13485-59-1

Basic information

• Product Name: L-Alanyl-L-proline
• Synonyms: (S)-1-((S)-2-Aminopropanoyl)pyrrolidine-2-carboxylic acid;L-Proline, L-alanyl-;ALA-PRO;L-ALA-PRO H2O;L-ALANYL-L-PROLINE;H-ALA-PRO-OH;alanylproline;1-L-alanyl-L-proline
• CAS NO: 13485-59-1
• Molecular Formula: C₈H₁₄N₂O₃
• Molecular Weight: 186.21
• EINECS: 236-795-8
• Product Categories: Biochemistry;Oligopeptides;Peptide Synthesis
• Mol File: 13485-59-1.mol
• Article Data: 18

Chemical Properties

• Melting Point: 170-178 °C
• Boiling Point: 403.8 °C at 760 mmHg
• Flash Point: 198 °C
• Appearance: /
• Density: 1.294 g/cm³
• Vapor Pressure: 1.2E-07mmHg at 25°C
• Refractive Index: -112 ° (C=2, H2O)
• Storage Temp.: −20°C
• Solubility: Methanol (Slightly), Water (Slightly)
• PKA: 3.19±0.20(Predicted)
• Water Solubility: within almost transparency
• BRN: 3546017
• CAS DataBase Reference: L-Alanyl-L-proline(CAS DataBase Reference)
• NIST Chemistry Reference: L-Alanyl-L-proline(13485-59-1)
• EPA Substance Registry System: L-Alanyl-L-proline(13485-59-1)

Safety Data

• WGK Germany: 3
• F: 10-21
• Hazardous Substances Data: 13485-59-1(Hazardous Substances Data)

Usage

Uses

L-Alanyl-L-proline is a dipeptide that contains a sterically constrained proline, a well-known turn inducer in proteins.

Definition

ChEBI: A dipeptide composed of L-alanine and L-proline joined by a peptide linkage.

Biochem/physiol Actions

Alanyl dipeptides such as ala-leu, ala-lys, ala-gly, ala-pro, ala-tyr and ala-phe may be used in physicochemical studies or to evaluate dipeptide separation technologies. Alanyl dipeptides may also be used for studying cell uptake mechanisms, dipeptide metabolism or cell growth supplementation benefits.

InChI:InChI=1/C8H14N2O3/c1-5(9)7(11)10-4-2-3-6(10)8(12)13/h5-6H,2-4,9H2,1H3,(H,12,13)

Synthetic route

N-benzyloxycarbonyl-L-alanyl-L-proline (21027-01-0) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
With acetic acid; 10% palladium on active carbon In methanol for 2h; Hydrogenation;	98%
With hydrogen; palladium on activated charcoal In sodium hydroxide

(S)-1-((S)-2-Phosphonoamino-propionyl)-pyrrolidine-2-carboxylic acid (76166-63-7) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
With sodium chloride at 37℃; Rate constant; pH=7.5;

L-proline (147-85-3) + L-alanine N-carboxyanhydride (2224-52-4) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
With potassium hydroxide; potassium carbonate In tetrahydrofuran; water at 5 - 10℃; for 0.25h;	92 % Chromat.

N-tert-butoxycarbonyl-L-alanyl-L-proline (33300-72-0) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
With methoxybenzene; trifluoroacetic acid
With hydrogenchloride In ethyl acetate
With trifluoroacetic acid In dichloromethane at 0℃; for 3h;
Multi-step reaction with 2 steps 1: N,O-bis-(trimethylsilyl)-acetamide / acetonitrile / 0.5 h / 20 °C 2: tetra(n-butyl)ammonium hydroxide; water / methanol; tert-butyl methyl ether / 12 h View Scheme

L-proline (147-85-3) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: BOP; DIPEA / CH2Cl2 2: HCl / ethyl acetate View Scheme
Multi-step reaction with 2 steps 2: TFA, anisole View Scheme

L-proline ethyl ester monohydrochloride (33305-75-8) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 83 percent / ethyl acetate; dimethylformamide / 2 h / -10 - 20 °C 2: 85 percent / NaOH; HCl / methanol; CH2Cl2 / 3 h 3: 98 percent / acetic acid / 10 percent Pd/C / methanol / 2 h View Scheme

N-carbobenzoxy-β-alanylproline ethyl ester → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 85 percent / NaOH; HCl / methanol; CH2Cl2 / 3 h 2: 98 percent / acetic acid / 10 percent Pd/C / methanol / 2 h View Scheme

(naphth-1-yl)methylamine (118-31-0) + 1-pyruvyl-L-proline (76391-12-3) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
With nitrogen; palladium In ethanol
With nitrogen; palladium In ethanol

1-pyruvyl-L-proline (76391-12-3) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
With hydrogenchloride; nitrogen; hydroxylamine hydrochloride; sodium acetate; palladium hydroxide-on-carbon In ethanol; water
With hydrogenchloride; nitrogen; hydroxylamine hydrochloride; sodium acetate; palladium hydroxide-on-carbon In ethanol; water

Fmoc-Ala-Pro-OH (186023-44-9) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
With piperidine In N,N-dimethyl-formamide for 0.5h;

methyl (2S)-pyrrolidine carboxylate (2577-48-2) → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0.25 h / 0 °C 1.2: 24 h 2.1: lithium hydroxide / tetrahydrofuran; water / 5 h / 0 °C 3.1: trifluoroacetic acid / dichloromethane / 3 h / 0 °C View Scheme

C16H30N2O5Si → L-alanyl-L-proline (13485-59-1)

Conditions	Yield
With tetra(n-butyl)ammonium hydroxide; water In methanol; tert-butyl methyl ether for 12h;

L-alanyl-L-proline (13485-59-1) + p-toluenesulfonyl chloride (98-59-9) → N-p-toluenesulfonyl-L-alanyl-L-proline

Conditions	Yield
With sodium hydroxide In 1,4-dioxane; aqueous sodium hydroxide (10 ml)-dioxane; water	95.8%

L-alanyl-L-proline (13485-59-1) + 4-phenyl-butyric acid 4-guanidino-phenyl ester → 4-phenylbutanoyl-L-alanyl-L-proline

Conditions	Yield
With HEPES buffer; sodium chloride; calcium chloride; clostripain (EC 3.4.22.8) In water; N,N-dimethyl-formamide at 25℃; pH=8.0; Acylation;	93%

L-alanyl-L-proline (13485-59-1) + 3-benzoylamino-propionic acid 4-guanidino-phenyl ester → Bz-β-Ala-Ala-Pro-OH

Conditions	Yield
With HEPES buffer; sodium chloride; calcium chloride; clostripain (EC 3.4.22.8) In water; N,N-dimethyl-formamide at 25℃; pH=8.0; Acylation;	91%

ethanol (64-17-5) + L-alanyl-L-proline (13485-59-1) → L-alanyl-L-proline ethyl ester hydrochloride (88098-06-0)

Conditions	Yield
With hydrogenchloride for 2h; Heating;	90%

C27H33N9O9 + L-alanyl-L-proline (13485-59-1) → C29H42N10O9

Conditions	Yield
With benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 35℃; for 8h;	81.39%

L-alanyl-L-proline (13485-59-1) + N-(pyrazinecarbonyl)glycine azide (117904-03-7) → N--L-alanyl>-L-proline

Conditions	Yield
With sodium methylate In N,N-dimethyl-formamide for 70h; Ambient temperature;	72%

L-alanyl-L-proline (13485-59-1) + Ethyl 4-(β-indolyl)-2-ketobutyrate (79155-18-3) → N-[1-ethoxycarbonyl-3-(3-indolyl)propyl]-L-alanyl-L-proline (79155-17-2)

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol at 25℃; under 2068.6 Torr;	70%

2-oxo-4-phenylbutanoic acid ethyl ester (64920-29-2) + L-alanyl-L-proline (13485-59-1) → enalapril (75847-73-3)

Conditions	Yield
With hydrogen In ethanol at 45℃; under 735.074 - 772.577 Torr; Catalytic behavior; Kinetics; Solvent; Reagent/catalyst;	70%

L-alanyl-L-proline (13485-59-1) + (E)-ethyl-2-oxo-4-phenylbut-3-enoate (17451-20-6, 55674-14-1, 55629-96-4) → enalapril (75847-73-3)

Conditions	Yield
With 4 A molecular sieve; hydrogen; triethylamine; palladium In ethanol at 20℃; for 44h;	65%

zinc(II) nitrate hexahydrate + L-alanyl-L-proline (13485-59-1) → C16H26N4O6Zn

Conditions	Yield
In methanol for 1h;	64%

copper(II) nitrate trihydrate + L-alanyl-L-proline (13485-59-1) → C16H26CuN4O6

Conditions	Yield
In methanol for 1h;	62.35%

L-alanyl-L-proline (13485-59-1) + 4-[1-(3-Nitro-pyridin-2-ylamino)-meth-(Z)-ylidene]-2-phenyl-4H-oxazol-5-one → (S)-1-{(S)-2-[(Z)-2-Benzoylamino-3-(3-nitro-pyridin-2-ylamino)-acryloylamino]-propionyl}-pyrrolidine-2-carboxylic acid

Conditions	Yield
With sodium carbonate In water; acetonitrile for 2h; Heating;	40%

L-alanyl-L-proline (13485-59-1) + 2-phenyl-4-(5-ethoxycarbonyl-2-methylthio-4-pyrimidinylamino)methylene-5(4H)-oxazolone (124211-85-4) → 4-{(Z)-2-Benzoylamino-2-[(S)-2-((S)-2-carboxy-pyrrolidin-1-yl)-1-methyl-2-oxo-ethylcarbamoyl]-vinylamino}-2-methylsulfanyl-pyrimidine-5-carboxylic acid ethyl ester

Conditions	Yield
With sodium carbonate In water; acetonitrile for 2h; Heating;	39%

L-alanyl-L-proline (13485-59-1) + 2-phenyl-4-(4-chloro-6-methyl-2-pyrimidinylamino)methylene-5(4H)-oxazolone (124594-30-5) → (S)-1-{(S)-2-[(Z)-2-Benzoylamino-3-(4-chloro-6-methyl-pyrimidin-2-ylamino)-acryloylamino]-propionyl}-pyrrolidine-2-carboxylic acid

Conditions	Yield
With sodium carbonate In water; acetonitrile for 2h; Heating;	36%

trimethylsilyl cyanide (7677-24-9) + L-alanyl-L-proline (13485-59-1) + tert-butoxycarbonyl-D-prolinal (73365-02-3) → C19H30N4O5

Conditions	Yield
With ammonium chloride In methanol at 25℃; for 36h;	36%

L-alanyl-L-proline (13485-59-1) → pyrrolidino[1,2-a]-2,6-diazacycloheptane-1,5-dione

Conditions	Yield
In acetic anhydride for 2.5h; Cyclization; Heating;	33%

3-phenyl-propionaldehyde (104-53-0) + L-alanyl-L-proline (13485-59-1) + potassium cyanide (151-50-8) → (S)-1-[(S)-2-(1-Cyano-3-phenyl-propylamino)-propionyl]-pyrrolidine-2-carboxylic acid (138247-41-3)

Conditions	Yield
With acetic acid In methanol

4-phthalimidobutanal (3598-60-5) + L-alanyl-L-proline (13485-59-1) + potassium cyanide (151-50-8) → (S)-1-{(S)-2-[1-Cyano-4-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-butylamino]-propionyl}-pyrrolidine-2-carboxylic acid

Conditions	Yield
With acetic acid In methanol for 48h;

3,3-dimethyl acrylaldehyde (107-86-8) + L-alanyl-L-proline (13485-59-1) + potassium cyanide (151-50-8) → (S)-1-[(S)-2-(1-Cyano-3-methyl-but-2-enylamino)-propionyl]-pyrrolidine-2-carboxylic acid

Conditions	Yield
With acetic acid In methanol for 48h;

2-(benzoylamino)acetaldehyde (6542-76-3) + L-alanyl-L-proline (13485-59-1) + potassium cyanide (151-50-8) → (S)-1-[(S)-2-(2-Benzoylamino-1-cyano-ethylamino)-propionyl]-pyrrolidine-2-carboxylic acid

Conditions	Yield
With acetic acid In methanol for 48h;
In methanol for 72h;

N-tert.butyloxycarbonyl-alanine pentafluorophenyl ester (50903-48-5) + L-alanyl-L-proline (13485-59-1) → N-tert-butyloxycarbonyl-alanyl-alanyl-proline (63769-98-2)

Conditions	Yield
In 1,4-dioxane for 24h;

2-oxo-4-phenylbutanoic acid ethyl ester (64920-29-2) + L-alanyl-L-proline (13485-59-1) → enalapril (75847-73-3) + enalapril (76420-74-1)

Conditions	Yield
nickel Product distribution; var. catalysts and reducing agents, diastereomeric ratio;
With 3 A molecular sieve; hydrogen; nickel In ethanol at 23 - 28℃; under 2068.6 Torr; for 18h; Title compound not separated from byproducts;
With potassium fluoride; 3 A molecular sieve; hydrogen; acetic acid; nickel In ethanol at 22℃; under 760 Torr; for 18h; Yield given; Yields of byproduct given;

2-oxo-4-phenylbutanoic acid ethyl ester (64920-29-2) + L-alanyl-L-proline (13485-59-1) → (S)-1-{(S)-2-[1-Ethoxycarbonyl-3-phenyl-prop-(E)-ylideneamino]-propionyl}-pyrrolidine-2-carboxylic acid (90414-32-7)

Conditions	Yield
With 4 A molecular sieve In ethanol

L-alanyl-L-proline (13485-59-1) + Boc-L-Pro-H (69610-41-9) + potassium cyanide (151-50-8) → C19H30N4O5

Conditions	Yield
In methanol for 96h;

L-alanyl-L-proline (13485-59-1) + Boc-L-phenylalaninal (72155-45-4) + potassium cyanide (151-50-8) → (S)-1-[(S)-2-((S)-2-tert-Butoxycarbonylamino-1-cyano-3-phenyl-propylamino)-propionyl]-pyrrolidine-2-carboxylic acid (94670-41-4, 94730-84-4)

Conditions	Yield
With acetic acid In methanol for 72h;

L-alanyl-L-proline (13485-59-1) + potassium cyanide (151-50-8) + 3-[(tert-butoxycarbonyl)amino]-4-phenylbutanaldehyde (130944-47-7) → (S)-1-[(S)-2-((S)-3-tert-Butoxycarbonylamino-1-cyano-4-phenyl-butylamino)-propionyl]-pyrrolidine-2-carboxylic acid

Conditions	Yield
With acetic acid In methanol for 48h;

L-alanyl-L-proline (13485-59-1) + potassium cyanide (151-50-8) + (3S)-3-benzamido-4-phenylbutanal (94670-46-9) → (S)-1-[(S)-2-((S)-3-Benzoylamino-1-cyano-4-phenyl-butylamino)-propionyl]-pyrrolidine-2-carboxylic acid

Conditions	Yield
With acetic acid In methanol for 72h;

Upstream product

• 147-85-3 L-proline 
• 115116-62-6 1-((Ξ)-2-bromo-propionyl)-L-proline 
• 118-31-0 (naphth-1-yl)methylamine 
• 76391-12-3 1-pyruvyl-L-proline 
• 33305-75-8 L-proline ethyl ester monohydrochloride 
• 33300-72-0 N-tert-butoxycarbonyl-L-alanyl-L-proline 
• 2224-52-4 L-alanine N-carboxyanhydride 
• 76166-63-7 (S)-1-((S)-2-Phosphonoamino-propionyl)-pyrrolidine-2-carboxylic acid 
• 21027-01-0 N-benzyloxycarbonyl-L-alanyl-L-proline 
• 23458-22-2 Cbz-Ala-Pro-OBzl 
• 35661-39-3 N-[(9H-fluoren-9-ylmethoxy)carbonyl]-L-alanine 
• 2133-40-6 L-proline methyl ester monohydrochloride 
• 2577-48-2 methyl (2S)-pyrrolidine carboxylate 
• 186023-44-9 Fmoc-Ala-Pro-OH 

Downstream Products

• 75847-73-3 enalapril 
• 76420-74-1 enalapril 
• 90414-32-7 (S)-1-{(S)-2-[1-Ethoxycarbonyl-3-phenyl-prop-(E)-ylideneamino]-propionyl}-pyrrolidine-2-carboxylic acid 
• 94670-42-5 N-<1-carboxamido-2-<(tert-butoxycarbonyl)amino>-3-phenylpropyl>-Ala-Pro-OCH3 
• 94670-65-2 ethanolN--Ala-Pro-OEt 
• 94706-14-6 N-methyl>-Ala-Pro 
• 94670-61-8 N-methyl>-Ala-Pro-OCH3 
• 94670-67-4 N--Ala-Pro*HCl 
• 94670-63-0 N-α-pyroglutamyl-N^ε-carbobenzoxylysyl-2-pyrrolidinyl)methyl>-Ala-Pro-OCH3 
• 94670-43-6 (S)-1-[(S)-2-((S)-2-Amino-1-methoxycarbonyl-3-phenyl-propylamino)-propionyl]-pyrrolidine-2-carboxylic acid methyl ester 
• 94670-43-6 (S)-1-[(S)-2-((1S,2S)-2-Amino-1-methoxycarbonyl-3-phenyl-propylamino)-propionyl]-pyrrolidine-2-carboxylic acid methyl ester 
• 94730-83-3 N-(2-benzamido-1-carboxy-3-phenylpropyl)-Ala-Pro 
• 94730-82-2 N-(2-benzamido-1-carboxy-3-phenylpropyl)-Ala-Pro 
• 94730-86-6 N-(2-benzamido-1-carbomethoxy-3-phenylpropyl)-Ala-Pro-OCH₃ 

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