71989-35-0

Basic information

• Product Name: FMOC-O-tert-Butyl-L-threonine
• Synonyms: FMOC-O-TERT-BUTYL-L-THREONINE;FMOC-O-T-BUTYL-L-THREONINE;FMOC-L-THR(O-T-BUTYL);FMOC-L-THREONINE(O-T-BUTYL);FMOC-L-THREONINE (TBU);FMOC-L-THREONINE T-BUTYL ETHER;FMOC-L-THR(TBU)-OH;FMOC-THREONINE(TBU)-OH
• CAS NO: 71989-35-0
• Molecular Formula: C₂₃H₂₇NO₅
• Molecular Weight: 397.46
• EINECS: 276-261-1
• Product Categories: Fluorenes, Flurenones;Amino Acid Derivatives;Amino Acids;Threonine [Thr, T];Fmoc-Amino Acids and Derivatives;Amino Acids (N-Protected);Biochemistry;Fmoc-Amino Acids;Fmoc-Amino acid series;Pyrrolidines ,Pyrroles
• Mol File: 71989-35-0.mol
• Article Data: 14

Chemical Properties

• Melting Point: 131-134 °C
• Boiling Point: 520.91°C (rough estimate)
• Flash Point: 305.6 °C
• Appearance: White/Fine Fluffy Crystalline Powder
• Density: 1.2197 (rough estimate)
• Vapor Pressure: 2.24E-14mmHg at 25°C
• Refractive Index: 15 ° (C=1, AcOEt)
• Storage Temp.: 2-8°C
• Solubility: almost transparency in Ethylacetate
• PKA: 3.42±0.10(Predicted)
• BRN: 4581133
• CAS DataBase Reference: FMOC-O-tert-Butyl-L-threonine(CAS DataBase Reference)
• NIST Chemistry Reference: FMOC-O-tert-Butyl-L-threonine(71989-35-0)
• EPA Substance Registry System: FMOC-O-tert-Butyl-L-threonine(71989-35-0)

Safety Data

• Hazard Codes: Xi,N
• Statements: 36/37/38-50/53
• Safety Statements: 24/25-36/37/39-27-26-61-60-29/56
• RIDADR: 3077
• WGK Germany: 3
• Hazardous Substances Data: 71989-35-0(Hazardous Substances Data)

Usage

Description

Fmoc-O-tert-Butyl-L-threonine, also known as N-(9-Fluorenylmethoxycarbonyl)-O-tert-butyl-L-threonine, is a synthetic derivative of the naturally occurring amino acid L-threonine. It is characterized by the presence of a 9-fluorenylmethoxycarbonyl (Fmoc) protecting group and a tert-butyl (t-Bu) protecting group on the hydroxyl group. Fmoc-O-tert-Butyl-L-threonine is a white to light yellow crystalline powder and is commonly used in the field of organic synthesis and peptide chemistry.

Uses

Used in Peptide Synthesis:
Fmoc-O-tert-Butyl-L-threonine is used as a protected amino acid building block for the synthesis of peptides and proteins. The Fmoc group serves as a protecting group for the amino group, while the tert-butyl group protects the hydroxyl group, preventing unwanted side reactions during the assembly process. This allows for the stepwise and controlled formation of peptide bonds in solid-phase peptide synthesis.
Used in Organic Synthesis:
Fmoc-O-tert-Butyl-L-threonine can also be used as a chiral building block in organic synthesis for the preparation of various pharmaceuticals, agrochemicals, and other biologically active compounds. The presence of the L-threonine chiral center and the protecting groups make it a versatile intermediate for the synthesis of enantiomerically pure compounds.
Used in Research and Development:
Fmoc-O-tert-Butyl-L-threonine is utilized in research and development for the study of peptide synthesis methods, the development of new protecting group strategies, and the investigation of the properties and applications of protected amino acids. It can also be used as a reference compound for analytical methods and quality control in the synthesis of peptides and related compounds.

InChI:InChI=1/C23H27NO5/c1-14(29-23(2,3)4)20(21(25)26)24-22(27)28-13-19-17-11-7-5-9-15(17)16-10-6-8-12-18(16)19/h5-12,14,19-20H,13H2,1-4H3,(H,24,27)(H,25,26)/p-1/t14-,20+/m1/s1

Synthetic route

(O-tert-butyl)-L-threonine (4378-13-6) + 9-fluorenylmethyl N-succinimidyl carbonate (102774-86-7) → Fmoc-Thr(tBu)-OH (71989-35-0)

Conditions	Yield
With triethylamine In water; acetonitrile for 1h;	70%

(2S,3R)-3-tert-Butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-butyric acid 2-trimethylsilanyl-ethoxymethyl ester → Fmoc-Thr(tBu)-OH (71989-35-0)

Conditions	Yield
With magnesium bromide In dichloromethane for 3h; Ambient temperature; addition at -20 deg C, 0.5 h;	67%

N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide (82911-69-1) + O-tert-Butyl-L-threonine Methyl Ester p-Toluenesulfonate (132776-34-2) → Fmoc-Thr(tBu)-OH (71989-35-0)

Conditions	Yield
With sodium hydroxide 1.) H2O, 0 deg C, 2 h; 2.) p-dioxane, 0 deg C to r.t., 24 h; Yield given. Multistep reaction;

Fmoc-Thr(but)-O-Pha (146346-73-8) → Fmoc-Thr(tBu)-OH (71989-35-0)

Conditions	Yield
With acetic acid; zinc Yield given;

N-(9-Fluorenylmethoxycarbonyl)-O-(tert-butyl)-L-threonin-(2-phenyl-2-trimethylsilyl)ethylester (275827-11-7) → Fmoc-Thr(tBu)-OH (71989-35-0)

Conditions	Yield
With tetrabutyl ammonium fluoride In dichloromethane at 20℃; β-fragmentation;

Fmoc-Thr-OH (73731-37-0) → Fmoc-Thr(tBu)-OH (71989-35-0)

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

N-(9-fluorenylmethyloxycarbonyl)-L-threonine phenacylester (125760-27-2) → Fmoc-Thr(tBu)-OH (71989-35-0)

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

(fluorenylmethoxy)carbonyl chloride (28920-43-6) + C8H17NO3*ClH (1254943-38-8) → Fmoc-Thr(tBu)-OH (71989-35-0)

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

methanol (67-56-1) + L-threonine (72-19-5) + N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide (82911-69-1) + isobutene (115-11-7) → Fmoc-Thr(tBu)-OH (71989-35-0)

Conditions	Yield
Stage #1: methanol; L-threonine With thionyl chloride at 40 - 45℃; for 20h; Stage #2: isobutene With sulfuric acid In dichloromethane at 0 - 5℃; Stage #3: N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide Further stages;

C29H30N4O5 → Fmoc-Thr(tBu)-OH (71989-35-0) + benzotriazol-1-ol (2592-95-2)

Conditions	Yield
With water for 24h; Kinetics;

3,5-dinitrobenzoic acid (99-34-3) + Fmoc-Thr(tBu)-OH (71989-35-0) + 11-(9-fluorenylmethyloxycarbonylamino)undecanoic acid (88574-07-6) + (R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-N-trityl-succinamic acid → 11-{(2S,3R)-3-tert-Butoxy-2-[(R)-2-(3,5-dinitro-benzoylamino)-3-(trityl-carbamoyl)-propionylamino]-butyrylamino}-undecanoic acid

Conditions	Yield
Multistep reaction.;	100%

Fmoc-Thr(tBu)-OH (71989-35-0) + N-(tert-butyloxycarbonyl)-threonine benzyl ester (140422-54-4, 33662-26-9) → benzyl O-(N-(((9H-fluoren-9-yl)methoxy)carbonyl)-O-(tert-butyl)-L-threonyl)-N-(tertbutoxycarbonyl)-L-threoninate

Conditions	Yield
Stage #1: Fmoc-Thr(tBu)-OH With diisopropyl-carbodiimide In dichloromethane at 0℃; for 0.0833333h; Stage #2: N-(tert-butyloxycarbonyl)-threonine benzyl ester With dmap In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 20h;	100%
With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 3h;	80%
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 0 - 20℃;

C111H173N11O12S (1258442-45-3) + Fmoc-Thr(tBu)-OH (71989-35-0) → C134H198N12O16S (1258442-37-3)

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%

Fmoc-Thr(tBu)-OH (71989-35-0) → Fmoc-Thr-OH (73731-37-0)

Conditions	Yield
With trifluoroacetic acid In dichloromethane at 20℃; for 1h;	100%
With hydrogenchloride In water at 20℃; for 4h;

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-Val-OH (68858-20-8) + Fmoc-Leu-OH (35661-60-0) + N-Fmoc L-Phe (35661-40-6) + Fmoc-Tyr(tBu)-OH (71989-38-3) + Fmoc-Thr(tBu)-OH (71989-35-0) → H2N-Thr(tBu)-Phe-Leu-Tyr(tBu)-Val-Gly-OH

Conditions	Yield
Stage #1: Fmoc-Thr(tBu)-OH With N-ethyl-N,N-diisopropylamine In dichloromethane for 3h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.1h; Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-Val-OH; Fmoc-Leu-OH; N-Fmoc L-Phe; Fmoc-Tyr(tBu)-OH Further stages;	100%

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-Leu-OH (35661-60-0) + C36H42N2O6S + N-Fmoc L-Phe (35661-40-6) + Fmoc-Thr(tBu)-OH (71989-35-0) → C46H70N6O9S

Conditions	Yield
Stage #1: Fmoc-Thr(tBu)-OH With N-ethyl-N,N-diisopropylamine In dichloromethane for 3h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.1h; Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-Leu-OH; C36H42N2O6S; N-Fmoc L-Phe Further stages;	100%

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-Leu-OH (35661-60-0) + C36H42N2O6S + N-Fmoc L-Phe (35661-40-6) + Fmoc-Thr(tBu)-OH (71989-35-0) → C46H70N6O9S

Conditions	Yield
Stage #1: Fmoc-Leu-OH With N-ethyl-N,N-diisopropylamine In dichloromethane for 3h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.1h; Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; C36H42N2O6S; N-Fmoc L-Phe; Fmoc-Thr(tBu)-OH Further stages;	100%

C46H57ClNO5Pol + Fmoc-Thr(tBu)-OH (71989-35-0) → C69H82ClN2O9Pol

Conditions	Yield
With benzotriazol-1-ol; diisopropyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide at 20℃; for 3h; solid phase reaction;	99%

Fmoc-Thr(tBu)-Nova-TGT + C30H40N2O6 + Fmoc-(tBu)Asp-OH (71989-14-5) + Fmoc-Ile-OH (71989-23-6) + Fmoc-Thr(tBu)-OH (71989-35-0) + (S)-3-(tert-butoxycarbonyl)thiazolidine-4-carboxylic acid (63091-82-7) → C54H98N8O14S

Conditions

Yield

Stage #1: Fmoc-Thr(tBu)-Nova-TGT; Fmoc-Thr(tBu)-OH With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide Inert atmosphere; Automated synthesizer; solid phase reaction; Stage #2: With piperidine; 1,8-diazabicyclo[5.4.0]undec-7-ene In N,N-dimethyl-formamide Inert atmosphere; solid phase reaction; Stage #3: C30H40N2O6; Fmoc-(tBu)Asp-OH; Fmoc-Ile-OH; (S)-3-(tert-butoxycarbonyl)thiazolidine-4-carboxylic acid Further stages;

99%

C19H30N2O5S + Fmoc-Thr(tBu)-OH (71989-35-0) → C33H39N3O7S

Conditions	Yield
Stage #1: C19H30N2O5S With trifluoroacetic acid In dichloromethane at 0 - 20℃; for 1h; Stage #2: Fmoc-Thr(tBu)-OH With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃;	99%

C71H110FN5O8 + Fmoc-Thr(tBu)-OH (71989-35-0) → C94H135FN6O12

Conditions	Yield
With benzotriazol-1-ol; diisopropyl-carbodiimide In dichloromethane at 20℃; for 13h;	99%

Fmoc-D-Lys(Mtt)-OH (198544-94-4) + Fmoc-4FPhe-ClTrt resin + N-Fmoc L-Phe (35661-40-6) + Fmoc-Lys(tert-butoxycarbonyl) (71989-26-9) + Fmoc-Thr(tBu)-OH (71989-35-0) + Fmoc-D-Tyr(O-tBu)-OH + 1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan + Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine → DTyr-cyclo(DLys-Arg-Phe-Phe-DTrp-Lys-Thr-4FPhe) (1608155-32-3)

Conditions

Yield

Stage #1: Fmoc-4FPhe-ClTrt resin With piperidine; 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) In N,N-dimethyl-formamide for 0.5h; ClTrt resin; Stage #2: Fmoc-D-Tyr(O-tBu)-OH With piperidine; 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) In N,N-dimethyl-formamide Stage #3: Fmoc-D-Lys(Mtt)-OH; N-Fmoc L-Phe; Fmoc-Lys(tert-butoxycarbonyl); Fmoc-Thr(tBu)-OH; 1-tert-butoxycarbonyl-N-[(9-fluorenyl)methoxycarbonyl]-D-tryptophan; Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine Further stages;

98.8%

...Expand

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

Fmoc-Thr(tBu)-OH (71989-35-0) → Fmoc-Thr(t-Bu)-ol (189337-28-8)

Conditions	Yield
Stage #1: Fmoc-Thr(tBu)-OH With 4-methyl-morpholine; isobutyl chloroformate In 1,2-dimethoxyethane at -15℃; Stage #2: With sodium tetrahydroborate; water In 1,2-dimethoxyethane	97%
Stage #1: Fmoc-Thr(tBu)-OH With 1,1'-carbonyldiimidazole In tetrahydrofuran at 20℃; for 1h; Stage #2: With sodium tetrahydroborate In tetrahydrofuran; water at 0℃; for 1h;	90.3%
Stage #1: Fmoc-Thr(tBu)-OH With 4-methyl-morpholine; isobutyl chloroformate In diethylene glycol dimethyl ether at -15℃; for 0.0833333h; Stage #2: With sodium tetrahydroborate In water for 1h;
Stage #1: Fmoc-Thr(tBu)-OH With 4-methyl-morpholine; chloroformic acid ethyl ester In tetrahydrofuran at -15℃; for 0.25h; Stage #2: With sodium tetrahydroborate In tetrahydrofuran for 0.5h; Stage #3: With water In tetrahydrofuran for 0.25h;
Stage #1: Fmoc-Thr(tBu)-OH With 4-methyl-morpholine; isobutyl chloroformate In diethylene glycol dimethyl ether at -15℃; for 0.0833333h; Stage #2: With sodium tetrahydroborate In water for 1h;

Fmoc-Thr(tBu)-OH (71989-35-0) → (O-tert-butyl)-L-threonine (4378-13-6)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 50℃; for 12h;	97%
With piperidine In tetrahydrofuran for 4h;
With triethylamine In dichloromethane at 20℃; for 4h;	277 mg

C10H14N2O3S + Fmoc-Thr(tBu)-OH (71989-35-0) → C33H39N3O7S

Conditions	Yield
Stage #1: C10H14N2O3S; Fmoc-Thr(tBu)-OH With benzotriazol-1-ol; triethylamine In dichloromethane at 0℃; for 0.25h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 0 - 20℃;	97%
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 dichloromethane at 20℃; for 1.5h;	2 g

N-hydroxyphthalimide (524-38-9) + Fmoc-Thr(tBu)-OH (71989-35-0) → C31H30N2O7

Conditions	Yield
With dmap; diisopropyl-carbodiimide In dichloromethane at 0 - 20℃;	97%

(S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-methyloct-7-enoic acid + N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-Leu-OH (35661-60-0) + N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine (35661-39-3) + N-Fmoc L-Phe (35661-40-6) + Fmoc-Ile-OH (71989-23-6) + Fmoc-Tyr(tBu)-OH (71989-38-3) + Fmoc-Thr(tBu)-OH (71989-35-0) + Fmoc-Arg(Pbf)-OH (119831-72-0) + 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester (143824-78-6) → C78H117N17O14

Conditions

Yield

Stage #1: 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester With diisopropyl-carbodiimide In N,N-dimethyl-formamide at 20℃; for 2h; amide resin; Stage #2: With piperidine In N,N-dimethyl-formamide at 20℃; for 0.5h; amide resin; Stage #3: (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-2-methyloct-7-enoic acid; N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-Leu-OH; N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine; N-Fmoc L-Phe; Fmoc-Ile-OH; Fmoc-Tyr(tBu)-OH; Fmoc-Thr(tBu)-OH; Fmoc-Arg(Pbf)-OH Further stages;

96%

...Expand

N-(fluoren-9-ylmethoxycarbonyl)glycine (29022-11-5) + Fmoc-Val-OH (68858-20-8) + Fmoc-Leu-OH (35661-60-0) + N-Fmoc L-Phe (35661-40-6) + Fmoc-Tyr(tBu)-OH (71989-38-3) + Fmoc-Thr(tBu)-OH (71989-35-0) → H2N-Leu-Tyr(tBu)-Val-Gly-Thr(tBu)-Phe-OH

Conditions	Yield
Stage #1: Fmoc-Leu-OH With N-ethyl-N,N-diisopropylamine In dichloromethane for 3h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.1h; Stage #3: N-(fluoren-9-ylmethoxycarbonyl)glycine; Fmoc-Val-OH; N-Fmoc L-Phe; Fmoc-Tyr(tBu)-OH; Fmoc-Thr(tBu)-OH Further stages;	96%

N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine (35661-39-3) + Fmoc-Thr(tBu)-OH (71989-35-0) + N-tert-butoxycarbonyl-D-alloisoleucine (13139-16-7, 35264-07-4, 55721-65-8, 55780-90-0, 116194-21-9) → Boc-NH-D-allo-Ile-Ala-Thr(tBu)OH

Conditions	Yield
Stage #1: Fmoc-Thr(tBu)-OH With N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 5.5h; Inert atmosphere; Stage #2: With piperidine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 0.366667h; Inert atmosphere; Stage #3: N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine; N-tert-butoxycarbonyl-D-alloisoleucine Further stages;	96%

(R)-benzyl 2-hydroxy-4-methylpentanoate (37755-48-9) + Fmoc-Thr(tBu)-OH (71989-35-0) → benzyl (R)-2-((N-(((9H-fluoren-9-yl)methoxy)carbonyl)-O-(tert-butyl)-L-threonyl)oxy)-4-methylpentanoate

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide In dichloromethane at 20℃;	96%

1-hydroxy-pyrrolidine-2,5-dione (6066-82-6) + Fmoc-Thr(tBu)-OH (71989-35-0) → N-hydroxysuccinimyl N-(((9-fluorenylmethyl)oxy)carbonyl)-O-(tert-butyl)-L-threoninate (75530-95-9)

Conditions	Yield
With 1,3-di-tert-butylcarbodiimide In 1,4-dioxane; water at 25℃; for 16h;	95%
With dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; Esterification;

Fmoc-Thr(tBu)-OH (71989-35-0) + Benzyl bromoacetate (5437-45-6) → benzyloxycarbonylmethyl (2S,3R)-3-tertbutyloxy-2-(((9H-fluoren-9-ylmethoxy)carbonyl)amino)butanoate (1419234-23-3)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃;	95%

Fmoc-Ile-OH (71989-23-6) + Fmoc-Thr(tBu)-OH (71989-35-0) + trifluoroacetic acid (76-05-1) + 2-[[[(9H-fluoren-9-yl)methoxy]carbonylamino]methyl]thiazole-4-carboxylic acid (182120-85-0) + Nα-fluoren-9-ylmethoxycarbonyl-L-cysteine (157355-80-1) + Fmoc-D-Ile-OH → H2N-D-Ile-D-Cys(Trt)-L-Ile-L-Thr(tBu)-Gly-Thz-OH trifluoroacetate

Conditions

Yield

Stage #1: 2-[[[(9H-fluoren-9-yl)methoxy]carbonylamino]methyl]thiazole-4-carboxylic acid With N-ethyl-N,N-diisopropylamine In dichloromethane for 1.08333h; 2-chlorotrityl chloride resin; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.333333h; 2-chlorotrityl chloride resin; Stage #3: Fmoc-Ile-OH; Fmoc-Thr(tBu)-OH; trifluoroacetic acid; Nα-fluoren-9-ylmethoxycarbonyl-L-cysteine; Fmoc-D-Ile-OH Further stages;

95%

Dimethyl-(3-methyl-2-butenyl)-sulfonium tetrafluoroborate + Fmoc-Thr(tBu)-OH (71989-35-0) → C28H35NO5

Conditions	Yield
Stage #1: Fmoc-Thr(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℃; Reagent/catalyst; Inert atmosphere; regioselective reaction;	95%

1,3,5-tris[p-hydroxymethylphenoxy-octa(ethyleneglycol)oxymethyl]benzene + Fmoc-Thr(tBu)-OH (71989-35-0) → C147H201N3O42

Conditions	Yield
With pyridine; 2,6-Dichlorobenzoyl chloride In dichloromethane at 20℃;	95%

Upstream product

• 67-56-1 methanol 
• 72-19-5 L-threonine 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 
• 115-11-7 isobutene 
• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 1254943-38-8 C₈H₁₇NO₃*ClH 
• 125760-27-2 N-(9-fluorenylmethyloxycarbonyl)-L-threonine phenacylester 
• 73731-37-0 Fmoc-Thr-OH 
• 275827-11-7 N-(9-Fluorenylmethoxycarbonyl)-O-(tert-butyl)-L-threonin-(2-phenyl-2-trimethylsilyl)ethylester 
• 146346-73-8 Fmoc-Thr(bu^t)-O-Pha 
• 132776-34-2 O-tert-Butyl-L-threonine Methyl Ester p-Toluenesulfonate 
• 4378-13-6 (O-tert-butyl)-L-threonine 
• 102774-86-7 9-fluorenylmethyl N-succinimidyl carbonate 

Downstream Products

• 275827-11-7 N-(9-Fluorenylmethoxycarbonyl)-O-(tert-butyl)-L-threonin-(2-phenyl-2-trimethylsilyl)ethylester 
• 296774-21-5 FmocThr(Ot-Bu)-Hyp(Ot-Bu)-hTyr(Ot-Bu)Ot-Bu 
• 263846-91-9 C₇₈H₁₀₃N₉O₁₃ 
• 296774-68-0 C₇₅H₁₀₅N₁₁O₁₂ 
• 1092172-80-9 Abz-RRRRATCL-nY-NH₂ 
• 1092172-89-8 Abz-RRRRNHT-nY-NH₂ 
• 881913-37-7 3-tert-butoxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)-thiobutyric acid 2,4,6-trimethoxy-benzyl ester 

Relevant articles and documents

A Fmoc - Thr (tBu) - OH preparation method (by machine translation)

The invention discloses a Fmoc - Thr (tBu) - OH of the preparation method, relates to the field of chemical technology. The method comprises: methanol, thionyl chloride, Thr are mixed, the reaction produces Thr?OMe?HCl solution; to the Thr?OMe?HCl solution enters dichloromethane, and inject the isobutene, at the same time add sulfuric acid to maintain the acidic environment, reaction (tBu) Thr??OMe solution; will be Thr??OMe solution (tBu) saponification by alkali Thr?(tBu), then add Fmoc - OSu reaction to obtain the elementary product Fmoc - Thr (tBu) - OH; the taste for the Fmoc - Thr (tBu) - OH to obtain the Fmoc - Thr (tBu) - OH product. The method can effectively shorten the production steps, can improve the production efficiency and yield, is suitable for modern industrial production. (by machine translation)

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.

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.