(+/-)-Huperzine A

Base Information

• Chemical Name: (+/-)-Huperzine A
• CAS No.: 102518-79-6
• Molecular Formula: C₁₅H₁₈N₂O
• Molecular Weight: 242.321
• Hs Code.: 29339900
• European Community (EC) Number: 600-320-6,634-239-2
• DSSTox Substance ID: DTXSID801115670
• Wikipedia: Huperzine_A
• NCI Thesaurus Code: C97271
• Metabolomics Workbench ID: 133445
• ChEMBL ID: CHEMBL394259
• Mol file: 102518-79-6.mol

Synonyms:huperzine A;huperzine A, (5alpha,9beta,11Z)-(-)-isomer;fordine

Chemical Property of (+/-)-Huperzine A

Chemical Property:

• Appearance/Colour: white to slight white crystaline powder
• Melting Point: 211-216 °C
• Refractive Index: 1.626
• Boiling Point: 505 °C at 760 mmHg
• PKA: 12.25±0.60(Predicted)
• Flash Point: 259.2 °C
• PSA: 58.88000
• Density: 1.2 g/cm³
• LogP: 2.69780
• Storage Temp.: −20°C
• Solubility.: insoluble in H2O; ≥12.12 mg/mL in DMSO; ≥23.13 mg/mL in EtOH
• XLogP3: 0
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 242.141913202
• Heavy Atom Count: 18
• Complexity: 551

Purity/Quality:

98%, ^*data from raw suppliers

(-)-Huperzine A ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T+
• Hazard Codes: T+
• Statements: 26/27/28-36/37/38
• Safety Statements: 26-36/37/39-45

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC=C1C2CC3=C(C1(CC(=C2)C)N)C=CC(=O)N3
• Isomeric SMILES: C/C=C/1\C2CC3=C(C1(CC(=C2)C)N)C=CC(=O)N3
• Recent ClinicalTrials: A Study of Huperzine A Injection in Reducing Postoperative Delirium in Elderly Patients Undergoing Non-cardiac Surgery
• Indications: Huperzine A is a potent reversible cholinesterase inhibitor, stronger than physostigmine, neostigmine and Tacrine. When used for myasthenia gravis, the effective rate reaches to 99%. Clinical trials show that the product is suitable for benign memory disorders. It can improve patients’ ability in directed memory, associative learning, image memory, meaningless figure recognition and portrait retrieval，and it also can enhance normal people’s ability in learning and memory. This product also can improve memory disorders that caused by dementia and organic pathologic changes in brain. Clinically, Huperzine A is applicable to the treatment of the following symptoms: 1. for the treatment and improvement of memory dysfunction in elder age, improving memory association function; for the memory deterioration caused by excessive use of the brain, improving work efficiency; 2. for memory function deterioration associated with neurasthenia; 3. for memory deterioration caused by cerebral vascular disorder; 4. for memory improvement of Alzheimer's disease, and it has significant effects on improving and restoring the patient's cognitive ability, memory function and abnormal emotion behaviors; 5. for the treatment of myasthenia gravis; 6. for improvement of disturbance of association, low cognitive function, memory deterioration that associated with schizophrenia; 7. for improvement of memory dysfunction associated with a variety of brain diseases and physical disorders. Huperzine A is purified from Chinese club moss and has been traditionally used in China for the treatment of swelling, fever, inflammation, blood disorders, and schizophrenia. It was mainly applied to age-related memory dysfunction and Alzheimer and has a good effect on improving memory function. It can be used to treat various types of Alzheimer's disease and also myasthenia gravis.
• Uses: Huperzine A is a new drug for the treatment of benign memory disorders that can effectively prevent cerebral neurasthenia in the middle-aged and elderly, restore cranial nerve function, and activate cranial neurotransmitters. Huperzine A can not only inhibite the activity of cholinesterase, but also improve cognitive function and ability of learning and memory through a variety of pharmacological mechanisms like effecting the system of free radicals, reducing expression levels of somatostatin, intracellular [Ca2+], glutamic acid content and increase calmodulin (CaM) and calmodulin messenger RNA (CaM mRNA). Huperzine A is a potential therapeutic agent for Alzheimer disease that reversible alkaloid inhibitor of AChE which crosses the blood-brain barrier. It reduces cell death induced by glutamate in primary cultures derived from forebrain, hippocampus, cortex and cere.In China, it is approved for use in the treatment of Alzheimer’s disease (AD). Huperzine A was classified as a dietary supplement by the FDA in 1997. As a nutraceutical, it is available in American health food stores or via the Internet, labeled as a memory aid.
• Description: Huperzine A is obtained from Huperzia serrata, which is the perennial fern. It shows activities in antipyretic, hemostasis, and dehumidification and is used for the treatment in folk of pneumonia, lung abscess, hematemesis, hematochezia, traumatic injury, etc.
• Physical properties: Appearance: white crystalline powder. Bitter with hygroscopicity. Solubility: easily soluble in chloroform, soluble in methanol and ethanol, and slightly soluble in water. Melting point: 211–216?°C.
• Clinical Use: Since 1994, huperzine A has been approved for clinical use in improving memory and cognitive impairment in old patients with memory loss and dementia. A large number of domestic clinical studies have found that huperzine A shows therapeutic effect on learning and cognitive dysfunction of vascular dementia, mental retardation, and schizophrenia patients with mild adverse reactions.

Technology Process of (+/-)-Huperzine A

There total 51 articles about (+/-)-Huperzine A 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: 80.0%

methyl ((5S,E)-11-ethylidene-2-methoxy-7-methyl-5,6,9,10-tetrahydro-5,9-methanocycloocta[b]pyridin-5-yl)carbamate (185741-46-2) → natural Huperzine A (92138-20-0,102518-79-6,103735-86-0,120786-18-7,130791-77-4,132435-40-6,116-28-9)

Guidance literature:

methyl ((5S,E)-11-ethylidene-2-methoxy-7-methyl-5,6,9,10-tetrahydro-5,9-methanocycloocta[b]pyridin-5-yl)carbamate; With trimethylsilyl iodide; In chloroform; for 6h; Reflux; Inert atmosphere;

With methanol; In chloroform; for 3h; Reflux; Inert atmosphere;

DOI:10.1021/ol9022408

Reference yield: 74.0%

(-)-huperzine A 2,3-dibenzoyl-D-tartaric acid salt → natural Huperzine A (92138-20-0,102518-79-6,103735-86-0,120786-18-7,130791-77-4,132435-40-6,116-28-9)

Guidance literature:

With sodium hydroxide; In water; for 1h; pH=9 - 9.3;

Reference yield: 60.0%

C16H16N2O2 → natural Huperzine A (92138-20-0,102518-79-6,103735-86-0,120786-18-7,130791-77-4,132435-40-6,116-28-9)

Guidance literature:

With sodium hydroxide; In tetrahydrofuran; at 80 ℃; for 36h;

upstream raw materials:

(1S,9S)-13-Eth-(E)-ylidene-5-methoxy-11-methyl-6-aza-tricyclo[7.3.1.0^2,7]trideca-2⁽⁷⁾,3,5,10-tetraene-1-carboxylic acid

methyl ((5S,E)-11-ethylidene-2-methoxy-7-methyl-5,6,9,10-tetrahydro-5,9-methanocycloocta[b]pyridin-5-yl)carbamate

(5S,9R)-methyl 2-methoxy-7-methyl-11-oxo-5,6,9,10-tetrahydro-5,9-methano-cycloocta[b]pyridine-5-carboxylate

(1S,9S)-5-Methoxy-11-methylene-13-oxo-6-aza-tricyclo[7.3.1.0^2,7]trideca-2⁽⁷⁾,3,5-triene-1-carboxylic acid methyl ester

Downstream raw materials:

(5R,9R,11E)-5-(3-phenylprop-2-en-1-ylideneamino)-11-ethylidene-5,6,9,10-tetrahydro-7-methyl-5,9-methanocycloocta[b]pyridin-2(1H)-one

natural Huperzine A

(+)-huperzine A

Refernces

• 1、 Koshiba, Takahiro,Yokoshima, Satoshi,Fukuyama, Tohru. "Total synthesis of (-)-huperzine A". . p. 5354 - 5356. Retrieved 2009.
• 2、 -. "Synthetic method of huperzine A". . . Retrieved 2019/05/15.
• 3、 -. "PREPARATION OF (-)-HUPERZINE A". Paragraph 0141. . Retrieved 2016/06/28.