584-85-0

Basic information

• Product Name: L-Anserine
• Synonyms: L-Anserine;N-beta-alanyl-3-methyl-L-histidine;2-(3-aminopropanoylamino)-3-(3-methylimidazol-4-yl)-propanoic acid;Nα-β-Alanyl-1-dehydro-3-methyl-L-histidine;L-N-beta-Alanyl-3-methylhistidine;(S)-2-(4-Aminobutanamido)-3-(1-methyl-1H-imidazol-5-yl)propanoic acid;H-β-Ala-His(3-Me)-OH
• CAS NO: 584-85-0
• Molecular Formula: C₁₀H₁₆N₄O₃
• Molecular Weight: 240.25904
• EINECS: 209-545-0
• Product Categories: Chiral heterocyclic compounds
• Mol File: 584-85-0.mol
• Article Data: 8

Chemical Properties

• Melting Point: 268℃ (decomposition)
• Boiling Point: 611.3 °C at 760 mmHg
• Flash Point: 323.5 °C
• Appearance: /
• Density: 1.38 g/cm³
• Vapor Pressure: 8.52E-16mmHg at 25°C
• Refractive Index: 1.615
• Storage Temp.: 2-8°C(protect from light)
• Solubility: Methanol (Slightly, Heated), Water (Slightly)
• PKA: 3.02±0.10(Predicted)
• CAS DataBase Reference: L-Anserine(CAS DataBase Reference)
• NIST Chemistry Reference: L-Anserine(584-85-0)
• EPA Substance Registry System: L-Anserine(584-85-0)

Safety Data

• Hazardous Substances Data: 584-85-0(Hazardous Substances Data)

Usage

Purification Methods

Crystallise anserine from aqueous EtOH. It is hygroscopic and is best stored as the nitrate salt (see below). Purify it by shaking the nitrate salt with Dowex 3 (x4 free base) and washing with H2O, evaporating the filtrate and removing H2O by 3 distillations with 10mL of propan-2-ol. Dissolve the crystals in MeOH and add H2O dropwise until one phase is obtained and cool. Dry the crystals at 60o over P2O5 in a vacuum. The picrate has m 145o (from H2O). [Rinderknecht et al. J Org Chem 29 1968 1964, Beilstein 25 II 408, 25 IV 4383.]

InChI:InChI=1/C10H16N4O3/c1-14-6-12-5-7(14)4-8(10(16)17)13-9(15)2-3-11/h5-6,8H,2-4,11H2,1H3,(H,13,15)(H,16,17)/t8-/m0/s1

Synthetic route

C15H24N4O5 → L-anserine (584-85-0)

Conditions	Yield
With hydrogenchloride In water at 20 - 50℃; for 4h;	97%
With hydrogenchloride In water at 40 - 50℃; for 8h;	5.1 g

C16H20N4O3 → L-anserine (584-85-0)

Conditions	Yield
With sodium hydrogencarbonate at 20 - 30℃; for 8h;	95%

C25H28N4O5 → L-anserine (584-85-0)

Conditions	Yield
With ammonium formate In ethanol at 70 - 80℃; for 12h; Solvent; Reagent/catalyst; Temperature;	95%

C12H20N4O3 → L-anserine (584-85-0)

Conditions	Yield
With potassium hydroxide at 20 - 30℃; for 8h;	93%

β-alanyl-3-methyl-L-histidine methyl ester (1018683-10-7) → L-anserine (584-85-0)

Conditions	Yield
With potassium hydroxide at 20 - 30℃; for 8h;	92%

C14H24N4O3 → L-anserine (584-85-0)

Conditions	Yield
With potassium hydroxide at 20 - 30℃; for 8h;	91%

C13H22N4O3 → L-anserine (584-85-0)

Conditions	Yield
With potassium carbonate at 20 - 30℃; for 8h;	90.5%

C17H22N4O3 → L-anserine (584-85-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen at 20 - 30℃; for 2h;	90%
With palladium 10% on activated carbon; hydrogen at 20 - 30℃; for 2h;	4.9 g

C18H24N4O4 → L-anserine (584-85-0)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen at 20 - 30℃; for 2h;	90%

phthalyl-L-anserine methylester (848572-83-8) → L-anserine (584-85-0)

Conditions	Yield
With hydrogenchloride; water; hydrazine for 5h; Heating / reflux;	73.8%

N(α)-(3-((tert-butoxycarbonyl)amino)propylcarbonyl)-N(τ)-methyl-L-histidine methyl ester (952739-81-0) → L-anserine (584-85-0)

Conditions	Yield
Stage #1: N(α)-(3-((tert-butoxycarbonyl)amino)propylcarbonyl)-N(τ)-methyl-L-histidine methyl ester With sodium hydroxide In methanol; water at 20℃; for 16h; pH=> 11; Stage #2: With hydrogenchloride In methanol; water for 15h; pH=< 3;	67%
With sodium hydroxide at 20℃;
Multi-step reaction with 2 steps 1: sodium hydroxide; water / methanol / 6 h / 20 - 30 °C 2: hydrogenchloride / water / 4 h / 20 - 50 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride / methanol; water / 4 h / 20 - 40 °C 2: potassium hydroxide / 8 h / 20 - 30 °C View Scheme

benzyl N-[2-(hydrazinecarbonyl)ethyl]carbamate (21855-66-3) → L-anserine (584-85-0)

Conditions	Yield
With hydrogenchloride; water; acetic acid; sodium nitrite Umsetzen des erhaltenen Azids mit 3-Methyl-L-histidin-methylester,anschliessendes Behandeln mit wss.NaOH und Hydrieren an Palladium in wss.H2SO4;

3-methyl-L-histidine (368-16-1) + 3-amino propanoic acid (107-95-9) → L-anserine (584-85-0)

Conditions	Yield
ueber die enzymatische Synthese;

3-methylhistidine (368-16-1, 7212-31-9, 13146-97-9) + 3-amino propanoic acid (107-95-9) → L-anserine (584-85-0)

Conditions	Yield
ueber die enzymatische Synthese;

2-(3-tert-butoxycarbonylaminopropionylamino)-3-(1H-imidazol-4-yl)propionic acid methyl ester (82361-55-5) → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 98 percent / Et3N / benzene / 1 h / Heating 2: tetrahydrofuran / 1 h / Heating 3: 18.7 g / AgOAc / acetic acid; H2O / 0.08 h 4: aq. NaOH / 20 °C View Scheme

2-(3-tert-butoxycarbonylaminopropionylamino)-3-(1-trityl-1H-imidazol-4-yl)propionic acid methyl ester (952739-80-9) → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrahydrofuran / 1 h / Heating 2: 18.7 g / AgOAc / acetic acid; H2O / 0.08 h 3: aq. NaOH / 20 °C View Scheme

C35H41N4O5(1+)*I(1-) → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 18.7 g / AgOAc / acetic acid; H2O / 0.08 h 2: aq. NaOH / 20 °C View Scheme

l-histidine methyl ester dihydrochloride (4467-54-3, 5619-10-3, 7389-87-9, 18684-16-7, 22888-60-4, 32381-17-2, 92742-29-5, 100009-20-9) → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 99 percent / N'-(3-dimethylaminopropyl)-N-ethylcarbodiimide; Et3N / CH2Cl2 / 24 h / 20 °C 2: 98 percent / Et3N / benzene / 1 h / Heating 3: tetrahydrofuran / 1 h / Heating 4: 18.7 g / AgOAc / acetic acid; H2O / 0.08 h 5: aq. NaOH / 20 °C View Scheme

(S)-methyl 2-amino-3-(1-methyl-1H-imidazol-5-yl)propanoate (72244-50-9) → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 25 h / 20 °C / Inert atmosphere 2.1: sodium hydroxide / methanol; water / 16 h / 20 °C / pH > 11 2.2: 15 h / pH < 3 View Scheme
Multi-step reaction with 3 steps 1: triethylamine / acetonitrile / 4 h / 20 - 30 °C 2: sodium hydroxide; water / methanol / 6 h / 20 - 30 °C 3: hydrogenchloride / water / 4 h / 20 - 50 °C View Scheme
Multi-step reaction with 3 steps 1: triethylamine / acetonitrile / 4 h / 20 - 30 °C 2: hydrogenchloride / methanol; water / 4 h / 20 - 40 °C 3: potassium hydroxide / 8 h / 20 - 30 °C View Scheme

3-methyl-3H-imidazole-4-carboxaldehyde trifluoromethanesulfonate → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: N,N,N',N'-tetramethylguanidine / tetrahydrofuran / 25 h / 0 - 20 °C 2.1: (-)-1,2-bis-((2R,5R)-2,5-diethylphospholano)benzene(cyclooctadiene) rhodium(I) trifluoromethanesulfonate; hydrogen / 2,2,2-trifluoroethanol / 10 h / 50 °C / 15514.9 Torr 3.1: hydrogen; palladium(II) hydroxide / methanol / 3 h / 20 °C 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 25 h / 20 °C / Inert atmosphere 5.1: sodium hydroxide / methanol; water / 16 h / 20 °C / pH > 11 5.2: 15 h / pH < 3 View Scheme
Multi-step reaction with 5 steps 1.1: N,N,N',N'-tetramethylguanidine / tetrahydrofuran / 25 h / 0 - 20 °C 2.1: (-)-1,2-bis-((2R,5R)-2,5-diethylphospholano)benzene(cyclooctadiene) rhodium(I) trifluoromethanesulfonate; hydrogen / methanol / 120 °C / 80160.1 Torr 3.1: hydrogen; palladium(II) hydroxide / methanol / 3 h / 20 °C 4.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 25 h / 20 °C / Inert atmosphere 5.1: sodium hydroxide / methanol; water / 16 h / 20 °C / pH > 11 5.2: 15 h / pH < 3 View Scheme

(Z)-methyl 2-(benzyloxycarbonylamino)-3-(1-methyl-1H-imidazol-5-yl)acrylate → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: (-)-1,2-bis-((2R,5R)-2,5-diethylphospholano)benzene(cyclooctadiene) rhodium(I) trifluoromethanesulfonate; hydrogen / methanol / 120 °C / 80160.1 Torr 2.1: hydrogen; palladium(II) hydroxide / methanol / 3 h / 20 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 25 h / 20 °C / Inert atmosphere 4.1: sodium hydroxide / methanol; water / 16 h / 20 °C / pH > 11 4.2: 15 h / pH < 3 View Scheme
Multi-step reaction with 4 steps 1.1: (-)-1,2-bis-((2R,5R)-2,5-diethylphospholano)benzene(cyclooctadiene) rhodium(I) trifluoromethanesulfonate; hydrogen / 2,2,2-trifluoroethanol / 10 h / 50 °C / 15514.9 Torr 2.1: hydrogen; palladium(II) hydroxide / methanol / 3 h / 20 °C 3.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 25 h / 20 °C / Inert atmosphere 4.1: sodium hydroxide / methanol; water / 16 h / 20 °C / pH > 11 4.2: 15 h / pH < 3 View Scheme

(S)-methyl 2-(benzyloxycarbonylamino)-3-(1-methyl-1H-imidazol-5-yl)propanoate → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogen; palladium(II) hydroxide / methanol / 3 h / 20 °C 2.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine / dichloromethane / 25 h / 20 °C / Inert atmosphere 3.1: sodium hydroxide / methanol; water / 16 h / 20 °C / pH > 11 3.2: 15 h / pH < 3 View Scheme

N(τ)-methyl-L-histidine benzyl ester → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium carbonate / tetrahydrofuran / 6 h / 20 - 30 °C 2: hydrogenchloride / methanol; water / 8 h / 20 - 50 °C 3: palladium 10% on activated carbon; hydrogen / 2 h / 20 - 30 °C View Scheme
Multi-step reaction with 3 steps 1: sodium carbonate / tetrahydrofuran / 6 h / 20 - 30 °C 2: palladium 10% on activated carbon; hydrogen / methanol; water / 6 h / 20 - 30 °C 3: hydrogenchloride / water / 4 h / 20 - 50 °C View Scheme
Multi-step reaction with 3 steps 1: sodium carbonate / tetrahydrofuran / 6 h / 20 - 30 °C 2: hydrogenchloride / methanol; water / 8 h / 40 - 50 °C 3: palladium 10% on activated carbon; hydrogen / 2 h / 20 - 30 °C View Scheme
Multi-step reaction with 3 steps 1: sodium carbonate / tetrahydrofuran / 6 h / 20 - 30 °C 2: palladium 10% on activated carbon; hydrogen / methanol; water / 12 h / 20 - 30 °C 3: hydrogenchloride / water / 8 h / 40 - 50 °C View Scheme

N(α)-(3-((tert-butoxycarbonyl)amino)propylcarbonyl)-N(τ)-methyl-L-histidine benzyl ester → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / methanol; water / 8 h / 20 - 50 °C 2: palladium 10% on activated carbon; hydrogen / 2 h / 20 - 30 °C View Scheme
Multi-step reaction with 2 steps 1: hydrogenchloride / methanol; water / 8 h / 40 - 50 °C 2: palladium 10% on activated carbon; hydrogen / 2 h / 20 - 30 °C View Scheme

N(τ)-methyl-L-histidine isopropyl ester → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydrogencarbonate / toluene / 8 h / 20 - 30 °C 2: hydrogenchloride / water; toluene / 4 h / 30 - 50 °C 3: potassium carbonate / 8 h / 20 - 30 °C View Scheme
Multi-step reaction with 3 steps 1: potassium hydrogencarbonate / toluene / 8 h / 20 - 30 °C 2: formic acid / methanol; water / 6 h / 30 °C 3: hydrogenchloride / water / 4 h / 20 - 50 °C View Scheme

C18H30N4O5 → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water; toluene / 4 h / 30 - 50 °C 2: potassium carbonate / 8 h / 20 - 30 °C View Scheme
Multi-step reaction with 2 steps 1: formic acid / methanol; water / 6 h / 30 °C 2: hydrogenchloride / water / 4 h / 20 - 50 °C View Scheme

N(τ)-methyl-L-histidine phenyl ester → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium hydrogencarbonate / toluene / 4 h / 20 - 30 °C 2: potassium hydrogencarbonate / tetrahydrofuran / 8 h / 20 - 30 °C 3: hydrogenchloride / water / 4 h / 20 - 50 °C View Scheme
Multi-step reaction with 3 steps 1: potassium hydrogencarbonate / toluene / 4 h / 20 - 30 °C 2: hydrogenchloride / water; tetrahydrofuran / 4 h / 20 - 50 °C 3: sodium hydrogencarbonate / 8 h / 20 - 30 °C View Scheme

N(α)-(3-((tert-butoxycarbonyl)amino)propylcarbonyl)-N(τ)-methyl-L-histidine phenyl ester → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrogenchloride / water; tetrahydrofuran / 4 h / 20 - 50 °C 2: sodium hydrogencarbonate / 8 h / 20 - 30 °C View Scheme
Multi-step reaction with 2 steps 1: potassium hydrogencarbonate / tetrahydrofuran / 8 h / 20 - 30 °C 2: hydrogenchloride / water / 4 h / 20 - 50 °C View Scheme

N(τ)-methyl-L-histidine ethyl ester → L-anserine (584-85-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / N,N-dimethyl-formamide / 4 h / 20 - 30 °C 2: hydrogenchloride / water; ethanol / 4 h / 20 - 50 °C 3: potassium hydroxide / 8 h / 20 - 30 °C View Scheme
Multi-step reaction with 3 steps 1: sodium hydrogencarbonate / N,N-dimethyl-formamide / 4 h / 20 - 30 °C 2: sodium carbonate / 8 h / 20 - 30 °C 3: hydrogenchloride / water / 4 h / 20 - 50 °C View Scheme

2I-O-(p-toluenesulfonyl)-β-cyclodextrin (84216-71-7) + L-anserine (584-85-0) → (2AS,3AR)-3A-[(3-{[(1S)-1-carboxy-2-(1-methyl-1H-imidazol-5-yl)ethyl]amino}-3-oxopropyl)amino]-3A-deoxy-β-cyclodextrin

Conditions	Yield
Stage #1: 2I-O-(p-toluenesulfonyl)-β-cyclodextrin With sodium hydrogencarbonate In water Stage #2: L-anserine In water at 60℃; for 40h; Further stages.;	37%

L-anserine (584-85-0) + soda lime → 1,2-dimethylimidazole (10447-93-5)

L-anserine (584-85-0) + barytes water → 3-methylhistidine (368-16-1, 7212-31-9, 13146-97-9) + 3-amino propanoic acid (107-95-9)

Conditions	Yield
at 140℃;

L-anserine (584-85-0) + trichlorophosphate (10025-87-3, 12599-09-6, 63736-95-8) → 3-methyl-Nα--L-histidine + 5-<(S)-2-carboxy-2-<(N-phosphono-β-alanyl)-amino>-ethyl>-3-methyl-1-phosphono-imidazolium + Nα-β-alanyl-3-methyl-1-phosphono-L-histidine

Conditions	Yield
ueber die Phosphorylierung;

L-anserine (584-85-0) + NaHPO3(NH2) → 3-methyl-Nα--L-histidine + 5-<(S)-2-carboxy-2-<(N-phosphono-β-alanyl)-amino>-ethyl>-3-methyl-1-phosphono-imidazolium + Nα-β-alanyl-3-methyl-1-phosphono-L-histidine

Conditions	Yield
ueber die Phosphorylierung;

methanol (67-56-1) + L-anserine (584-85-0) → β-alanyl-3-methyl-L-histidine methyl ester (1018683-10-7)

Conditions	Yield
With hydrogenchloride at 0℃;

L-anserine (584-85-0) → C10H16N4O4

Conditions	Yield
With oxygen; copper(II) sulfate; ascorbic acid In aq. phosphate buffer at 20℃; for 0.5h; pH=7.2;

Upstream product

• 368-16-1 3-methyl-L-histidine 
• 107-95-9 3-amino propanoic acid 
• 368-16-1 3-methylhistidine 
• 952739-81-0 N(α)-(3-((tert-butoxycarbonyl)amino)propylcarbonyl)-N(τ)-methyl-L-histidine methyl ester 
• 1018683-10-7 β-alanyl-3-methyl-L-histidine methyl ester 

Downstream Products

• 368-16-1 3-methylhistidine 
• 107-95-9 3-amino propanoic acid 

Relevant articles and documents

An expedient, scalable synthesis of the natural product L-anserine

To date, the synthesis of L-anserine has relied on the use of naturally occurring 1-methyl-L-histidine as a precursor, however its high cost prevents its use in the large-scale synthesis of L-anserine. With this in mind, we report herein a concise and efficient synthetic strategy, employing the 160-fold less expensive, L-histidine methyl ester dihydrochloride as a starting material, to afford the title compound in an overall yield of 88%, over four reaction steps. Georg Thieme Verlag Stuttgart.

Preparation methods of two kinds of anserine and immediate of anserine

The invention provides preparation methods of two kinds of anserine and a preparation method of a synthetic anserine intermediate. The preparation methods are simple to operate, easy to implement, stable in process, easy to control, convenient for reaction post-treatment, good in product yield, high in purity and capable of being economically and conveniently used for industrial production.

Concise Synthesis of Anserine: Efficient Solvent Tuning in Asymmetric Hydrogenation Reaction

A concise synthesis of anserine and related compounds was accomplished by Et-DuPhos-Rh-catalyzed asymmetric hydrogenation of dehydrohistidine derivatives in 2,2,2-trifluoroethanol, which played a key role in improving the yield and selectivity.