Lovastatin

Base Information

• Chemical Name: Lovastatin
• CAS No.: 75330-75-5
• Deprecated CAS: 71949-96-7,74133-25-8,81739-26-6,74133-25-8,81739-26-6
• Molecular Formula: C24H36O5
• Molecular Weight: 404.547
• Hs Code.: 29322090
• European Community (EC) Number: 616-212-7,692-955-0
• NSC Number: 758662,633781
• UNII: 9LHU78OQFD
• DSSTox Substance ID: DTXSID5020784
• Nikkaji Number: J22.276C
• Wikipedia: Lovastatin
• Wikidata: Q417740
• NCI Thesaurus Code: C620
• RXCUI: 6472
• Pharos Ligand ID: 3ZS5RF3ZSR46
• Metabolomics Workbench ID: 42629
• ChEMBL ID: CHEMBL503
• Mol file: 75330-75-5.mol

Synonyms:1 alpha-Isomer Lovastatin;6 Methylcompactin;6-Methylcompactin;alpha-Isomer Lovastatin, 1;Lovastatin;Lovastatin, (1 alpha(S*))-Isomer;Lovastatin, 1 alpha Isomer;Lovastatin, 1 alpha-Isomer;Mevacor;Mevinolin;MK 803;MK-803;MK803;Monacolin K

Chemical Property of Lovastatin

Chemical Property:

• Appearance/Colour: White solid
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 175 °C
• Refractive Index: 320 ° (C=0.5, CH3CN)
• Boiling Point: 559.2 °C at 760 mmHg
• PKA: 13.49±0.40(Predicted)
• Flash Point: 185.3 °C
• PSA: 72.83000
• Density: 1.12 g/cm³
• LogP: 4.19550
• Storage Temp.: 2-8°C
• Solubility.: ethanol: soluble9.80-10.20mg/mL, clear, colorless to faintly yel
• Water Solubility.: 0.0004 mg/mL at 25 ºC
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 7
• Exact Mass: 404.25627424
• Heavy Atom Count: 29
• Complexity: 666

Purity/Quality:

2%,5%, ^*data from raw suppliers

Lovastatin ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 22-24/25-36/37/39-26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antilipemic Agents
• Canonical SMILES: CCC(C)C(=O)OC1CC(C=C2C1C(C(C=C2)C)CCC3CC(CC(=O)O3)O)C
• Isomeric SMILES: CC[C@H](C)C(=O)O[C@H]1C[C@H](C=C2[C@H]1[C@H]([C@H](C=C2)C)CC[C@@H]3C[C@H](CC(=O)O3)O)C
• Recent ClinicalTrials: An Efficacy and Safety Study of Alirocumab in Children and Adolescents With Heterozygous Familial Hypercholesterolemia
• Recent EU Clinical Trials: Improvement of synaptic plasticity and cognitive function in RAS pathway disorders
• Recent NIPH Clinical Trials: effect for sympathetic nerve activity of statin for heart failure with preserved ejection fraction
• Uses: It is used for treating heterozygous familial and non familial, secondary hyperlipidemia, namely diabetes and nephrotic syndrome secondary hypercholesterolemia. It can reduce the level of TC, LF, LDL-C, and increase the level of HDL-C, reduce the risk of myocardial infarction, unstable angina and the necessity for percutaneous transluminal coronary angioplasty (PTCA). 1. It is as a novel lipid regulating drugs-The inhibitor of HMG-CoA (β-hydroxy, β-methyl-glutaryl coenzyme A) reductase. It can significantly reduced serum total cholesterol level. After oral administration, it is hydrolyzed into corresponding β-hydroxy acid by 3-hydroxy-3-methylglutaryl coenzyme A reductase, and thus inhibiting the cholesterol biosynthesis. It is clinically used for treating heterozygous familial hypercholesterolemia, severe or mild hypercholesterolemia and light. It can also as an ancillary drug of dietary treatment for reducing the levels of excessively cholesterol and low-density protein cholesterol. 2. It is a cardiovascular systematic drug which can prevent the development of atherosclerosis and reduce the risk of myocardial infarction. An antihypercholesterolemic agent. A fungal metabolite, which is a potent inhibitor of HMG-CoA reductase Lovastatin (mevinolin) is a metabolite first isolated from Monascus ruber and later found in several other fungal species. Lovastatin is a potent inhibitor of HMG-CoA. HMG-CoA reductase is the rate-controlling enzyme of the mevalonate pathway, responsible for the biosynthesis of cholesterol. Lovastatin was developed as a drug as a hypolipemic agent. anti-hyperlipoproteinemic, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor Cardiovascular
• Production method: Lovastatin is produced by fermentation. Available species include: 1. Monescus ruber; 2. Monescus purpureus; 3. Monescus pilosus; 4. Aspergillus terreus; 5. Penicillium Citrunum. When using Monescus ruber as the strain, the culture condition is as follows: 6% glucose, 2.5% peptone, 0.5% corn syrup, and 0.5% ammonium chloride. Strain in broth is grown in aerobic conditions at 28 °C for 10d. Filter and take 5 L filtrate; Use ethyl acetate (pH 3.0) for extraction. The extract was vacuum concentrated to dryness with the residue being dissolved in 100ml of benzene. Insoluble substances are further removed by filtration, wash the filtrate with 100ml 5% aqueous sodium carbonate twice, and then stir together with 100 mL 0.2mol/L sodium hydroxide solution at room temperature for 2h. The aqueous layer is collected, and be treated with 6 mol/L hydrochloric acid for adjusting pH to 3.0; Extract for twice with 100ml of ethyl acetate. Combine the extract and evaporate to dryness to give 260 mg oil. Dissolve oil-like product in a small amount of benzene; the obtained crystal is further re-crystallized by the mixture of acetone and water to give 87 mg of colorless lovastatin crystals, m.p. 157~159 °C (decomposition), [α] D23 + 307.6 ° (C = 1, methanol).
• Description: Lovastatin is an orally-active hypocholesterolemic useful in the treatment of familial hypercholesterolemia. The drug acts by inhibiting the HMG-CoA reductase-catalyzed rate limiting step of cholesterol biosynthesis. While treatment with lovastatin leads to significant reductions in total and LDL cholesterol, its effect on atherosclerosis or coronary heart disease has not been established.
• Physical properties: Appearance: White, nonhygroscopic crystalline powder. Solubility: Insoluble in water (0.0004?mg/mL); sparingly soluble in ethanol, methanol, isobutanol, isopropanol, acetonitrile, n-propanol; soluble in acetone, N-dimethylformamide; freely soluble in chloroform. Melting point: 174.5?°C. Specific optical rotation: 25?°C for D (sodium) line, +323° (concentration 0.5? g in 100? ml acetonitrile). Stability: Lovastatin is sensitive to light. Following exposure to extreme light conditions, the drug is stable for 24?h or 1?month when exposed to UV (approximately 3230 lux) or fluorescent (approximately 10,764 lux) light, respectively, at 28?°C in air.
• Indications: Hypercholesterolemia, combined hyperlipidemia.
• Therapeutic Function: Antihyperlipidemic
• Clinical Use: The primary uses of lovastatin are the treatment of dyslipidemia and the prevention of cardiovascular disease. It is recommended to be used only when other approaches such as diet, exercise, and weight reduction have not improved the cholesterol profile (“Lovastatin”. The American Society of Health-System Pharmacists. Retrieved 3 April 2011.). Lovastatin is useful in treating hypercholesterolemia and combined hyperlipidemia. However, lovastatin is not effective in treatment of receptornegative homozygous familial hypercholesterolemia .

Technology Process of Lovastatin

There total 27 articles about Lovastatin 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: 94.0%

6(R)-<2-<1,2,6,7,8,8a(R)-Hexahydro-2(S),6(R)-dimethyl-8(S)-<<2(S)-methylbutyryl>oxy>-1(S)-naphtyl>ethyl>-3,4,5,6-tetrahydro-4(R)-<(tert-butyldimethylsilyl)oxy>-2H-pyran-2-one (79691-11-5,82978-03-8) → lovastatin (75330-75-5,79952-44-6)

Guidance literature:

With hydrogen fluoride; In acetonitrile; at 25 ℃; for 1.4h;

DOI:10.1016/S0040-4039(00)61717-3

Reference yield: 78.2%

ammonium mevinolinic acid (77550-67-5) → lovastatin (75330-75-5,79952-44-6)

Guidance literature:

ammonium mevinolinic acid; With phosphoric acid; In toluene; butanone; at 20 - 82 ℃; for 2 - 2.5h;

With triethylamine; In water; toluene; butanone; at 20 ℃;

Reference yield: 77.0%

*),3α,7β,8β(2S*,4S*,6RS*),8aβ>>-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-<2-(tetrahydro-4,6-dihydroxy-2H-pyran-2-yl)ethyl>-1-naphthalenyl 2-methylbutanoate (117020-90-3,117066-28-1) → lovastatin (75330-75-5,79952-44-6)

Guidance literature:

With Celite; silver carbonate; In toluene; at 85 - 95 ℃; for 1h;

DOI:10.1021/ja00164a024

upstream raw materials:

*),3α,7β,8β(2S^*,4S^*,6RS^*),8aβ>>-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-<2-(tetrahydro-4,6-dihydroxy-2H-pyran-2-yl)ethyl>-1-naphthalenyl 2-methylbutanoate

6(R)-<2-<1,2,6,7,8,8a(R)-Hexahydro-2(S),6(R)-dimethyl-8(S)-<<2(S)-methylbutyryl>oxy>-1(S)-naphtyl>ethyl>-3,4,5,6-tetrahydro-4(R)-<(tert-butyldimethylsilyl)oxy>-2H-pyran-2-one

(S)-2-Methyl-butyric acid (1S,3S,7R,8R,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-3,7-dimethyl-6-oxo-1,2,3,4,6,7,8,8a-octahydro-naphthalen-1-yl ester

(S)-2-Methyl-butyric acid (1S,4S,6S,7R,8S,8aR)-4-chloro-6-formyloxy-8-[2-((2R,4R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-7-methyl-1,2,3,4,6,7,8,8a-octahydro-naphthalen-1-yl ester

Downstream raw materials:

6(R)-<2-<1,2,6,7,8,8a(R)-Hexahydro-2(S),6(R)-dimethyl-8(S)-<<2(S)-methylbutyryl>oxy>-1(S)-naphtyl>ethyl>-3,4,5,6-tetrahydro-4(R)-<(tert-butyldimethylsilyl)oxy>-2H-pyran-2-one

6(R)-<2-<1,2,6,7,8,8a(R)-Hexahydro-2(S),6(R)-dimethyl-8(S)-<<2(S)-methylbutyryl>oxy>-1(S)-naphthyl>ethyl>-3,4,5,6-tetrahydro-4(R)-<(phenyldimethylsilyl)oxy>-2H-pyran-2-one

acetone

tert-butyl alcohol

Refernces

• 1、 Balraj, Janani,Jairaman, Karunyadevi,Kalieswaran, Vidhya,Jayaraman, Angayarkanni. "Bioprospecting lovastatin production from a novel producer Cunninghamella blakesleeana". . . Retrieved 2018.
• 2、 -. "PROCESS FOR THE PURIFICATION OF LOVASTATIN". Page/Page column 5-8. . Retrieved 2008/06/13.