Andrographolide

Base Information

• Chemical Name: Andrographolide
• CAS No.: 5508-58-7
• Deprecated CAS: 101060-34-8,5953-53-7
• Molecular Formula: C20H30O5
• Molecular Weight: 350.45
• Hs Code.: 29322980
• European Community (EC) Number: 226-852-5
• UNII: 410105JHGR
• DSSTox Substance ID: DTXSID3045980
• Nikkaji Number: J3.154.642G
• Wikipedia: Andrographolide
• Wikidata: Q4759444
• NCI Thesaurus Code: C61637
• Metabolomics Workbench ID: 63852
• ChEMBL ID: CHEMBL186141
• Mol file: 5508-58-7.mol

Synonyms:17-hydro-9-dehydro-andrographolide;andrographolide;isoandrographolide

Chemical Property of Andrographolide

Chemical Property:

• Appearance/Colour: powder
• Vapor Pressure: 9.64E-15mmHg at 25°C
• Melting Point: 229-232 °C(lit.)
• Refractive Index: 1.567
• Boiling Point: 557.3 °C at 760 mmHg
• PKA: 12.36±0.20(Predicted)
• Flash Point: 195.5 °C
• PSA: 86.99000
• Density: 1.21 g/cm³
• LogP: 1.96260
• Storage Temp.: +2C to +8C
• Solubility.: Soluble in DMSO (up to 25 mg/ml) or in Ethanol (up to 8 mg/ml).
• XLogP3: 2.2
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 3
• Exact Mass: 350.20932405
• Heavy Atom Count: 25
• Complexity: 597

Purity/Quality:

high content 98%,lower content 10%, ^*data from raw suppliers

Andrographolide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38
• Safety Statements: 22-24/25-36-26

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC12CCC(C(C1CCC(=C)C2CC=C3C(COC3=O)O)(C)CO)O
• Isomeric SMILES: C[C@@]12CC[C@H]([C@@]([C@H]1CCC(=C)[C@H]2C/C=C/3\[C@@H](COC3=O)O)(C)CO)O
• Recent ClinicalTrials: Phase II Study of HMPL-004 in Patients With Ulcerative Colitis
• Recent EU Clinical Trials: A Phase III Double Blind, Multi-Center Placebo Controlled Maintenance Trial of HMPL-004 in Subjects with Mild to Moderate Ulcerative Colitis with Clinical Remission or Response from Induction Therapy. (NATRUL-4)
• Description: Andrographolide is the bitter principle, a colorless and neutral crystalline substance. It is the major labdane diterpenoid isolated from Andrographis paniculate. It exhibits antiviral, anti-inflammatory, and anticancer activities. The underlying mechanism is the inhibition of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling (specifically p38 MAPK/ERK1/2) pathway and downstream transcription factors such as nuclear factor kappa B (NF-κB) and nuclear factor of activated T cells (NFAT). Andrographolide is also confirmed with chemopreventive effects against and the inhibitory effects on cancer cell growth in breast, colon, epidermoid, gastric, liver, leukemia, myeloma, peripheral blood lymphocytes, and prostate cancers. Andrographolide has been used for liver complaints and fever, and as an anti-inflammatory and immunostimulant. Andrographolide exerts anti-growth and pro-apoptotic effects on human rheumatoid arthritis fibroblast- like synoviocytes, the main cellular constituent of pannus, that combined with a massive infiltration of lymphocytes and macrophages, invades and destroys the local articular structure. Thereby, andrographolide is proposed to be used in Rheumatoid Arthritis and other autoimmune diseases. Andrographolide is a diterpene lactone compound extracted from Andrographis. paniculata (Burm. F) Nees. Andrographis paniculata is also known as lanhelian, yijianxi, zhanshecao, kucao, kudancao, etc. Since this product originates in India, it is also known as Indian grass. This product is dry ground part of Jupiteraceae plant Andrographis paniculata (conus) may originate in South Asia. It is commonly cultivated in China such as in Fujian, Guangdong, Hainan, Guangxi, and Yunnan and also in Australia and was also introduced in Jiangsu and Shaanxi.Andrographis paniculata is commonly used in traditional Chinese medicine. Its ability of relieving “snake venom, and internal injuries cough” was recorded in “Lingnan herbal medicine records.” “Quanzhou Materia Medica” described it as “heat-clearing and detoxifying, anti-inflammatory, detumescence and inhibition throat inflammation, dysentery and high fever.”The above ground part of Andrographis paniculata contains andrographolide, neo-andrographolide, 14-deoxygenated andrographolide, etc., and the root contains mainly flavonoids.
• Uses: Andrographolide is a labdane diterpenoid. Andrographolide is the main bioactive component isolated from the medicinal plant Andrographis paniculata. It has a broad range of therapeutic applications including anti-inflammatory and anti-platelet aggregation activities and potential antineoplastic properties. Andrographolide showed significant antihepatotoxic action in P. berghei K173- induced hepatic damage in M. natalensis. Andrographolide inhibits tumor necrosis factor-α (TNF-α)-induced intercellular adhesion mol.-1 (ICAM-1) expression and adhesion of HL-60 cells onto human umbilical vein endothelial cells (HUVEC), which are associated with inflammatory diseases. These findings suggest that Andrographolide may have potential as a cardiovascular-protective agent.
• Clinical Use: This product is commonly used clinically for dysentery, leptospirosis, meningitis, pneumonia, upper respiratory tract infection, and enhancing adrenal cortical function. In view of the requirement for clinical viral infection emergency, it is important to introduce the hydrophilic group in different lactone structure, enhance its water solubility, and improve efficacy. There are a variety kinds of andrographolide injection, including potassium dehydroandrograpolide succinate needle, potassium sodium dehydroandrographolide succinate needle. Lianbizhi is the representative of this class of drugs in current clinical application. Oral administration of andrographolide may induce bitter vomiting. Oral administration of this product and other preparations in large doses can cause epigastric discomfort and loss of appetite. It had been reported of drug eruption, upper abdominal pain, and anaphylactic shock caused by intramuscular injection. Severe symptom response emerged such as chest tightness, shortness of breath, pallor, lip bruising, cold sweats, weak pulse, decreased blood pressure, etc. Light reactions include abdominal pain, vomiting, asthma, urticaria, pimples, dizziness, head swelling, sneezing, chest pain, etc. The reaction is real time and also 5–20?min after injection and gradually improves 5–45?min after rescue and individual recovered by 24?h. There are also reports of acute amniotic fluid blockage caused by weaning lotion exchange. In addition, taking into account the adverse effects of andrographolide on reproduction, it is recommended to be used cautiously by fertility couples and pregnant women.

Technology Process of Andrographolide

There total 17 articles about Andrographolide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 92.0%

(S,E)-3-(2-((1R,4aS,5R,6R,8aS)-5,8a-dimethyl-2-methylene-6-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)decahydronaphthalen-1-yl)ethylidene)-4-hydroxydihydrofuran-2(3H)-one → andrographolide (142037-79-4,5508-58-7)

Guidance literature:

With pyridine; pyridine hydrogenfluoride; In tetrahydrofuran; at 0 - 20 ℃; for 34h; Inert atmosphere;

DOI:10.1002/anie.202011363

Reference yield:

((4aS,5R,6R,8aR)-5,8a-dimethyl-6-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)-3,4,4a,5,6,7,8,8a-octahydronaphthalene-1,2-diyl)dimethanol → andrographolide (142037-79-4,5508-58-7)

Guidance literature:

Multi-step reaction with 5 steps

1.1: di-isopropyl azodicarboxylate; triphenylphosphine; 2-nitrobenzenesulfonyl hydrazide / tetrahydrofuran / 7.5 h / -30 - 25 °C / Inert atmosphere

2.1: triphenylphosphine; 1H-imidazole; iodine / tetrahydrofuran / 24 h / 0 - 20 °C / Inert atmosphere

3.1: tert.-butyl lithium / diethyl ether; pentane / 1 h / -78 °C / Inert atmosphere

3.2: 0.08 h / -78 - 0 °C / Inert atmosphere

4.1: triethylamine; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; sodium carbonate; tetra-(n-butyl)ammonium iodide / 1,4-dioxane / 15 h / 80 °C / Inert atmosphere; Schlenk technique

5.1: pyridine hydrogenfluoride; pyridine / tetrahydrofuran / 34 h / 0 - 20 °C / Inert atmosphere

With pyridine; 1H-imidazole; di-isopropyl azodicarboxylate; 2-nitrobenzenesulfonyl hydrazide; iodine; tert.-butyl lithium; palladium diacetate; tetra-(n-butyl)ammonium iodide; sodium carbonate; pyridine hydrogenfluoride; triethylamine; triphenylphosphine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In tetrahydrofuran; 1,4-dioxane; diethyl ether; pentane;

DOI:10.1002/anie.202011363

Reference yield:

((1R,4aS,5R,6R,8aR)-5,8a-dimethyl-2-methylene-6-((triisopropylsilyl)oxy)-5-(((triisopropylsilyl)oxy)methyl)decahydronaphthalen-1-yl)methanol → andrographolide (142037-79-4,5508-58-7)

Guidance literature:

Multi-step reaction with 4 steps

1.1: triphenylphosphine; 1H-imidazole; iodine / tetrahydrofuran / 24 h / 0 - 20 °C / Inert atmosphere

2.1: tert.-butyl lithium / diethyl ether; pentane / 1 h / -78 °C / Inert atmosphere

2.2: 0.08 h / -78 - 0 °C / Inert atmosphere

3.1: triethylamine; palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; sodium carbonate; tetra-(n-butyl)ammonium iodide / 1,4-dioxane / 15 h / 80 °C / Inert atmosphere; Schlenk technique

4.1: pyridine hydrogenfluoride; pyridine / tetrahydrofuran / 34 h / 0 - 20 °C / Inert atmosphere

With pyridine; 1H-imidazole; iodine; tert.-butyl lithium; palladium diacetate; tetra-(n-butyl)ammonium iodide; sodium carbonate; pyridine hydrogenfluoride; triethylamine; triphenylphosphine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; In tetrahydrofuran; 1,4-dioxane; diethyl ether; pentane;

DOI:10.1002/anie.202011363

upstream raw materials:

geraniol

Downstream raw materials:

14-deoxy-11,12-didehydroandrographolide

14-deoxy-12-methoxy-andrographolide

19-Tr-andrographolide

Refernces