 73724-45-5 N-(9H-fluoren-9-ylmethoxycarbonyl)-L-serine 
• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 247595-36-4 C₇H₁₅NO₃*ClH 
• 82911-78-2 N-[(9-fluorenylmethoxy)carbonyl]-L-serine methyl ester 
• 17083-26-0 O-tert-butyl-L-serine methyl ester 
• 158000-21-6 Fmoc-O-t-butyl-L-serine-N-hydroxysuccinimide ester 
• 146346-72-7 Fmoc-Ser(bu^t)-O-Pha 
• 125760-26-1 N-Fmoc serine phenacyl ester 

Downstream Products

• 71989-34-9 Fmoc-Ser(t-Bu)-ONp 
• 113534-37-5 Fmoc-Ser(tBu)-OTDO 
• 119138-21-5 Pyr-Thr(tBu)-Ser(tBu)-Phe-Thr(tBu)-Pro-OH 
• 126771-45-7 (S)-3-tert-Butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-propionic acid 4-(2,4-dichloro-phenoxycarbonylmethoxy)-benzyl ester 
• 120792-11-2 O-tert-Butyl-N-(9-fluorenylmethoxycarbonyl)-L-seryl-O-tert-butyl-L-threonyl-N^ε-(tert-butoxycarbonyl)-L-lysyl-N^ε-(tert-butoxycarbonyl)-L-lysyl-O-tert-butyl-L-threonin-benzylester 
• 120792-12-3 O-tert-Butyl-N-(9-fluorenylmethoxycarbonyl)-L-seryl-O-tert-butyl-L-seryl-O-tert-butyl-L-threonyl-N^ε-(tert-butoxycarbonyl)-L-lysyl-N^ε-(tert-butoxycarbonyl)-L-lysyl-O-tert-butyl-L-threonin-benzylester 
• 120792-13-4 O-tert-Butyl-N-(9-fluorenylmethoxycarbonyl)-L-seryl-O-tert-butyl-L-seryl-O-tert-butyl-L-seryl-O-tert-butyl-L-threonyl-N^ε-(tert-butoxycarbonyl)-L-lysyl-N^ε-(tert-butoxycarbonyl)-L-lysyl-O-tert-butyl-L-threonin-benzylester 
• 73724-45-5 N-(9H-fluoren-9-ylmethoxycarbonyl)-L-serine 
• 176842-74-3 N-(9-fluorenylmethoxycarbonyl)-O-(tert-butyl)-L-seryl-L-proline benzyl ester 
• 105751-13-1 O-tert-butyl-N^α-(fluoren-9-ylmethoxycarbonyl)-L-serine pentafluorophenyl ester 
• 244633-33-8 Fmoc-Ser(t-Bu) 2,4,5-trichlorophenylester 
• 120081-14-3 Ac-SDKP 
• 33515-09-2 L-pyroglutamyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosylglycyl-L-leucyl-L-arginyl-L-prolylglycinamide 

Relevant articles and documents

Method for preparing Fmoc-Ser (tBu)-OH

The invention relates to a method for preparing Fmoc-Ser (tBu)-OH, and belongs to the technical field of medical intermediate chemical engineering. The technical problem to be solved by the inventionis to provide a method for preparing Fmoc-Ser (tBu)-OH. The method comprises the following steps: a, enabling Ser-OR. HCl to react with Fmoc-OSu, so as to obtain an Fmoc-Ser-OR solid; b, mixing the Fmoc-Ser-OR solid, tert-butyl acetate, perchloric acid and tert-butyl alcohol, reacting at 15-40 DEG C, regulating the pH value to 5-6, separating out a solid, filtering, washing and drying to obtain anFmoc-Ser (tBu)-OR solid; and c, hydrolysis: carrying out hydrolysis on the Fmoc-Ser (tBu)-ORsolid to obtain an Fmoc-Ser (tBu)-OH product. According to the method, the Fmoc group is introduced firstly, the racemization risk in the saponification process can be reduced, tert-butyl acetate, perchloric acid, tert-butyl alcohol and hydroxyl in Fmoc-Ser-OR are adopted for reaction when tert-butyl is introduced, operation is easy and controllable, safety is good, the obtained product is high in chiral purity and low in cost, the production steps can be effectively shortened, and the production efficiency and yield are improved; the method is suitable for modern industrial production.

Preparation method of fmoc-O-tert-butyl-L-serine

The invention discloses a preparation method of fmoc-O-tert-butyl-L-serine. The method comprises the steps that 1, L-serine and a methanol solution are added into a reaction container, and under stirring, SOCl2 is added dropwise for reflux reaction to obtain L-serine methyl ester hydrochloride; 2, the L-serine methyl ester hydrochloride is added into tert-butyl acetate, and a catalyst is added forreaction to obtain O-tert-butyl-L-serine methyl ester; 3, the O-tert-butyl-L-serine methyl ester is added into alkaline liquid for saponification reaction to obtain an O-tert-butyl-L-serine aqueous solution; 4, an organic solvent and NaCO3 are added into O-tert-butyl-L-serine, then fmoc n-hydroxysuccinimide este is added to adjust a pH value to be 8-10, and extraction separation is conducted to obtain the fmoc-O-tert-butyl-L-serine. In the preparation method, the L-serine, methanol and SOCl2 are adopted as raw materials, and through the reflux reaction, the L-serine methyl ester hydrochlorideis prepared; the reaction is carried out in liquid phases respectively, and is safe and pollution-free.

MgI2-Mediated Chemoselective Cleavage of Protecting Groups: An Alternative to Conventional Deprotection Methodologies

The scope of MgI2 as a valuable tool for quantitative and mild chemoselective cleavage of protecting groups is described here. This novel synthetic approach expands the use of protecting groups, widens the concept of orthogonality in synthetic processes, and offers a facile opportunity to release compounds from solid supports. Amazing MgI2: Protecting groups have had a tremendous positive impact on the art of biomolecule synthesis. In a context in which the use of attractive protecting groups is often limited by harsh deprotection conditions and low chemoselective flexibility, MgI2 offers, by the execution of a very simple protocol, a fresh vision with extensive perspectives.

A one-pot procedure for the preparation of N-9-fluorenylmethyloxycarbonyl- α-amino diazoketones from α-amino acids

The study describes a new "one-pot" route to the synthesis of N-9-fluorenylmethyloxycarbonyl (Fmoc) α-amino diazoketones. The procedure was tested on a series of commercially available free or side-chain protected α-amino acids employed as precursors. The conversion into the title compounds was achieved by masking and activating the α-amino acids with a single reagent, namely, 9-fluorenylmethyl chloroformate (Fmoc-Cl). The resulting N-protected mixed anhydrides were reacted with diazomethane to lead to the α-amino diazoketones, which were isolated by flash column chromatography in very good to excellent overall yields. The versatility of the procedure was verified on lipophilic α-amino acids and further demonstrated by the preparation of N-Fmoc-α-amino diazoketones also from α-amino acids containing side-chain masking groups, which are orthogonal to the Fmoc one. The results confirmed that tert-butyloxycarbonyl (Boc), tert-butyl (tBu), and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf), three acid-labile protecting groups mostly adopted in the solution and solid-phase peptide synthesis, are compatible to the adopted reaction conditions. In all cases, the formation of the corresponding C-methyl ester of the starting amino acid was not observed. Moreover, the proposed method respects the chirality of the starting α-amino acids. No racemization occurred when the procedure was applied to the synthesis of the respective N-Fmoc-protected α-amino diazoketones from l-isoleucine and l-threonine and to the preparation of a diastereomeric pair of N-Fmoc-protected dipeptidyl diazoketones.

NOVEL PEPTIDES DERIVED FROM NCAM (FGLs)

The present invention relates to novel compounds comprising at most 13 contiguous amino acid residues derived from the fibronectin type 3,I1 module of neural cell adhesion molecule (NCAM), or a variant or fragment thereof, capable of interacting with an FGFR and thereby the compounds are capable of inducing differentiation, modulating proliferation, stimulate regeneration, neuronal plasticity and/or survival of cells. Further, the present invention relates to the use of said compounds for production of a medicament for treatment of conditions and diseases, wherein NCAM and/or FGFR play a prominent role.

FLUORENE COMPOUND

Particular compounds having a fluorene skeleton are superior in broad utility and stability, as a protecting reagent for liquid phase synthesis of amino acids and/or peptides.

Derivates of Polyethylene Glycol Modified Thymosin Alpha 1

Pharmaceutical compositions that include thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol, and their pharmaceutical acceptable salts, are generally disclosed. Also, new methods used to prepare these thymosin alpha 1 peptide derivatives modified at the C-terminal of the peptide chain with polyethylene glycol are generally provided. The presently disclosed compounds and their salts can be prepared administered to humans to treat immune disease and can also be used in adjuvant treatment.

METHOD OF LABELING WITH ISOTOPE OF OXYGEN

The present invention provides methods for labeling one or two oxygen atom(s) in a carboxyl group of a carboxyl-containing compound with an oxygen isotope selected from oxygen-17 ( 17 O) or oxygen-18 ( 18 O). The methods of the present invention are characterized in that an activated ester of the carboxyl-containing compound (carboxylic acid) is reacted with H 2 17 O or H 2 18 O in the presence of an activator. In the methods of the present invention, the reaction between the activated ester of a carboxylic acid and H 2 17 O or H 2 18 O can be allowed to proceed without including drastic conditions such as strongly acidic conditions or alkaline hydrolysis because an activator is used.

A novel and efficient method for cleavage of phenacylesters by magnesium reduction with acetic acid

(Equation Presented) In the present study, we use magnesium turnings as a new deprotection reagent for the phenacyl group during orthogonal organic synthesis in the presence of other esters and sensitive protecting groups. By applying the new magnesium turnings/acetic acid deprotection method, phenacyl group can be more easily combined with other protecting groups that are not compatible with the zinc/acetic acid method.

GLP-2 compounds, formulations, and uses thereof

The present invention relates to novel human glucagon-like peptide-2 (GLP-2) peptides and human glucagon-like peptide-2 derivatives which have a protracted profile of action as well as polynucleotide constructs encoding such peptides, vectors and host cells comprising and expressing the polynucleotide, pharmaceutical compositions, uses and methods of treatment.