24697-74-3

Basic information

• Product Name: Leonurine hydrochloride
• Synonyms: 4-Guanidino-1-butanol syringate;Leonurine 4-Guanidino-1-butanol syringate;SCM-198;4-(diaminomethylideneamino)butyl 4-hydroxy-3,5-dimethoxy-benzoate hydrochloride;leonurine hydrochloride;Leonurine;LEONURINE HCL;4-Hydroxy-3,5-dimethoxybenzoic acid 4-guanidinobutyl ester
• CAS NO: 24697-74-3
• Molecular Formula: C₁₄H₂₁N₃O₅
• Molecular Weight: 347.79458
• EINECS: 1592732-453-0
• Product Categories: phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;chemical reagent;pharmaceutical intermediate
• Mol File: 24697-74-3.mol
• Article Data: 6

Chemical Properties

• Melting Point: 238 °C
• Boiling Point: 531.6 °C at 760 mmHg
• Flash Point: 275.3 °C
• Appearance: white to beige/
• Density: 1.29 g/cm³
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble2mg/mL, clear (warmed)
• PKA: 8.26±0.25(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 1 month.
• CAS DataBase Reference: Leonurine hydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Leonurine hydrochloride(24697-74-3)
• EPA Substance Registry System: Leonurine hydrochloride(24697-74-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-24/25
• WGK Germany: 3
• Hazardous Substances Data: 24697-74-3(Hazardous Substances Data)

Usage

Description

Leonurine hydrochloride, a pseudoalkaloid derived from the Leonotis leonurus plant, is an amorphous alkaloid obtained from the leaves of Leonurus sibericus L. It is characterized as a crystalline hydrochloride hydrate with a melting point of 191-194°C. Upon hydrolysis, it yields syringic acid and Q-hydroxybutylguanidine. The total synthesis of the alkaloid has been achieved, confirming its structure. Leonurine hydrochloride possesses antioxidant, anti-inflammatory, and cardioprotective properties, making it a valuable compound for the treatment of various conditions.

Uses

Used in Pharmaceutical Applications:
Leonurine hydrochloride is used as a therapeutic agent for the treatment of various cardiovascular diseases, including stroke, cerebral thrombosis, and other related conditions. Its antioxidant, anti-inflammatory, and cardioprotective properties contribute to its effectiveness in managing these health issues.
Used in Antioxidant Applications:
Leonurine hydrochloride is used as an antioxidant agent to protect cells from oxidative stress and damage, which can lead to various diseases and conditions. Its antioxidant properties help in maintaining overall health and well-being.
Used in Anti-Inflammatory Applications:
Leonurine hydrochloride is used as an anti-inflammatory agent to reduce inflammation and alleviate pain associated with various conditions, such as arthritis and other inflammatory disorders.
Used in Cardioprotective Applications:
Leonurine hydrochloride is used as a cardioprotective agent to support heart health and prevent damage to the cardiovascular system. Its cardioprotective properties help in maintaining a healthy heart and reducing the risk of heart-related diseases.

References

Kubota, Nakajima., Nippon Yakubusugaku Zasshi., 163 (1930) Goto et al., Tetrahedron Lett., 545 (1962) Total synthesis: Kishi et al., Tetrahedron Lett., 637 (1968)

InChI:InChI=1/C14H21N3O5.ClH.H2O/c1-20-10-7-9(8-11(21-2)12(10)18)13(19)22-6-4-3-5-17-14(15)16;;/h7-8,18H,3-6H2,1-2H3,(H4,15,16,17);1H;1H2

Synthetic route

4-(2,3-bis(tert-butoxycarbonyl)guanidino)butyl 4-hydroxy-3,5-dimethoxybenzoate → Leonurine (24697-74-3)

Conditions	Yield
With zinc dibromide In dichloromethane at 20℃;	93%

S-methylisothiourea hemisulphate + Leonuramin (18780-70-6) → Leonurine (24697-74-3)

Conditions	Yield
In water; N,N-dimethyl-formamide at 120℃; for 6h;	65%

Leonuramin (18780-70-6) + S-Methylisothiourea sulfate (867-44-7) → Leonurine (24697-74-3)

Conditions	Yield
In water; N,N-dimethyl-formamide at 120℃; for 6h;	65%

Leonuramin (18780-70-6) + N,N'-bis-Boc-S-methyl-isothiourea (322474-21-5) → Leonurine (24697-74-3) + 3,5-dimethoxy-4-hydroxybenzoic acid-4-(N,N'-diBoc-guanidino)butyl ester (1260119-24-1)

Conditions	Yield
In N,N-dimethyl-formamide at 60℃;	A 30% B 5%

4-ethoxycarbonyloxy-3,5-dimethoxy-benzoyl chloride (18780-68-2) → Leonurine (24697-74-3)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: triethylamine; dmap / dichloromethane / 6 h / 0 - 20 °C 2.1: ammonium hydroxide / methanol / 4 h / 20 °C 2.2: Raney nickel / 10 h / 20 °C 3.1: water; N,N-dimethyl-formamide / 6 h / 120 °C View Scheme
Multi-step reaction with 4 steps 1: triethylamine; dmap / dichloromethane / 0 - 20 °C 2: ammonium hydroxide / methanol / 20 °C 3: hydrogen / methanol / 10 h / 25 °C / 760.05 Torr 4: N,N-dimethyl-formamide; water / 6 h / 120 °C View Scheme

4-[(ethoxycarbonyl)oxy]-3,5-dimethoxybenzoic acid (18780-67-1) → Leonurine (24697-74-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: thionyl chloride / 1 h / Reflux 2.1: triethylamine; dmap / dichloromethane / 6 h / 0 - 20 °C 3.1: ammonium hydroxide / methanol / 4 h / 20 °C 3.2: Raney nickel / 10 h / 20 °C 4.1: water; N,N-dimethyl-formamide / 6 h / 120 °C View Scheme
Multi-step reaction with 5 steps 1: thionyl chloride / Reflux 2: triethylamine; dmap / dichloromethane / 0 - 20 °C 3: ammonium hydroxide / methanol / 20 °C 4: hydrogen / methanol / 10 h / 25 °C / 760.05 Torr 5: N,N-dimethyl-formamide; water / 6 h / 120 °C View Scheme

3,5-dimethoxy-4-hydroxybenzoic acid (530-57-4) → Leonurine (24697-74-3)

Conditions	Yield
Multi-step reaction with 6 steps 1: sodium hydroxide / 6 h / Cooling 2: thionyl chloride / Reflux 3: triethylamine; dmap / dichloromethane / 0 - 20 °C 4: ammonium hydroxide / methanol / 20 °C 5: hydrogen / methanol / 10 h / 25 °C / 760.05 Torr 6: N,N-dimethyl-formamide; water / 6 h / 120 °C View Scheme
Multi-step reaction with 5 steps 1.1: dmap / dichloromethane / 20 h 2.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 1 h / 20 °C 2.2: 6 h / 20 °C 3.1: trifluoromethylsulfonic anhydride; triethylamine / dichloromethane / 6 h 4.1: acetic acid; zinc / 2 h 5.1: N,N-dimethyl-formamide / 5 h / 140 °C View Scheme
Multi-step reaction with 4 steps 1: triethylamine / dichloromethane / 5 h / 20 °C 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 20 °C 3: sodium hydroxide / methanol / 20 °C 4: zinc dibromide / dichloromethane / 20 °C View Scheme

C17H23NO8 → Leonurine (24697-74-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: ammonium hydroxide / methanol / 20 °C 2: hydrogen / methanol / 10 h / 25 °C / 760.05 Torr 3: N,N-dimethyl-formamide; water / 6 h / 120 °C View Scheme

C15H19NO7 → Leonurine (24697-74-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: trifluoromethylsulfonic anhydride; triethylamine / dichloromethane / 6 h 2: acetic acid; zinc / 2 h 3: N,N-dimethyl-formamide / 5 h / 140 °C View Scheme

C15H21NO6 + carbamimidothioic acid methyl ester (2986-19-8) → Leonurine (24697-74-3)

Conditions	Yield
In N,N-dimethyl-formamide at 140℃; for 5h;	17 g

O-acetylsyringic acid (6318-20-3) → Leonurine (24697-74-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / dichloromethane / 1 h / 20 °C 1.2: 6 h / 20 °C 2.1: trifluoromethylsulfonic anhydride; triethylamine / dichloromethane / 6 h 3.1: acetic acid; zinc / 2 h 4.1: N,N-dimethyl-formamide / 5 h / 140 °C View Scheme
Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 20 °C 2: sodium hydroxide / methanol / 20 °C 3: zinc dibromide / dichloromethane / 20 °C View Scheme

4-(2,3-bis(tert-butoxycarbonyl)guanidino)butyl-4-acetoxy-3,5-dimethoxybenzoate → Leonurine (24697-74-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium hydroxide / methanol / 20 °C 2: zinc dibromide / dichloromethane / 20 °C View Scheme

C15H29N3O5 → Leonurine (24697-74-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; dmap / dichloromethane / 20 °C 2: sodium hydroxide / methanol / 20 °C 3: zinc dibromide / dichloromethane / 20 °C View Scheme

Leonurine (24697-74-3) + UDP-glucuronic acid (2616-64-0) → leonurine-O-glucuronide + C13H19N3O5

Conditions	Yield
With recombinant human UDP-glucuronosyltransferase UGT1A1; NADPH; magnesium chloride In aq. phosphate buffer at 37℃; for 1h; pH=7.4; Catalytic behavior; Kinetics; Reagent/catalyst; Concentration; Enzymatic reaction;

Upstream product

• 2986-19-8 carbamimidothioic acid methyl ester 
• 6318-20-3 O-acetylsyringic acid 
• 18780-70-6 Leonuramin 
• 867-44-7 S-Methylisothiourea sulfate 
• 530-57-4 3,5-dimethoxy-4-hydroxybenzoic acid 
• 18780-67-1 4-[(ethoxycarbonyl)oxy]-3,5-dimethoxybenzoic acid 
• 147895-43-0 S-methylisothiourea hemisulphate 
• 18780-68-2 4-ethoxycarbonyloxy-3,5-dimethoxy-benzoyl chloride 
• 322474-21-5 N,N'-bis-Boc-S-methyl-isothiourea 

Downstream Products

• 1470302-79-4 leonurine-O-glucuronide 

Relevant articles and documents

Leonurine, an improved synthesis

The uterotonic principle of Leonurus artemisia, a plant leaf, is leonurine. This paper reports the development of a simple, high-yield synthetic procedure of reproducing leonurine that is adaptable to large-scale preparation. The synthetic process includes condensation of syringic acid and 4-guanidino-1-butanol hydrochloride in the presence of dicyclohexylcarbodiimide, using 1:1 hexamethylphosphoric triamide-ethyl ether as solvent. Synthetic leonourine showed uterotonic activity in vitro and in vivo, just like its naturally occurring counterpart.

Synthetic method for leonurine

The invention relates to the technical field of organic chemistry, in particular to a synthetic method for leonurine. Gamma-butyrolactone is used as a starting material to be subjected to ammonolysis to obtain gamma-hydroxybutyric acid amide; the gamma-hydroxybutyric acid amide and acetyl syringic acid are subjected to a condensation reaction; a dehydration reaction and a reduction reaction are carried out to obtain leonurus amine; and the leonurus amine and S-methyl isothiourea sulfate are subjected to a reaction to obtain the leonurine. The target product leonurine is synthetized from the cheap industrial raw materials of the gamma-butyrolactone and the syringic acid used as the starting materials through reactions of ammonolysis, esterification, dehydration, reduction and the like. The reaction conditions are mild and easy to control; the yield is up to 65%; the product purity is 98% or above; and the synthetic method for leonutine provides the production with an excellent synthetic route and is suitable for large-scale production.

Herba Leonuri (motherwort) a method of synthesis of alkali (by machine translation)

The invention discloses a method of synthesis for alkali Herba Leonuri (motherwort), characterized in that the raw material is 2,3-dihydrofuran [...] of the synthesis reaction, a product of the obtained 4-hydroxy butyl-O-oxime and alkoxyl carbonylation Syzygium aromaticum (clove) acid through esterification reaction, is obtained by reacting [...]leonurus siribicus amine, then the leonurus siribicus amine and methyl isothiourea reaction, to obtain Herba Leonuri (motherwort) alkali. The reaction process of the present invention good atom economy, to avoid excess use of the reagent, the pollution to the environment is reduced, high yield, the operation is easy. (by machine translation)