125238-99-5

Basic information

• Product Name: FMOC-DAB(BOC)-OH
• Synonyms: N-ALPHA-(9-FLUORENYLMETHYLOXYCARBONYL)-N-GAMMA-T-BUTYLOXYCARBONYL-L-2,4-DIAMINOBUTYRIC ACID;N-ALPHA-(9-FLUORENYLMETHYLOXYCARBONYL)-N-GAMMA-TERT-BUTYLOXYCARBONYL-L-2,4-DIAMINOBUTYRIC ACID;NA-FMOC-NG-BOC-(S)-2,4-DIAMINOBUTYRIC ACID;FMOC-4-BOC-L-2,4-DIAMINOBUTYRIC ACID;FMOC-L-2,4-DIAMINOBUTYRIC ACID(BOC);FMOC-L-DAB(BOC);FMOC-L-DAB(BOC)-OH;FMOC-DAB(BOC)-OH
• CAS NO: 125238-99-5
• Molecular Formula: C₂₄H₂₈N₂O₆
• Molecular Weight: 440.49
• EINECS: 1533716-785-6
• Product Categories: Unusual amino acids;Amino Acids;amino acid
• Mol File: 125238-99-5.mol
• Article Data: 5

Chemical Properties

• Melting Point: 111-113℃
• Boiling Point: 670.9 °C at 760 mmHg
• Flash Point: 359.6 °C
• Appearance: /
• Density: 1.243 g/cm³
• Vapor Pressure: 6.47E-19mmHg at 25°C
• Refractive Index: 1.575
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 3.79±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• BRN: 6250328
• CAS DataBase Reference: FMOC-DAB(BOC)-OH(CAS DataBase Reference)
• NIST Chemistry Reference: FMOC-DAB(BOC)-OH(125238-99-5)
• EPA Substance Registry System: FMOC-DAB(BOC)-OH(125238-99-5)

Safety Data

• Hazard Codes: Xi
• WGK Germany: 3
• F: 10
• HazardClass: IRRITANT
• Hazardous Substances Data: 125238-99-5(Hazardous Substances Data)

Usage

Chemical Properties

White powder

Uses

Fmoc-Dab(Boc)-OH,

InChI:InChI=1/C24H28N2O6/c1-24(2,3)32-22(29)25-13-12-20(21(27)28)26-23(30)31-14-19-17-10-6-4-8-15(17)16-9-5-7-11-18(16)19/h4-11,19-20H,12-14H2,1-3H3,(H,25,29)(H,26,30)(H,27,28)/t20-/m0/s1

Synthetic route

di-tert-butyl dicarbonate (24424-99-5) + Nα-(9-fluorenylmethoxycarbonyl)-L-2,4-diaminobutyric acid (161420-87-7) → (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5)

Conditions	Yield
With sodium hydroxide In water; acetone at 0 - 10℃; for 4h; pH=7.5 - 8; pH-value;	86.62%
With triethylamine In water; dimethyl sulfoxide	74.2%
With sodium hydrogencarbonate In water; acetonitrile for 6h; Yield given;

(S)-(3-fluoren-9-yl-9-methoxycarbonyl)-4-[2-(tert-butyloxycarbonylamino)ethyl]-5-oxazolidinone → (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5)

Conditions	Yield
With lithium hydroxide In tetrahydrofuran at 20℃;	73%

9H-9-fluorenylmethyl (4S)-4-(3-azido-2-oxopropyl)-5-oxo-1,3-oxazolone-3-carboxylate (918428-66-7) → (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 88 percent / toluene / 0.25 h / microwave irradiation 2: 73 percent / LiOH / tetrahydrofuran / 20 °C View Scheme

Nα-Fmoc-Glu-5-oxazolidinone (159530-17-3) → (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / N-methylmorpholine; IBC-Cl; NaN3 / tetrahydrofuran / 0.5 h / -10 °C 2: 88 percent / toluene / 0.25 h / microwave irradiation 3: 73 percent / LiOH / tetrahydrofuran / 20 °C View Scheme

N2-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-glutamine (71989-20-3) + Fmoc-Ala → (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 88.9 percent / I,I-bis(trifluoroacetoxy)iodobenzene; H2O / dimethylsulfoxide / 20 h 2: 74.2 percent / triethylamine / H2O; dimethylsulfoxide View Scheme

N2-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-glutamine (71989-20-3) → (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine; bis-[(trifluoroacetoxy)iodo]benzene / 1.) CH3CN, H2O, 60 deg C, 2.) CH3CN, H2O, 60 deg C, 5 h 2: sodium hydrogencarbonate / water; acetonitrile / 6 h View Scheme

diazomethane (186581-53-3, 908094-01-9) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → Fmoc-L-Dbu(Boc)-OCH3 (125218-68-0)

Conditions	Yield
In diethyl ether for 0.166667h; Methylation;	100%

(S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + benzylamine (100-46-9) → (9H-fluoren-9-yl)methyl tert-butyl (4-(benzylamino)-4-oxobutane-1,3-diyl)(S)-dicarbamate (316152-95-1)

Conditions	Yield
With benzotriazol-1-ol; diisopropyl-carbodiimide In DMF (N,N-dimethyl-formamide); dichloromethane at 35℃;	100%
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane for 2h; Inert atmosphere;	98%
Stage #1: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With benzotriazol-1-ol; diisopropyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide for 0.0833333h; Stage #2: benzylamine In dichloromethane; N,N-dimethyl-formamide at 35℃;	98%
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In acetonitrile at 20℃; for 3h;	14.4 g
With benzotriazol-1-ol; dicyclohexyl-carbodiimide In acetonitrile at 20℃; for 2.5h;

(S)-2-amino-3-phenylpropionamide hydrochloride (65864-22-4) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → (1'S, 2S)-4-(N-Boc-amino)-N'-(1'-carbamoyl-2'-phenylethyl)-2-(N''-Fmoc-amino)butanamide (849948-77-2)

Conditions	Yield
With benzotriazol-1-ol; triethylamine; diisopropyl-carbodiimide In DMF (N,N-dimethyl-formamide); dichloromethane	100%
With benzotriazol-1-ol; triethylamine; diisopropyl-carbodiimide In dichloromethane; N,N-dimethyl-formamide for 16h;

(S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + 2-(3-chlorophenyl)ethylamine (13078-79-0) → 4-(N-Boc-amino)-N'-2-(3-chlorophenyl)ethyl-(S)-2-(N''-Fmoc-amino)butanamide (849948-71-6)

Conditions	Yield
With benzotriazol-1-ol; diisopropyl-carbodiimide In DMF (N,N-dimethyl-formamide); dichloromethane at 35℃;	100%

benzyl bromide (100-39-0) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → Fmoc-L-Dab(Boc)-OBn (668985-69-1)

Conditions	Yield
With sodium hydrogencarbonate In N,N-dimethyl-formamide at 0 - 25℃; for 26h;	98%

(S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + HCl*H-Amn-Glu(OBzl)-Gly-OAll → Fmoc-Dab(Boc)-Amn-Glu(OBzl)-Gly-OAll

Conditions	Yield
With benzotriazol-1-ol; O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl acetamide for 6h; Ambient temperature;	95.4%

N,N-bis(benzyloxycarbonyl)-1H-pyrazole-1-carboxamidine (152120-55-3) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + trifluoroacetic acid (76-05-1) → C21H24N4O6*C2HF3O2 (1573112-63-6)

Conditions	Yield
Stage #1: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With N-ethyl-N,N-diisopropylamine In dichloromethane Stage #2: With piperidine In N,N-dimethyl-formamide Stage #3: N,N-bis(benzyloxycarbonyl)-1H-pyrazole-1-carboxamidine; trifluoroacetic acid Further stages;	95.2%

morpholine 4-carboxylic acid (50881-96-4) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + (S)-3-cyclohexyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)propionic acid (135673-97-1) → C23H40N4O7 (1276031-39-0)

Conditions	Yield
Stage #1: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.5h; Stage #3: morpholine-4-carboxylic acid; (S)-3-cyclohexyl-2-(9H-fluoren-9-ylmethoxycarbonylamino)propionic acid Further stages;	95%

methyl (4S,7S,10S)-16,25-bis(2-((tert-butoxycarbonyl)amino)ethoxy)-26-methoxy-7-methyl-10-(methylamino)-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxylate + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → methyl (4S,7S,10S)-10-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-((tert-butoxycarbonyl)amino)-N-methylbutanamido)-16,25-bis(2-((tert-butoxycarbonyl)amino)ethoxy)-26-methoxy-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxylate

Conditions	Yield
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℃; for 0.5h;	95%

C49H45N3O4S3 + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → C73H71N5O9S3

Conditions	Yield
Stage #1: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With 2,4,6-trichlorobenzoyl chloride; triethylamine In tetrahydrofuran at 0℃; for 2h; Stage #2: C49H45N3O4S3 With dmap In tetrahydrofuran at 0 - 25℃; for 1h;	91%

methyl (4S,7S,10S)-16-(2-((tert-butoxycarbonyl)amino)ethoxy)-26-hydroxy-7-methyl-10-(methylamino)-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxylate + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → methyl (4S,7S,10S)-10-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-((tert-butoxycarbonyl)amino)-N-methylbutanamido)-16-(2-((tert-butoxycarbonyl)amino)ethoxy)-26-hydroxy-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxylate

Conditions	Yield
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 tetrahydrofuran at 50℃; for 12h; Inert atmosphere;	89%
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 at 20℃; for 4h; Inert atmosphere;	78%

allyl bromide (106-95-6) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → Fmoc-L-Dab(Boc)-OAllyl, Dab = 2,4-diaminobutyric acid

Conditions	Yield
With Aliquat (at)366; sodium hydrogencarbonate In dichloromethane; water at 20℃;	83%
With Aliquat 336; sodium hydrogencarbonate In dichloromethane; water at 20℃;

EB-NH2 + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → C48H48N6O12S2

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide for 24h;	80%

thymidyl acetic acid (20924-05-4) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → C26H26N4O7

Conditions	Yield
Stage #1: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With trifluoroacetic acid In dichloromethane at 45℃; for 1h; Stage #2: thymidyl acetic acid With 2,4,6-trimethyl-pyridine; 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 1-methyl-pyrrolidin-2-one for 1.5h;	80%

methyl 2'-(3'-(4-(aminomethyl)-[2,4'-bioxazol]-2'-yl)-[1,1'-biphenyl]-3-yl)-[2,4'-bioxazole]-4-carboxylate (1447274-12-5) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → methyl 2'-(3'-(4-((2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(((tert-butoxy)carbonyl)amino)butanamido)methyl)-[2,4'-bioxazol]-2'-yl)-[1,1'-biphenyl]-3-yl)-[2,4'-bioxazol]-4-carboxylate (1447274-28-3)

Conditions

Yield

Stage #1: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide for 0.0833333h; Inert atmosphere; Stage #2: methyl 2'-(3'-(4-(aminomethyl)-[2,4'-bioxazol]-2'-yl)-[1,1'-biphenyl]-3-yl)-[2,4'-bioxazole]-4-carboxylate With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;

78%

Fmoc-Leu-OH (35661-60-0) + N-Fmoc L-Phe (35661-40-6) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid → NH2-D-Dab-L-Dab-L-Dab-L-Leu-D-Phe-L-Dab-L-Dab-L-Leu-NH2

Conditions

Yield

Stage #1: Fmoc-Leu-OH 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 50℃; for 0.0833333h; Microwave irradiation; Stage #2: With piperidine In N,N-dimethyl-formamide at 75℃; for 0.1h; Microwave irradiation; Stage #3: Fmoc-Leu-OH; N-Fmoc L-Phe; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid Further stages;

77%

methyl (4S,7S,10S)-26-(benzyloxy)-10-(((benzyloxy)carbonyl)(methyl)amino)-16-(2-((tert-butoxycarbonyl)amino)ethoxy)-25-fluoro-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxylate + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → methyl (4S,7S,10S)-10-((S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-((tert-butoxycarbonyl)amino)-N-methylbutanamido)-16-(2-((tert-butoxycarbonyl)amino)ethoxy)-25-fluoro-26-hydroxy-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxylate

Conditions

Yield

Stage #1: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With 4-methyl-morpholine; 2-chloro-4,6-dimethoxy-1 ,3,5-triazine In tetrahydrofuran for 0.333333h; Stage #2: methyl (4S,7S,10S)-26-(benzyloxy)-10-(((benzyloxy)carbonyl)(methyl)amino)-16-(2-((tert-butoxycarbonyl)amino)ethoxy)-25-fluoro-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxylate In tetrahydrofuran at 20℃; for 2h;

68%

(S)-2,4-dimethyl-pent-4-enoic acid (1070774-52-5) + Fmoc-D-abrine (1070774-51-4) + N-Fmoc-O-TIPS-β-tyrosine (1070774-49-0) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → C46H69N5O8Si

Conditions	Yield
Stage #1: N-Fmoc-O-TIPS-β-tyrosine With N-ethyl-N,N-diisopropylamine In dichloromethane; N,N-dimethyl-formamide at 20℃; for 4h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.25h; Stage #3: (S)-2,4-dimethyl-pent-4-enoic acid; Fmoc-D-abrine; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid	65%

(naphth-1-yl)methylamine (118-31-0) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → 4-N-Boc-amino-(S)-2-N'-Fmoc-amino-N''-1-naphthylmethylbutanamide (369656-01-9)

Conditions	Yield
With benzotriazol-1-ol; diisopropyl-carbodiimide In DMF (N,N-dimethyl-formamide); dichloromethane at 50℃;	60%

3-hydroxymethyl-benzoic acid (3006-96-0) + acetic acid (64-19-7) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester (143824-78-6) → C17H20N4O3

Conditions

Yield

Stage #1: 3-hydroxymethyl-benzoic acid With piperidine; N-ethylmorpholine;; N-[(1H-benzotriazol-1-yl)(dimethylamino)methylene]-N-methylmethanaminium tetrafluoroborate In N,N-dimethyl-formamide for 2.08333h; Stage #2: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With 1-methyl-1H-imidazole; 1-(mesitylene-2-sulfonyl)-3-nitro-1H-1,2,4-triazole In dichloromethane for 1.08333h; Stage #3: acetic acid; 3-[(S)-2-carboxy-2-(9H-fluoren-9-ylmethoxycarbonylamino)ethyl]indole-1-carboxylic acid tert-butyl ester Further stages;

59%

4-methylhexanoic acid (1561-11-1) + Fmoc-Leu-OH (35661-60-0) + N-Fmoc L-Phe (35661-40-6) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid → C48H86N14O9

Conditions

Yield

Stage #1: Fmoc-Leu-OH 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 50℃; for 0.0833333h; Microwave irradiation; Stage #2: With piperidine In N,N-dimethyl-formamide at 75℃; for 0.1h; Microwave irradiation; Stage #3: 4-methylhexanoic acid; Fmoc-Leu-OH; N-Fmoc L-Phe; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid Further stages;

58%

tert-Butyl (3R,4S,5S)-3-methoxy-4-(N-methylamino)-5-methylheptanoate hydrochloride (120205-48-3) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → Fmoc-Dab(Boc)-Dil-OtBu

Conditions	Yield
Stage #1: tert-Butyl (3R,4S,5S)-3-methoxy-4-(N-methylamino)-5-methylheptanoate hydrochloride; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With N-ethyl-N,N-diisopropylamine In ethyl acetate at 0℃; for 0.666667h; Stage #2: With 2-chloro-1-methyl-pyridinium iodide In ethyl acetate at 0 - 20℃; for 12h;	51%

2-ethyl-N-butylamine (617-79-8) + benzyl 2-oxobut-3-enylcarbamate (1187487-23-5) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → (S)-9-fluorenylmethyl 10-(2-ethylbutyl)-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-triazaoctadecan-8-ylcarbamate (1185654-07-2)

Conditions	Yield
Stage #1: 2-ethyl-N-butylamine; benzyl 2-oxobut-3-enylcarbamate In dichloromethane at 20℃; for 0.25h; Stage #2: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With diisopropyl-carbodiimide In dichloromethane at 20℃;	46%
Stage #1: 2-ethyl-N-butylamine; benzyl 2-oxobut-3-enylcarbamate In dichloromethane at 20℃; for 0.25h; Stage #2: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With diisopropyl-carbodiimide In dichloromethane at 20℃;	46%

3-(tritylthio) propanoic acid (27144-18-9) + Fmoc-Leu-OH (35661-60-0) + N-Fmoc L-Phe (35661-40-6) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid → C44H78N14O9S

Conditions

Yield

Stage #1: Fmoc-Leu-OH 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 50℃; for 0.0833333h; Microwave irradiation; Stage #2: With piperidine In N,N-dimethyl-formamide at 75℃; for 0.1h; Microwave irradiation; Stage #3: 3-(tritylthio) propanoic acid; Fmoc-Leu-OH; N-Fmoc L-Phe; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid Further stages;

32%

benzyl 2-oxobut-3-enylcarbamate (1187487-23-5) + 2,2-Diphenylethylamine (3963-62-0) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) → (S)-9-fluorenylmethyl 10-(2,2-diphenylethyl)-2,2-dimethyl-18-phenyl-4,9,13,16-tetraoxo-3,17-dioxa-5,10,15-triazaoctadecan-8-ylcarbamate (1185653-49-9)

Conditions	Yield
Stage #1: benzyl 2-oxobut-3-enylcarbamate; 2,2-Diphenylethylamine In dichloromethane at 20℃; for 0.25h; Stage #2: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With diisopropyl-carbodiimide In dichloromethane at 20℃; Product distribution / selectivity;	31%
Stage #1: benzyl 2-oxobut-3-enylcarbamate; 2,2-Diphenylethylamine In dichloromethane at 20℃; for 0.25h; Stage #2: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With diisopropyl-carbodiimide In dichloromethane at 20℃; Product distribution / selectivity;	31%
Stage #1: benzyl 2-oxobut-3-enylcarbamate; 2,2-Diphenylethylamine In dichloromethane at 20℃; for 0.25h; Stage #2: (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid With diisopropyl-carbodiimide In dichloromethane at 20℃; Product distribution / selectivity;	31%

isooctanoic acid (929-10-2) + Fmoc-L-Dab(Dde)-OH, DDE = 1-(4,4-dimethyl-2,6-dioxocylohexylidene)ethyl + Fmoc-Thr(tBu)-OH (71989-35-0) + Fmoc-D-Phe-OH (86123-10-6) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + trifluoroacetic acid (76-05-1) + Fmoc-L-Dab-OAllyl, Dab = 2,4-diaminobutyric acid (688316-86-1) + Fmoc-D-Ser(pg)-OH → polymyxin S2 TFA salt

Conditions

Yield

Stage #1: Fmoc-L-Dab-OAllyl, Dab = 2,4-diaminobutyric acid With N-ethyl-N,N-diisopropylamine In dichloromethane for 2h; 2-chlorotrityl chloride resin; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.25h; Automated synthesizer; Stage #3: isooctanoic acid; Fmoc-L-Dab(Dde)-OH, DDE = 1-(4,4-dimethyl-2,6-dioxocylohexylidene)ethyl; Fmoc-Thr(tBu)-OH; Fmoc-D-Phe-OH; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; trifluoroacetic acid; Fmoc-D-Ser(pg)-OH Further stages;

31%

...Expand

isooctanoic acid (929-10-2) + Fmoc-L-Dab(Dde)-OH, DDE = 1-(4,4-dimethyl-2,6-dioxocylohexylidene)ethyl + Fmoc-Thr(tBu)-OH (71989-35-0) + N-(9-fluorenylmethoxycarbonyl)-D-leucine (35661-60-0, 126727-03-5, 114360-54-2) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + trifluoroacetic acid (76-05-1) + Fmoc-L-Dab-OAllyl, Dab = 2,4-diaminobutyric acid (688316-86-1) + Fmoc-D-Ser(pg)-OH → polymyxin D2 TFA salt

Conditions

Yield

Stage #1: Fmoc-L-Dab-OAllyl, Dab = 2,4-diaminobutyric acid With N-ethyl-N,N-diisopropylamine In dichloromethane for 2h; 2-chlorotrityl chloride resin; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.25h; Automated synthesizer; Stage #3: isooctanoic acid; Fmoc-L-Dab(Dde)-OH, DDE = 1-(4,4-dimethyl-2,6-dioxocylohexylidene)ethyl; Fmoc-Thr(tBu)-OH; N-(9-fluorenylmethoxycarbonyl)-D-leucine; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; trifluoroacetic acid; Fmoc-D-Ser(pg)-OH Further stages;

30%

...Expand

Fmoc-Leu-OH (35661-60-0) + N-Fmoc L-Phe (35661-40-6) + N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine (103213-32-7) + (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid (125238-99-5) + N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid → C44H79N15O9S

Conditions

Yield

Stage #1: Fmoc-Leu-OH 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 50℃; for 0.0833333h; Microwave irradiation; Stage #2: With piperidine In N,N-dimethyl-formamide at 75℃; for 0.1h; Microwave irradiation; Stage #3: Fmoc-Leu-OH; N-Fmoc L-Phe; N-(9-fluorenylmethoxycarbonyl)-S-trityl-L-cysteine; (S)-4-tert-butoxycarbonylamino-2-(9H-fluoren-9-ylmethoxycarbonylamino)butyric acid; N-α-(9-fluorenylmethyloxycarbonyl)-N-γ-tert-butyloxycarbonyl-D-2,4-diaminobutyric acid Further stages;

30%

Upstream product

• 71989-20-3 N₂-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-glutamine 
• 159530-17-3 N^α-Fmoc-Glu-5-oxazolidinone 
• 918428-66-7 9H-9-fluorenylmethyl (4S)-4-(3-azido-2-oxopropyl)-5-oxo-1,3-oxazolone-3-carboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 161420-87-7 N_α-(9-fluorenylmethoxycarbonyl)-L-2,4-diaminobutyric acid 

Downstream Products

• 1628113-77-8 octyl-D-Val-D-Dab-Gly-D-Ser-D-Trp-Ala-Dab-D-Dab-Phe-Glu-Val-D-allo-Ile-Ala-OH 
• 1628113-82-5 octyl-D-Val-D-Dab-Gly-D-Ser-D-Trp-Ser-Dab-D-Dab-Phe-Glu-Ala-D-allo-Ile-Ala-OH 
• 1628113-76-7 octyl-D-Val-D-Dab-Gly-D-Ser-D-Ala-Ser-Dab-D-Dab-Phe-Glu-Val-D-allo-Ile-Ala-OH 
• 1628113-75-6 octyl-D-Val-D-Dab-Gly-D-Ala-D-Trp-Ser-Dab-D-Dab-Phe-Glu-Val-D-allo-Ile-Ala-OH 
• 1542148-60-6 octyl-tridecaptin A₁ 
• 1628113-74-5 octyl-D-Val-D-Dab-Ala-D-Ser-D-Trp-Ser-Dab-D-Dab-Phe-Glu-Val-D-allo-Ile-Ala-OH 
• 1628113-83-6 octyl-D-Val-D-Dab-Gly-D-Ser-D-Trp-Ser-Dab-D-Dab-Phe-Glu-Val-D-Ala-Ala-OH 
• 1628113-81-4 octyl-D-Val-D-Dab-Gly-D-Ser-D-Trp-Ser-Dab-D-Dab-Phe-Ala-Val-D-allo-Ile-Ala-OH 
• 1628113-80-3 octyl-D-Val-D-Dab-Gly-D-Ser-D-Trp-Ser-Dab-D-Dab-Ala-Glu-Val-D-allo-Ile-Ala-OH 
• 161420-87-7 N_α-(9-fluorenylmethoxycarbonyl)-L-2,4-diaminobutyric acid 
• 668985-69-1 Fmoc-L-Dab(Boc)-OBn 
• 110116-75-1 H-Tyr-D-Asp[*]-Phe-A₂bu[*]-NH₂ 

Relevant articles and documents

COMPOUND FOR PREPARATION OF ANTIBODY-PAYLOAD CONJUGATE AND USE THEREOF

The present application relates to a novel linker for use in bioconjugation, comprising two or more electrophilic carbon atoms of a carbonyl group, and a click chemistry functional group and, more specifically, to a linker through which a compound, a peptide, and/or a protein can be directly and/or indirectly linked by a substitution reaction to a desired target molecule, that is, a target molecule.

Practical and efficient synthesis of orthogonally protected α-2,3-diaminopropionic acid (2,3-Dap), 2,4-diaminobutanoic acid (2,4-Dab), and their N-methylated derivatives

The synthesis of orthogonally protected Fmoc-Dap/Dab (Boc/Z/Alloc)-OH starting from Fmoc-Asp/Glu has been described. The salient features of our synthetic strategy involved formation of Fmoc-Asp/Glu-5-oxazolidinone acids, conversion of acid function to acyl azides, Curtius rearrangement, and hydrolysis of the oxazolidinone group. Copyright Taylor & Francis Group, LLC.

A new somatostatin analog with optimized ring size inhibits neointima formation induced by balloon injury in rats without altering growth hormone release

We report on the synthesis and pharmacological properties of a new series of somatostatin analogs. Two lower homologs of lysine, 2,3-diaminopropanoic acid and 2,4-diaminobutyric acid, were prepared and used for cyclization via amide formation with the side chain of aspartic or glutamic acid in place of natural cystine present in many somatostatin analogs. One resulting compound, although having low binding affinities for somatostatin receptors, displayed a strong potency in inhibiting neointima formation induced by balloon injury in rats at the dose of 100 μg·kg-1·d-1. This dissociation of the antiproliferative effect from the endocrine effect seems to indicate that myointimal growth is not related to a change in growth hormone secretion.