132684-59-4

Basic information

• Product Name: FMOC-L-HOMOPHENYLALANINE
• Synonyms: (S)-2-(Fmoc-amino)-4-phenylbutyric acid, Fmoc-L-homophenylalanine;Fmoc-L-Beta-homo-Phe;FMOC-SS-HOMO-PHE-OH;Fmoc-Hphe-OH ,98%;Fmoc-HoPhe-PH;FMoc-Hph-OH FMoc-L-hoMoPhenylalanine;(S)-alpha-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]benzenebutanoic acid;(S)-N-Fmoc-homophenylalanine
• CAS NO: 132684-59-4
• Molecular Formula: C₂₅H₂₃NO₄
• Molecular Weight: 401.45
• Product Categories: Phenylalanine analogs and other aromatic alpha amino acids;Amino Acids;Unusual Amino Acids
• Mol File: 132684-59-4.mol
• Article Data: 2

Chemical Properties

• Melting Point: 141.0 to 145.0 °C
• Boiling Point: 628.284 °C at 760 mmHg
• Flash Point: 333.774 °C
• Appearance: /
• Density: 1.254
• Vapor Pressure: 1.19E-16mmHg at 25°C
• Refractive Index: 1.624
• Storage Temp.: 2-8°C
• PKA: 3.84±0.10(Predicted)
• Water Solubility: Slightly soluble in water.
• BRN: 4847669
• CAS DataBase Reference: FMOC-L-HOMOPHENYLALANINE(CAS DataBase Reference)
• NIST Chemistry Reference: FMOC-L-HOMOPHENYLALANINE(132684-59-4)
• EPA Substance Registry System: FMOC-L-HOMOPHENYLALANINE(132684-59-4)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 22-24/25-44-35-28-7-4
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 132684-59-4(Hazardous Substances Data)

Usage

Chemical Properties

White powder

Uses

It is used as an active pharmaceutical intermediate.

InChI:InChI=1/C25H23NO4/c27-24(28)23(15-14-17-8-2-1-3-9-17)26-25(29)30-16-22-20-12-6-4-10-18(20)19-11-5-7-13-21(19)22/h1-13,22-23H,14-16H2,(H,26,29)(H,27,28)/t23-/m1/s1

Synthetic route

D-homophenylalanine (943-73-7) + N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide (82911-69-1) → N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4)

Conditions	Yield
With sodium carbonate In 1,4-dioxane; water at 20℃; for 18h;

pentafluorophenyl trifloroacetate (14533-84-7) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → pentafluorophenyl L-α-[(9H-fluoren-9-ylmethoxycarbonyl)amino]benzenebutanoate (839719-69-6)

Conditions	Yield
With pyridine In N,N-dimethyl-formamide at 20℃; for 1h;	96%

(S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetic acid + (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (101555-63-9, 105751-19-7, 86069-86-5) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → (S)-N-((S)-1-amino-1-oxo-4-phenylbutan-2-yl)-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl)piperidine-2-carboxamide

Conditions

Yield

Stage #1: N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine 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 2h; Stage #2: With 4-methylpiperidin In N,N-dimethyl-formamide at 20℃; for 0.333333h; Sieber amide resin; Stage #3: (S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetic acid; (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid Further stages;

72.5%

N-Fmoc L-Phe (35661-40-6) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → C19H23N3O2

Conditions	Yield
Stage #1: N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine 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 Rink amide MBHA resin; Stage #2: With piperidine In N,N-dimethyl-formamide Rink amide MBHA resin; Stage #3: N-Fmoc L-Phe Further stages;	67%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(3-fluorophenyl)propanoic acid + 1-tert-butoxycarbonylaminocyclohexanecarboxylic acid (115951-16-1) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → 1-(1-aminocyclohexane-1-carbonyl)-4-[2S-N-[2S-3-(m-fluorophenyl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	60%

Fmoc-Leu-OH (35661-60-0) + Fmoc-Pro-OH (71989-31-6) + Fmoc-Asn-OH (71989-16-7) + Fmoc-L-Arg-OH (91000-69-0) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + trifluoroacetic acid (76-05-1) + 3-Phenylpropionic acid (501-52-0) → C46H70N14O8*C2HF3O2

Conditions	Yield
Stage #1: Fmoc-Asn-OH With benzotriazol-1-ol; diisopropyl-carbodiimide In N,N-dimethyl-formamide for 2h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.333333h; Stage #3: Fmoc-Leu-OH; Fmoc-Pro-OH; Fmoc-L-Arg-OH; N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine; trifluoroacetic acid; 3-Phenylpropionic acid Further stages;	60%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(3-fluorophenyl)propanoic acid + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(m-fluorophenyl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	54%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + Fmoc-Pro-OH (71989-31-6) + Fmoc-Trp-OH (35737-15-6) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → C27H33N7O4

Conditions	Yield
Multistep reaction;	51%

N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + Nα-(9-fluorenylmethoxycarbonyl)-D-serine-tert-butyl ether (71989-33-8, 128107-47-1) + Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine → C19H30N6O5 (1428768-33-5)

Conditions

Yield

Stage #1: Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine With benzotriazol-1-ol; diisopropyl-carbodiimide In 1-methyl-pyrrolidin-2-one; dichloromethane; N,N-dimethyl-formamide 2-chlorotrityl chloride resin; Stage #2: With piperidine In 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide for 0.25h; 2-chlorotrityl chloride resin; Stage #3: N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine; Nα-(9-fluorenylmethoxycarbonyl)-D-serine-tert-butyl ether Further stages;

51%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) + (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(3-methoxyphenyl)propanoic acid → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(m-methoxyphenyl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	46%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + Fmoc-Trp-OH (35737-15-6) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(indol-3-yl)propan-2-yl-amide]-4-phenylbutan-2-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	28%

Fmoc-Leu-OH (35661-60-0) + Fmoc-(tBu)Asp-OH (71989-14-5) + Fmoc-Glu(OtBu)-OH (71989-18-9) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + Fmoc-Gly → c[L-homoPhe-L-homoPhe-L-Asp-L-Glu-Gly-L-Leu-L-Glu-L-Glu]-NH2

Conditions	Yield
Multistep reaction.;	17%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) + Fmoc-β-(3-benzothienyl)-L-alanine → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(benzo[b]thiophen-3-yl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	16%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) + N-[(9-fluorenyl)methoxycarbonyl]-4-chloro-L-phenylalanine → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(p-chlorophenyl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	15%

D-homophenylalanine (943-73-7) + N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide (82911-69-1) → N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4)

Conditions	Yield
With sodium carbonate In 1,4-dioxane; water at 20℃; for 18h;

pentafluorophenyl trifloroacetate (14533-84-7) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → pentafluorophenyl L-α-[(9H-fluoren-9-ylmethoxycarbonyl)amino]benzenebutanoate (839719-69-6)

Conditions	Yield
With pyridine In N,N-dimethyl-formamide at 20℃; for 1h;	96%

(S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetic acid + (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid (101555-63-9, 105751-19-7, 86069-86-5) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → (S)-N-((S)-1-amino-1-oxo-4-phenylbutan-2-yl)-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl)piperidine-2-carboxamide

Conditions

Yield

Stage #1: N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine 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 2h; Stage #2: With 4-methylpiperidin In N,N-dimethyl-formamide at 20℃; for 0.333333h; Sieber amide resin; Stage #3: (S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetic acid; (S)-1-(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid Further stages;

72.5%

N-Fmoc L-Phe (35661-40-6) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → C19H23N3O2

Conditions	Yield
Stage #1: N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine 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 Rink amide MBHA resin; Stage #2: With piperidine In N,N-dimethyl-formamide Rink amide MBHA resin; Stage #3: N-Fmoc L-Phe Further stages;	67%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(3-fluorophenyl)propanoic acid + 1-tert-butoxycarbonylaminocyclohexanecarboxylic acid (115951-16-1) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → 1-(1-aminocyclohexane-1-carbonyl)-4-[2S-N-[2S-3-(m-fluorophenyl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	60%

Fmoc-Leu-OH (35661-60-0) + Fmoc-Pro-OH (71989-31-6) + Fmoc-Asn-OH (71989-16-7) + Fmoc-L-Arg-OH (91000-69-0) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + trifluoroacetic acid (76-05-1) + 3-Phenylpropionic acid (501-52-0) → C46H70N14O8*C2HF3O2

Conditions	Yield
Stage #1: Fmoc-Asn-OH With benzotriazol-1-ol; diisopropyl-carbodiimide In N,N-dimethyl-formamide for 2h; Stage #2: With piperidine In N,N-dimethyl-formamide for 0.333333h; Stage #3: Fmoc-Leu-OH; Fmoc-Pro-OH; Fmoc-L-Arg-OH; N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine; trifluoroacetic acid; 3-Phenylpropionic acid Further stages;	60%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(3-fluorophenyl)propanoic acid + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(m-fluorophenyl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	54%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + Fmoc-Pro-OH (71989-31-6) + Fmoc-Trp-OH (35737-15-6) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) → C27H33N7O4

Conditions	Yield
Multistep reaction;	51%

N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + Nα-(9-fluorenylmethoxycarbonyl)-D-serine-tert-butyl ether (71989-33-8, 128107-47-1) + Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine → C19H30N6O5 (1428768-33-5)

Conditions

Yield

Stage #1: Nα-(9-fluorenylmethyloxycarbonyl)-Nγ-2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl-L-arginine With benzotriazol-1-ol; diisopropyl-carbodiimide In 1-methyl-pyrrolidin-2-one; dichloromethane; N,N-dimethyl-formamide 2-chlorotrityl chloride resin; Stage #2: With piperidine In 1-methyl-pyrrolidin-2-one; N,N-dimethyl-formamide for 0.25h; 2-chlorotrityl chloride resin; Stage #3: N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine; Nα-(9-fluorenylmethoxycarbonyl)-D-serine-tert-butyl ether Further stages;

51%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) + (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(3-methoxyphenyl)propanoic acid → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(m-methoxyphenyl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	46%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + Fmoc-Trp-OH (35737-15-6) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(indol-3-yl)propan-2-yl-amide]-4-phenylbutan-2-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	28%

Fmoc-Leu-OH (35661-60-0) + Fmoc-(tBu)Asp-OH (71989-14-5) + Fmoc-Glu(OtBu)-OH (71989-18-9) + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + Fmoc-Gly → c[L-homoPhe-L-homoPhe-L-Asp-L-Glu-Gly-L-Leu-L-Glu-L-Glu]-NH2

Conditions	Yield
Multistep reaction.;	17%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) + Fmoc-β-(3-benzothienyl)-L-alanine → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(benzo[b]thiophen-3-yl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	16%

N'-[(9H-fluoren-9-ylmethoxy)carbonyl]-1H-imidazole-1-carbohydrazide + N-(fluorenyl-9-methoxycarbonyl)-L-homophenylalanine (132684-59-4) + (S)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)butanoic acid (135112-27-5) + N-[(9-fluorenyl)methoxycarbonyl]-4-chloro-L-phenylalanine → 1-(2S-2-aminobutanoyl)-4-[2S-N-[2S-3-(p-chlorophenyl)propan-2-yl-amide]-4-phenylbutan-2-yl-amide]semicarbazide

Conditions	Yield
Multistep reaction;	15%

Upstream product

• 28920-43-6 (fluorenylmethoxy)carbonyl chloride 
• 82795-51-5 D-homophenylalanine 
• 943-73-7 D-homophenylalanine 
• 82911-69-1 N-(9H-fluoren-2-ylmethoxycarbonyloxy)succinimide 

Relevant articles and documents

Single Amino-Acid Based Self-Assembled Biomaterials with Potent Antimicrobial Activity

The design and development of soft biomaterials based on amino acid and short-peptide have gained much attention due to their potent biomedical applications. A slight alteration in the side-chain of single amino acid in a peptide or protein sequence has a huge impact on the structure and function. Phenylalanine is one of the most studied amino acids, which contains an aromatic phenyl group connected through a flexible ?CH2? unit. In this work, we have examined whether flexibility and aromatic functionality of phenylalanine (Phe) are important in gel formation of model gelator Fmoc-Phe-OH or not. To examine this hypothesis, we synthesized Fmoc-derivatives of three analogues unnatural amino acids including cyclohexylalanine, phenylglycine, and homophenylalanine; which are slightly varied from Phe. Interestingly, all these three new analogues formed hydrogels in phosphate buffer at pH 7.0 having different gelation efficacy and kinetics. This study suggests that the presence of aromatic side-chain and flexibility are not mandatory for the gelation of this model gelator. Newly synthesized unnatural amino acid derivatives have also exhibited promising antimicrobial activity towards gram-positive bacteria by inhibiting cellular oxygen consumption. We further determined the biocompatibility of these amino acid derivatives by using a hemolysis assay on human blood cells. Overall studies described the development of single amino acid-based new injectable biomaterials with improved antimicrobial activity by the slight alteration in the side-chain of amino acid.