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75330-75-5

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75330-75-5 Usage

a cholesterol lowering agent

Lovastatin is a cholesterol lowering agent isolated from a strain of Aspergillus terreus. Lovastatin is a white, nonhygroscopic crystalline powder that is insoluble in water and sparingly soluble in ethanol, methanol, and acetonitrile. After oral ingestion, lovastatin, which is an inactive lactone, is hydrolyzed to the corresponding β-hydroxyacid form. This is a principal metabolite and an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate limiting step in the biosynthesis of cholesterol.

General description

Lovastatin is a hexahydro naphthalene ester isolated from Aspergillus terreus broth. It is an inactive lactone only yielding activity upon hydrolysis after oral administration. It has a strong competitive inhibition on the HMG-CoA reductase in the liver. HMG-CoA reductase is rate-limiting enzyme for de novo cholesterol synthesis in vivo. The inhibition of the enzyme can block the conversion of HMG-CoA to methacrylic acid, causing significant reduction in cholesterol synthesis, and leading to increased expression of the liver LDL receptor which promotes the plasma LDL-C clearance. The reduction of cholesterol synthesis can also cause reduced synthesis of liver ApoB100, thus causing that reduction of VLDL synthesis. Clinical observations show that it has a good effect of lowering of plasma total cholesterol and LDLC on hypercholesterolemia caused by various kinds of reasons such as heterozygous familial hypercholesterolemia, polygenic hypercholesterolemia, and diabetes or kidney disease syndrome. Statins are the secondary metabolites of filamentous fungi. It is capable of selectively inhibiting the activity of HMG coenzyme A (HMG-CoA) reductase and blocking cholesterol biosynthesis, which is due to the similarity of its acid structure with HMG-CoA. These drugs currently used in humans (statin drugs, statins) are mainly either natural or synthetic statins. Natural statins include lovastatin, mevastatin, Pravastatin and simvastatin. Lovastatin is produced by the fermentation of Aspergillus terreus); mevastatin is produced through the fermentation of penicillium citrinum and further conversion by streptomyces carbophilus; Simvastatin is made by semi-synthesis (chemically modified side chains) through lovastatin. Synthetic statins include fluvastatin, cerivastatin and atorvastatin.

Structure of statin compound

Natural statin compounds is has very similar structure with each other. They have the same poly-ketone portion of hydroxy-hexahydro-cyclic with different side chains attached to C8 (R1) and C6 (R2) bits. R1 of lovastatin is methylbutyryl, R2 is 6-α-methyl; mevastatin has no 6-position methyl. Natural statin compounds are all in the form of lactone. They need to be hydrolyzed to acidic form before becoming active. Fully synthetic statin compound, although is structurally different from the natural statins but still have a lactone ring-opening portion which is the common structure of all statins which is responsible for its competitive inhibition on HMG-CoA reductase.

Active Mechanism

There are two main sources of plasma cholesterol; one is exogenous cholesterol absorbed from dietary; the other is form endogenous biosynthesis in vivo, wherein the endogenous cholesterol accounts for 2/3 of the total cholesterol which makes it the primary target of lipid-lowering therapy. Cholesterol biosynthetic pathway in vivo starts from acetyl coenzyme. HMG-CoA is first generated by the HMG-CoA synthase, and then reduced into mevalonate by HMG-CoA reductase; then went through phosphorylation to generates farnesyl pyrophosphate; further reduced to turtle-ene which finally converts to cholesterol through 20 steps including lanosterol and chain sterols, wherein the conversion of HMG-CoA to mevalonate via HMG-CoA reductase is the rate-limiting step in cholesterol synthesis, making HMG-CoA reductase is the rate-limiting enzyme. Therefore, the inhibition of HMG-CoA reductase activity can reduce the formation of endogenous cholesterol. A part of lovastatin structure, 3,5-dihydroxy heptanoic acid is quite similar with HMG-CoA and its inhibitory effect is 10,000 times higher than HMG-CoA intermediate so that it can competitively bind with HMG-CoA reductase to inhibit the synthesis of mevalonate lactone, and thus effectively reducing the speed of cholesterol synthesis in liver cells and ultimately inhibiting the biosynthesis of endogenous cholesterol.

Medicinal Value

1. Regulation of Lipid Metabolism Lovastatin inhibit the endogenous cholesterol synthesis by inhibiting its rate-limiting enzyme, HMG-CoA reductase. It lowers the intracellular cholesterol level and increases the number of LDL receptors on the cell surface through feedback action, thus accelerating the uptake and degradation of LDL particles in blood circulation and reducing the contents of total cholesterol and very low density lipoprotein (VLDL), LDL and triglycerides. Since the conversion of HMG-CoA into mevalonate is an early step in the cholesterol biosynthetic pathway, the use of lovastatin doesn’t cause accumulation of potentially toxic cholesterol-class substances. Moreover, HMG-CoA can quickly reverse metabolized to acetyl coenzyme A and participate in other biosynthetic pathways in vivo. The inhibition is incomplete, reversible and has dose-effect dependence. The therapeutic doses does not affect the amount of cholesterol required for normal function of cell membranes, therefore, lovastatin has a significant lipid-lowering effects with small side effects. Overall, lovastatin takes effect mainly by the following aspects: (1) competitive inhibition of HMG-CoA reductase activity, reduction of endogenous cholesterol synthesis; (2) Increase the expression of LDL receptor in liver cells, enhance receptor-mediated plasma LDL clearance rate; (3) inhibit the migration and proliferation of smooth muscle cell; (4) reduce the assembly and secretion of lipoproteins in the liver. 2. Non-lipid function In addition to its significant lipid-lowering effect, lovastatin can also improve endothelial function, promote the synthesis of nitric oxide synthase (eNOS), thereby increasing the synthesis and release of NO, which is crucial for the maintenance of normal human pulmonary artery tension and reversing the hypoxia-induced pulmonary vasoconstriction and vascular remodeling. In addition, lovastatin has anti-inflammatory and anti-proliferative effect. It can inhibit the mesangial cell proliferation and secretion of extracellular matrix for achieving the purpose of alleviating glomerulosclerosis. The above information is edited by the lookchem of Dai Xiongfeng.

Biosynthesis

Acetate and propionic acid are went through condensation, reduction, dehydration to form diketone intermediate, the process is catalyzed by keto reductase (KR), alcohol reductase (ER) or methyltransferase (Met) and repeated once to form hexanone followed by the enzymatic Diels-Alder reaction to produce the skeleton of dicyclo-decalin. The dicyclo adduct is further extended into nine-ketone which is releases from polyketone synthase (PKS) to form 4a, 5-dihydro Monacolin L, 4a, 5-dihydro Monacolin L when can be converted to hydroxy-3,5-dihydro-3α-Monacolin L in the presence of molecular oxygen. The latter one can be spontaneously dehydrogenated to be converted into Monacolin L. Monacolin L, in the presence of molecular oxygen, has its C-8 be hydroxylated to become Mo Lin J. Inhibitory tests using metyrapone, carbon monoxide, and thiol agents proved that the enzyme involved in this reaction is a single oxygen dioxygenase. Monacolin J is esterified into lovastatin via (2R)-methylbutyrate. Figure 1 the synthesis route of lovastatin

Uses

Different sources of media describe the Uses of 75330-75-5 differently. You can refer to the following data:
1. 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).
2. 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.
3. An antihypercholesterolemic agent. A fungal metabolite, which is a potent inhibitor of HMG-CoA reductase
4. 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.
5. anti-hyperlipoproteinemic, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor
6. Cardiovascular

Metabolism

This product goes through gastrointestinal absorption after oral administration, F is 30%, and increases to 50% when taken together with food F; Tmax: 2~4h; T1/2: 3h, the original drug and metabolites PPB> 95%; it can penetrate the blood brain barrier and the placental barrier. It mainly metabolized by liver with the metabolic enzyme being CYP3A4. 60%~83% of it is excreted via bile, and 10% to 13% via the urinary excretion.

Precautions

Patients of being allergic to this drug, active hepatitis or unexplained elevated serum transaminases are forbidden to use, and so are the pregnant and lactating women. Patients of renal insufficiency or renal transplant should take with caution. Drugs which can inhibit the CYP3A4 enzyme such as macrolide antibiotics, benzodiazepines class, phenoxy acids, and niacin cholesterol lowering agents, cimetidine and a large grapefruit juice can all increase the plasma concentration of lovastatin and its metabolites and increase the risk of rhabdomyolysis. Check the liver function after treatment or increasing the dose for 6 to 12 weeks, and check once every six months in future. Check CPK in cases such as muscle pain symptoms, and stop using if CPK level reaches a level 10 times of the normal level.

Adverse reaction

Adverse reactions are mild, rate, transient, such as headache, fatigue, gastrointestinal reactions (bloating, constipation, diarrhea, abdominal pain, nausea, indigestion, etc.), and skin rash. In occasion case, there are occurrence of decrease in white blood cells, thrombocytopenia, and abnormal liver function.

Chemical property

White crystals, melting point: 174.5 °C (nitrogen). [α] D25 + 323 °(C = 0.5g, dissolved in 100ml acetonitrile). UV absorption maximum (methanol): 229,237,246nm (three ears 550, 6250, 430). Solubility at RT (mg /mL): acetone: 47, acetonitrile: 28, n-butanol: 7, i-butanol: 14, chloroform: 350, dimethylformamide: 90, ethanol: 16, methanol: 28, n-octanol: 2, n-propanol: 11, i-propanol: 20, water 0.4 × 10-3. Acute toxicity LD50 in mice (mg/kg): > 1000 Oral.

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.

Chemical Properties

White Solid

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.

Originator

Merck (USA)

History

Statins are the most extensively used class of lipid-lowering medication. Lovastatin is the second statin discovered by scientists.Later, the official name lovastatin was established. The activity of lovastatin is much better than compactin.In July 1982, lovastatin showed dramatic effects on lowering LDL cholesterol in patients with severe hypercholesterolemia who were unresponsive to the existedmedicines, with very few adverse reactions .

Indications

Hypercholesterolemia, combined hyperlipidemia.

Manufacturing Process

1) Coniothyrium fuckelii ATCC 74227 was grown in a sterilizable fermentation apparatus with a volume of 15 L. The apparatus was equipped with an agitator, aerator, pH control system, dissolved oxygen control system, and a pump and feed system designed to allow the sterile addition of glucose solutions. The pH was controlled by the automatic addition of ammonium hydroxide or phosphoric acid to maintain the pH of the culture medium constant at 5.0. Periodically, the fermentation broth was sampled, measured for glucose concentration and an addition of glucose was made manually to maintain a concentration of glucose at approximately 2-5 g/L. After 192 hours of growth under these conditions, the concentration of biomass reached 65 g/L and the concentration of Lovastatin reached 102 mg/L. 2) A further medium for the growth of Coniothyrium fuckelii ATCC 74227, has the following composition: Glucose 12%, Peptone 1%, (NH4)2SO4 0.4%, MgSO4 · 7H2O 0.05%, P 2000 0.1% (Antifoam agent), L-isoleucine 0.2-1.5%, L-aspartic acid 0.2-1.5%. The fermentation was carried out as before. With this medium, the lovastatin concentration was 430 mg/L.

Brand name

Altoprev (Andrx); Mevacor (Merck).

Therapeutic Function

Antihyperlipidemic

General Description

Lovastatin, 2-methylbutanoic acid 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester, mevinolin,MK-803 (Mevacor) (formerly called mevinolin), is a potentinhibitor of HMG-CoA. The drug was obtained originallyfrom the fermentation products of the fungi Aspergillus terreusand Monascus ruber. Lovastatin was one of two originalHMG-CoA reductase inhibitors. The other drug, mevastatin(formerly called compactin), was isolated from cultures ofPenicillium cillium citrum. Mevastatin was withdrawn fromclinical trials because it altered intestinal morphology in dogs.This effect was not observed with lovastatin. For inhibitoryeffects on HMG-CoA reductase, the lactone ring must be hydrolyzedto the open-ring heptanoic acid.

Biological Activity

Potent, competitive inhibitor of HMG-CoA reductase (K i = 0.6 nM) therefore decreases cholesterol biosynthesis, in vitro and in vivo . Decreases CDK2, 4, 6 and cyclin E levels and induces G1 arrest and apoptosis in tumor cell lines in vitro .

Pharmacology

Lovastatin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase), an enzyme that catalyzes the conversion of HMG-CoA to mevalonate , a rate-determining step of cholesterol biosynthesis. Lovastatin is metabolized as a prodrug into an active form, lovastatin acid. Lovastatin acid is a reversible competitive inhibitor for HMG-CoA.However, the reduction in plasma cholesterol by statins is not only due to reduction in cholesterol biosynthesis. .In addition to their lipid-lowering properties, statins produce several nonlipidrelated properties, include decreasing levels of high-sensitivity C-reactive protein (hsCRP), improving endothelial function, reducing inflammation at the site of the atherosclerotic plaque, inhibiting platelet aggregation, anticoagulant, etc. .

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 .

Side effects

Lovastatin's common side effects are listed in approximately descending order of occurrence frequency: creatine phosphokinase elevation, flatulence, abdominal pain, constipation, diarrhea, muscle aches or pains, nausea, indigestion, weakness, blurred vision, rash, dizziness, and muscle cramps. As with all statin drugs, it can rarely cause myopathy, hepatotoxicity (liver damage), dermatomyositis, or rhabdomyolysis.

References

1) Alberts et al. (1988), Discovery, biochemistry and biology of lovastatin;? Am. J. Cardiol., 62 10J 2) Hancock et al. (1989), All ras proteins are polyisoprenylated but only some are palmitoylated;? Cell, 57 1167 3) Park et al. (1999), Lovastatin-induced inhibition of HL-60 cell proliferation via cell cycle arrest and apoptosis;? Anticancer Res., 19 3133 4) Vilimanovich et al. (2015), Statin-mediated inhibition of cholesterol synthesis induces cytoprotective autophagy in human leukemic cells;? Eur. J. Pharmacol., 765 415 5) Tobert et al. (1988), Efficacy and long-term adverse effect pattern of lovastatin;? Am. J. Cardiol., 62 28J

Check Digit Verification of cas no

The CAS Registry Mumber 75330-75-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 7,5,3,3 and 0 respectively; the second part has 2 digits, 7 and 5 respectively.
Calculate Digit Verification of CAS Registry Number 75330-75:
(7*7)+(6*5)+(5*3)+(4*3)+(3*0)+(2*7)+(1*5)=125
125 % 10 = 5
So 75330-75-5 is a valid CAS Registry Number.
InChI:InChI=1/C24H36O5/c1-5-15(3)24(27)29-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-19-12-18(25)13-22(26)28-19/h6-7,10,14-16,18-21,23,25H,5,8-9,11-13H2,1-4H3/t14-,15-,16-,18+,19+,20-,21-,23?/m0/s1

75330-75-5 Well-known Company Product Price

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  • TCI America

  • (L0214)  Lovastatin  >98.0%(HPLC)

  • 75330-75-5

  • 5g

  • 290.00CNY

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  • TCI America

  • (L0214)  Lovastatin  >98.0%(HPLC)

  • 75330-75-5

  • 25g

  • 940.00CNY

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  • Alfa Aesar

  • (H52792)  Lovastatin, 97%   

  • 75330-75-5

  • 5g

  • 811.0CNY

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  • Alfa Aesar

  • (H52792)  Lovastatin, 97%   

  • 75330-75-5

  • 25g

  • 3241.0CNY

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75330-75-5SDS

SAFETY DATA SHEETS

According to Globally Harmonized System of Classification and Labelling of Chemicals (GHS) - Sixth revised edition

Version: 1.0

Creation Date: Aug 12, 2017

Revision Date: Aug 12, 2017

1.Identification

1.1 GHS Product identifier

Product name lovastatin

1.2 Other means of identification

Product number -
Other names LOVASTIN

1.3 Recommended use of the chemical and restrictions on use

Identified uses For industry use only.
Uses advised against no data available

1.4 Supplier's details

1.5 Emergency phone number

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More Details:75330-75-5 SDS

75330-75-5Synthetic route

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

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

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
With hydrogen fluoride In acetonitrile at 25℃; for 1.4h;94%
With hydrogen fluoride In acetonitrile at 0℃; for 5h;77%
With tetrabutyl ammonium fluoride; acetic acid In tetrahydrofuran
With tetrabutyl ammonium fluoride; acetic acid In tetrahydrofuran for 18h; Ambient temperature;
ammonium mevinolinic acid

ammonium mevinolinic acid

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Stage #1: ammonium mevinolinic acid With phosphoric acid In toluene; butanone at 20 - 82℃; for 2 - 2.5h;
Stage #2: With triethylamine In water; toluene; butanone at 20℃;
78.2%
With sulfuric acid In acetonitrile at -22 - -17℃; for 0.5h;
Conditions
ConditionsYield
With Celite; silver carbonate In toluene at 85 - 95℃; for 1h;77%
With Celite; toluene; silver carbonate In toluene at 90℃; for 1h;77%
lovastatin acid
75225-51-3, 137767-34-1

lovastatin acid

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
With phosphoric acid In water; toluene at 20 - 55℃; for 19h; pH=3.5; Product distribution / selectivity;76.12%
With trifluoroacetic acid In ethyl acetate for 0.166667h;
(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
85614-12-6

(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

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 0.25 h / 0 °C
2: 70 percent / Pd(OAc)2, HCOOH, Bu3N, Ph3P / dimethylformamide / 1 h / 60 °C
3: 94 percent / 48 percent HF / acetonitrile / 1.4 h / 25 °C
View Scheme
(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
153079-18-6

(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

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 9 steps
1: imidazole / acetonitrile / 25 °C
2: Ti(OiPr)4 / propan-2-ol / 0.5 h / 60 °C
3: 92 percent / PDC / toluene / 0.33 h / 80 °C
4: 78 percent / AgOTf/2,6-di-tert-butyl-4-methylpyridine / 24 h / 25 °C
5: 65 percent / tetrahydrofuran / -78 °C
6: H+ / CHCl3
7: 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 0.25 h / 0 °C
8: 70 percent / Pd(OAc)2, HCOOH, Bu3N, Ph3P / dimethylformamide / 1 h / 60 °C
9: 94 percent / 48 percent HF / acetonitrile / 1.4 h / 25 °C
View Scheme
2-methyl-butyric acid 8-{2-[4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-7-methyl-6-oxo-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl ester
153079-17-5

2-methyl-butyric acid 8-{2-[4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-7-methyl-6-oxo-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl ester

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: 65 percent / tetrahydrofuran / -78 °C
2: H+ / CHCl3
3: 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 0.25 h / 0 °C
4: 70 percent / Pd(OAc)2, HCOOH, Bu3N, Ph3P / dimethylformamide / 1 h / 60 °C
5: 94 percent / 48 percent HF / acetonitrile / 1.4 h / 25 °C
View Scheme
(S)-2-Methyl-butyric acid (1S,4S,6S,7R,8S,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-4-chloro-6-hydroxy-7-methyl-1,2,3,4,6,7,8,8a-octahydro-naphthalen-1-yl ester
153079-20-0

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

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1: 92 percent / PDC / toluene / 0.33 h / 80 °C
2: 78 percent / AgOTf/2,6-di-tert-butyl-4-methylpyridine / 24 h / 25 °C
3: 65 percent / tetrahydrofuran / -78 °C
4: H+ / CHCl3
5: 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 0.25 h / 0 °C
6: 70 percent / Pd(OAc)2, HCOOH, Bu3N, Ph3P / dimethylformamide / 1 h / 60 °C
7: 94 percent / 48 percent HF / acetonitrile / 1.4 h / 25 °C
View Scheme
(S)-2-Methyl-butyric acid (1S,3R,7R,8R,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-3,7-dimethyl-6-oxo-1,2,3,5,6,7,8,8a-octahydro-naphthalen-1-yl ester
153079-22-2

(S)-2-Methyl-butyric acid (1S,3R,7R,8R,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-3,7-dimethyl-6-oxo-1,2,3,5,6,7,8,8a-octahydro-naphthalen-1-yl ester

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: H+ / CHCl3
2: 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 0.25 h / 0 °C
3: 70 percent / Pd(OAc)2, HCOOH, Bu3N, Ph3P / dimethylformamide / 1 h / 60 °C
4: 94 percent / 48 percent HF / acetonitrile / 1.4 h / 25 °C
View Scheme
(S)-2-Methyl-butyric acid (1S,4S,7R,8R,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-4-chloro-7-methyl-6-oxo-1,2,3,4,6,7,8,8a-octahydro-naphthalen-1-yl ester
153079-21-1

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

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: 78 percent / AgOTf/2,6-di-tert-butyl-4-methylpyridine / 24 h / 25 °C
2: 65 percent / tetrahydrofuran / -78 °C
3: H+ / CHCl3
4: 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 0.25 h / 0 °C
5: 70 percent / Pd(OAc)2, HCOOH, Bu3N, Ph3P / dimethylformamide / 1 h / 60 °C
6: 94 percent / 48 percent HF / acetonitrile / 1.4 h / 25 °C
View Scheme
(S)-2-Methyl-butyric acid (1S,4S,6S,7R,8S,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-4-chloro-6-formyloxy-7-methyl-1,2,3,4,6,7,8,8a-octahydro-naphthalen-1-yl ester
153079-19-7

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

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1: Ti(OiPr)4 / propan-2-ol / 0.5 h / 60 °C
2: 92 percent / PDC / toluene / 0.33 h / 80 °C
3: 78 percent / AgOTf/2,6-di-tert-butyl-4-methylpyridine / 24 h / 25 °C
4: 65 percent / tetrahydrofuran / -78 °C
5: H+ / CHCl3
6: 2,6-di-tert-butyl-4-methylpyridine / CH2Cl2 / 0.25 h / 0 °C
7: 70 percent / Pd(OAc)2, HCOOH, Bu3N, Ph3P / dimethylformamide / 1 h / 60 °C
8: 94 percent / 48 percent HF / acetonitrile / 1.4 h / 25 °C
View Scheme
(S)-2-Methyl-butyric acid (1S,3R,7R,8R,8aR)-8-{2-[(2R,4R)-4-(tert-butyl-dimethyl-silanyloxy)-6-oxo-tetrahydro-pyran-2-yl]-ethyl}-3,7-dimethyl-6-trifluoromethanesulfonyloxy-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester
153079-24-4

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

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 70 percent / Pd(OAc)2, HCOOH, Bu3N, Ph3P / dimethylformamide / 1 h / 60 °C
2: 94 percent / 48 percent HF / acetonitrile / 1.4 h / 25 °C
View Scheme
<1S-<1α(R*),3α,7β,8β(4S*,6R*),8aβ>>-1,2,3,7,8,8a-hexahydro-8-<2-<6-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-3,7-dimethyl-1-naphthalenyl 2-methylbutanoate
116996-47-5

<1S-<1α(R*),3α,7β,8β(4S*,6R*),8aβ>>-1,2,3,7,8,8a-hexahydro-8-<2-<6-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-3,7-dimethyl-1-naphthalenyl 2-methylbutanoate

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
2: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
3: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 3 steps
1: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
2: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
3: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<1S-<1α(R*),3α,7β,8β(4S*,6R*),8aβ>>-8-<2-<2,2-dimethyl-6-(2-oxoethyl)-1,3-dioxan-4-yl>ethyl>-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2-methylbutanoate
116996-48-6

<1S-<1α(R*),3α,7β,8β(4S*,6R*),8aβ>>-8-<2-<2,2-dimethyl-6-(2-oxoethyl)-1,3-dioxan-4-yl>ethyl>-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2-methylbutanoate

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
2: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 2 steps
1: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
2: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<4R-<4α*(1R*,2S*)>6α>>-6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-α-(2-methyl-5-oxo-3-cyclohexen-1-yl)-1,3-dioxane-4-propanal
116996-31-7, 126060-10-4

<4R-<4α*(1R*,2S*)>6α>>-6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-α-(2-methyl-5-oxo-3-cyclohexen-1-yl)-1,3-dioxane-4-propanal

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 11 steps
1: 50 percent / (Ph3P)3RhCl / toluene; acetonitrile / 2.5 h / Heating
2: 1.) LDA / 1.)Et2O, -78 deg C, 45 min; 2.) -78 deg C, 10 min
3: 85 percent / i-Pr2NH / DMAP / diethyl ether / 24 h / Ambient temperature
4: 1.) O3; 2.) Ph3P / 1.) CH2Cl2, -78 deg C; 2.) -78 deg C -> r.t., 3 h
5: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 4 h
6: 1.) Bu4NF ; 2.) t-BuPh2SiCl, Et3N / 2.) DMAP / 1.) THF, r.t., 22 h; 2.) CH2Cl2, r.t., 24 h
7: 97 percent / Et3N / DMAP / CH2Cl2 / 88 h / Ambient temperature
8: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
9: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
10: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
11: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 12 steps
1: 50 percent / (Ph3P)3RhCl / toluene; benzonitrile / 2.5 h / Heating
2: 1.) lithium diisopropylamide (LDA) / 1.) ether, -78 deg C, 45 min, 2.) -78 deg C, 10 min
3: 85 percent / diisopropylamine, 4-(dimethylamino)pyridine (DMAP) / diethyl ether / 24 h / Ambient temperature
4: 85 percent / 1.) O3, 2.) triphenylphosphine / CH2Cl2 / 1.) -78 deg C, 5 min, 2.) 3 h
5: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 4 h
6: 99 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 22 h / Ambient temperature
7: Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 24 h / Ambient temperature
8: 91 percent / 4-(dimethylamino)pyridine (DMAP), triethylamine / CH2Cl2 / 72 h / Ambient temperature
9: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
10: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
11: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
12: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<1S-<1α,3α,7β,8β(4S*,6R*),8aβ>>-8-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-1-naphthalenol
116996-45-3

<1S-<1α,3α,7β,8β(4S*,6R*),8aβ>>-8-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-1-naphthalenol

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: 97 percent / Et3N / DMAP / CH2Cl2 / 88 h / Ambient temperature
2: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
3: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
4: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
5: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 5 steps
1: 91 percent / 4-(dimethylamino)pyridine (DMAP), triethylamine / CH2Cl2 / 72 h / Ambient temperature
2: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
3: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
4: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
5: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<4S-<4α,5α(4S*,4S*),6β(1R*,3S*)>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-6-(1-hydroxy-3-methyl-4-pentenyl)-4-methyl-2-cyclohexen-1-one
117020-88-9

<4S-<4α,5α(4S*,4S*),6β(1R*,3S*)>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-6-(1-hydroxy-3-methyl-4-pentenyl)-4-methyl-2-cyclohexen-1-one

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 9 steps
1: 85 percent / i-Pr2NH / DMAP / diethyl ether / 24 h / Ambient temperature
2: 1.) O3; 2.) Ph3P / 1.) CH2Cl2, -78 deg C; 2.) -78 deg C -> r.t., 3 h
3: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 4 h
4: 1.) Bu4NF ; 2.) t-BuPh2SiCl, Et3N / 2.) DMAP / 1.) THF, r.t., 22 h; 2.) CH2Cl2, r.t., 24 h
5: 97 percent / Et3N / DMAP / CH2Cl2 / 88 h / Ambient temperature
6: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
7: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
8: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
9: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 10 steps
1: 85 percent / diisopropylamine, 4-(dimethylamino)pyridine (DMAP) / diethyl ether / 24 h / Ambient temperature
2: 85 percent / 1.) O3, 2.) triphenylphosphine / CH2Cl2 / 1.) -78 deg C, 5 min, 2.) 3 h
3: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 4 h
4: 99 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 22 h / Ambient temperature
5: Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 24 h / Ambient temperature
6: 91 percent / 4-(dimethylamino)pyridine (DMAP), triethylamine / CH2Cl2 / 72 h / Ambient temperature
7: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
8: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
9: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
10: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<1S-<1α,3α,7β,8β(4Σ*,6R*)8aβ>>-<<8-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-1-naphthalenyl>oxy>triethylsilane
116996-44-2

<1S-<1α,3α,7β,8β(4Σ*,6R*)8aβ>>-<<8-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-1-naphthalenyl>oxy>triethylsilane

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: 1.) Bu4NF ; 2.) t-BuPh2SiCl, Et3N / 2.) DMAP / 1.) THF, r.t., 22 h; 2.) CH2Cl2, r.t., 24 h
2: 97 percent / Et3N / DMAP / CH2Cl2 / 88 h / Ambient temperature
3: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
4: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
5: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
6: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 7 steps
1: 99 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 22 h / Ambient temperature
2: Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 24 h / Ambient temperature
3: 91 percent / 4-(dimethylamino)pyridine (DMAP), triethylamine / CH2Cl2 / 72 h / Ambient temperature
4: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
5: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
6: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
7: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<1S-<1α(R*),3α,7β,8β(4S*,6R*),8aβ>>-8-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-1-naphthalenyl 2-methylbutanoate
116996-46-4

<1S-<1α(R*),3α,7β,8β(4S*,6R*),8aβ>>-8-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-1-naphthalenyl 2-methylbutanoate

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
2: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
3: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
4: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 4 steps
1: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
2: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
3: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
4: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<4S-<4α,5α(4S*,6R*),6β(1R*,3S*)>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-4-methyl-6-<3-methyl-1-<(triethylsilyl)oxy>-4-pentenyl>-2-cyclohexen-1-one
117020-89-0

<4S-<4α,5α(4S*,6R*),6β(1R*,3S*)>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-4-methyl-6-<3-methyl-1-<(triethylsilyl)oxy>-4-pentenyl>-2-cyclohexen-1-one

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1: 1.) O3; 2.) Ph3P / 1.) CH2Cl2, -78 deg C; 2.) -78 deg C -> r.t., 3 h
2: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 4 h
3: 1.) Bu4NF ; 2.) t-BuPh2SiCl, Et3N / 2.) DMAP / 1.) THF, r.t., 22 h; 2.) CH2Cl2, r.t., 24 h
4: 97 percent / Et3N / DMAP / CH2Cl2 / 88 h / Ambient temperature
5: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
6: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
7: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
8: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 9 steps
1: 85 percent / 1.) O3, 2.) triphenylphosphine / CH2Cl2 / 1.) -78 deg C, 5 min, 2.) 3 h
2: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 4 h
3: 99 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 22 h / Ambient temperature
4: Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 24 h / Ambient temperature
5: 91 percent / 4-(dimethylamino)pyridine (DMAP), triethylamine / CH2Cl2 / 72 h / Ambient temperature
6: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
7: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
8: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
9: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<1S-<1α(αS,γR*),5β,6β(4Σ*,6R*)>>-6-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-α,5-dimethyl-2-oxo-γ-<(triethylsilyl)oxy>-3-cyclohexene-1-butanal
116996-43-1

<1S-<1α(αS,γR*),5β,6β(4Σ*,6R*)>>-6-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-α,5-dimethyl-2-oxo-γ-<(triethylsilyl)oxy>-3-cyclohexene-1-butanal

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 4 h
2: 1.) Bu4NF ; 2.) t-BuPh2SiCl, Et3N / 2.) DMAP / 1.) THF, r.t., 22 h; 2.) CH2Cl2, r.t., 24 h
3: 97 percent / Et3N / DMAP / CH2Cl2 / 88 h / Ambient temperature
4: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
5: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
6: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
7: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 8 steps
1: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 4 h
2: 99 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 22 h / Ambient temperature
3: Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 24 h / Ambient temperature
4: 91 percent / 4-(dimethylamino)pyridine (DMAP), triethylamine / CH2Cl2 / 72 h / Ambient temperature
5: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
6: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
7: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
8: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
<4R-<4α(4R*,5R*),6α>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-4-methyl-2-cyclohexen-1-one
116996-32-8

<4R-<4α(4R*,5R*),6α>>-5-<2-<6-<2-<<(1,1-dimethylethyl)diphenylsilyl>oxy>ethyl>-2,2-dimethyl-1,3-dioxan-4-yl>ethyl>-4-methyl-2-cyclohexen-1-one

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1: 1.) LDA / 1.)Et2O, -78 deg C, 45 min; 2.) -78 deg C, 10 min
2: 85 percent / i-Pr2NH / DMAP / diethyl ether / 24 h / Ambient temperature
3: 1.) O3; 2.) Ph3P / 1.) CH2Cl2, -78 deg C; 2.) -78 deg C -> r.t., 3 h
4: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / r.t., 5 h; reflux, 4 h
5: 1.) Bu4NF ; 2.) t-BuPh2SiCl, Et3N / 2.) DMAP / 1.) THF, r.t., 22 h; 2.) CH2Cl2, r.t., 24 h
6: 97 percent / Et3N / DMAP / CH2Cl2 / 88 h / Ambient temperature
7: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
8: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
9: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
10: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
Multi-step reaction with 11 steps
1: 1.) lithium diisopropylamide (LDA) / 1.) ether, -78 deg C, 45 min, 2.) -78 deg C, 10 min
2: 85 percent / diisopropylamine, 4-(dimethylamino)pyridine (DMAP) / diethyl ether / 24 h / Ambient temperature
3: 85 percent / 1.) O3, 2.) triphenylphosphine / CH2Cl2 / 1.) -78 deg C, 5 min, 2.) 3 h
4: 86 percent / C8K, TiCl3 / 1,2-dimethoxy-ethane / 1.) RT, 5 h, 2.) reflux, 4 h
5: 99 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 22 h / Ambient temperature
6: Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 24 h / Ambient temperature
7: 91 percent / 4-(dimethylamino)pyridine (DMAP), triethylamine / CH2Cl2 / 72 h / Ambient temperature
8: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
9: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
10: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
11: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
(S)-2-methylbutyric anhydride
84131-91-9

(S)-2-methylbutyric anhydride

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: 97 percent / Et3N / DMAP / CH2Cl2 / 88 h / Ambient temperature
2: 95 percent / Bu4NF / tetrahydrofuran / 3 h / Ambient temperature
3: 1.) (COCl)2; 2.) Et3N / 1.) DMSO, CH2Cl2, -78 deg C, 20 min; 2.) -78 deg C, 10 min, -78 deg C -> r.t., 20 min
4: 97 percent / 1.3N HCl / tetrahydrofuran / 4 h / Ambient temperature
5: 77 percent / Ag2CO3/Celite, PhMe / toluene / 1 h / 90 °C
View Scheme
(S)-2-methylbutanoyl chloride
27763-54-8

(S)-2-methylbutanoyl chloride

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 4-(dimethylamino)pyridine (DMAP), pyridine / 1.) 0 deg C, 1 h, 2.) RT, 18 h
2: acetic acid, Bu4NF*3H2O / tetrahydrofuran / 18 h / Ambient temperature
View Scheme
(4R,6R)-6-[2-((1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl)ethyl]-4-[(tert-butyldimethylsilyl)oxy]-3,4,5,6-tetrahydro-2H-pyran-2-one
79902-31-1

(4R,6R)-6-[2-((1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthyl)ethyl]-4-[(tert-butyldimethylsilyl)oxy]-3,4,5,6-tetrahydro-2H-pyran-2-one

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 4-(dimethylamino)pyridine (DMAP), pyridine / 1.) 0 deg C, 1 h, 2.) RT, 18 h
2: acetic acid, Bu4NF*3H2O / tetrahydrofuran / 18 h / Ambient temperature
View Scheme
(1S,3R,7S,8S,8aR)-8-{2-[(4R,6S)-6-(2-Hydroxy-ethyl)-2,2-dimethyl-[1,3]dioxan-4-yl]-ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-ol
125975-03-3

(1S,3R,7S,8S,8aR)-8-{2-[(4R,6S)-6-(2-Hydroxy-ethyl)-2,2-dimethyl-[1,3]dioxan-4-yl]-ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-ol

lovastatin
75330-75-5

lovastatin

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: Et3N, 4-(dimethylamino)pyridine (DMAP) / CH2Cl2 / 24 h / Ambient temperature
2: 91 percent / 4-(dimethylamino)pyridine (DMAP), triethylamine / CH2Cl2 / 72 h / Ambient temperature
3: 95 percent / 1.1 M Bu4N(1+)*F(1-) / tetrahydrofuran / 3 h / Ambient temperature
4: 97 percent / (COCl)2, DMSO / CH2Cl2 / 0.33 h / -78 °C
5: 97 percent / 10percent aq. HCl / tetrahydrofuran / 4 h / Ambient temperature
6: 77 percent / Ag2CO3/Celite / toluene / 1 h / 85 - 95 °C
View Scheme
lovastatin
75330-75-5

lovastatin

α,β-dehydrolovastatin
109273-98-5

α,β-dehydrolovastatin

Conditions
ConditionsYield
With methanesulfonyl chloride; triethylamine In dichloromethane at 20℃; for 1h;100%
With dmap; methanesulfonyl chloride In acetonitrile at 20℃;90%
With Burgess Reagent In benzene at 60℃; for 1.5h;61%
With methanesulfonyl chloride; triethylamine In dichloromethane at 20℃; for 1h;460 mg
lovastatin
75330-75-5

lovastatin

N-butylamine
109-73-9

N-butylamine

N-butyl-7-<1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-<<2(S)-methylbutanoyl>oxy>-1(S)-naphthyl>-3(R),5(R)-dihydroxyheptanoic acid amide
134970-29-9

N-butyl-7-<1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-<<2(S)-methylbutanoyl>oxy>-1(S)-naphthyl>-3(R),5(R)-dihydroxyheptanoic acid amide

Conditions
ConditionsYield
at 80℃; for 1h;100%
Heating / reflux;
Reflux;
at 70℃; for 3h; Inert atmosphere;
lovastatin
75330-75-5

lovastatin

Cyclopropylamine
765-30-0

Cyclopropylamine

N-cyclopropyl-7-[1,2,6,7,8,8a(R)-hexahydro-2(s),6(R)-dimethyl-8(s)-[[2(S)-methylbutanoyl]oxy]-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid amide

N-cyclopropyl-7-[1,2,6,7,8,8a(R)-hexahydro-2(s),6(R)-dimethyl-8(s)-[[2(S)-methylbutanoyl]oxy]-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid amide

Conditions
ConditionsYield
at 40 - 42℃; for 8h; Inert atmosphere;100%
lovastatin
75330-75-5

lovastatin

monacolin J hydroxy acid
132748-10-8

monacolin J hydroxy acid

Conditions
ConditionsYield
With potassium hydroxide In methanol at 20℃; Reflux;98%
Stage #1: lovastatin; potassium hydroxide In ethanol; water at 20℃; for 12.5 - 17h; Heating / reflux;
Stage #2: With hydrogenchloride; water In diethyl ether at 5 - 10℃; for 1h; pH=5;
93%
Stage #1: lovastatin With potassium hydroxide In water; isopropyl alcohol at 80℃; for 7h;
Stage #2: With hydrogenchloride In water at 12 - 17℃; for 2h; pH=3 - 4; Cooling with ice;
90%
lovastatin
75330-75-5

lovastatin

triethylamine
121-44-8

triethylamine

(3R,5S)-7-[(1S,2S,6R,8S,8aR)-2,6-Dimethyl-8-((S)-2-methyl-butyryloxy)-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl]-3,5-dihydroxy-heptanoic acid; compound with triethyl-amine

(3R,5S)-7-[(1S,2S,6R,8S,8aR)-2,6-Dimethyl-8-((S)-2-methyl-butyryloxy)-1,2,6,7,8,8a-hexahydro-naphthalen-1-yl]-3,5-dihydroxy-heptanoic acid; compound with triethyl-amine

Conditions
ConditionsYield
Stage #1: lovastatin With sodium hydroxide In methanol; water at 20℃; for 2h;
Stage #2: triethylamine In ethyl acetate at 20℃; for 4h;
98%
lovastatin
75330-75-5

lovastatin

(1S,3R,7S,8S,8aR)-8-((3R,5R)-3,5-dihydroxy-7-(hydroxyamino)-7-oxoheptyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (S)-2-methylbutanoate

(1S,3R,7S,8S,8aR)-8-((3R,5R)-3,5-dihydroxy-7-(hydroxyamino)-7-oxoheptyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (S)-2-methylbutanoate

Conditions
ConditionsYield
With hydroxylamine In tetrahydrofuran; water for 72h;98%
With hydroxylamine In tetrahydrofuran; water at 20℃; for 1h;92%
lovastatin
75330-75-5

lovastatin

7-[1',2',6',7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'(S)-naphthyl]-3(R),5 (R)-dihydroxy heptanoic acid

7-[1',2',6',7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'(S)-naphthyl]-3(R),5 (R)-dihydroxy heptanoic acid

Conditions
ConditionsYield
With potassium tert-butylate In tetrahydrofuran; water at -30 - 20℃; for 5h;94%
pivaloyl chloride
3282-30-2

pivaloyl chloride

lovastatin
75330-75-5

lovastatin

(2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl 2,2-dimethylpropanoate
479482-41-2

(2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl 2,2-dimethylpropanoate

Conditions
ConditionsYield
With pyridine In toluene at 20℃;92%
With pyridine In toluene at 20℃; for 24h; Inert atmosphere;77%
benzoyl chloride
98-88-4

benzoyl chloride

lovastatin
75330-75-5

lovastatin

(2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl benzoate
81189-93-7

(2R,4R)-2-[2-((1S,2S,6R,8S,8aR)-1,2,3,7,8,8a-hexahydro-2,6-dimethyl-8-{[(S)-2-methylbutanoyl]oxy}naphthalen-1-yl)ethyl]-3,4,5,6-tetrahydro-6-oxo-2H-pyran-4-yl benzoate

Conditions
ConditionsYield
With pyridine In toluene at 20℃; for 18h;91%
With pyridine In toluene at 20℃; for 24h; Inert atmosphere;85%
lovastatin
75330-75-5

lovastatin

6(R)-<2-<1,2,3,5,6,7,8,8a(R)-Octahydro-2(S),6(R)-dimethyl-8(R)-<<2(S)-methylbutyryl>oxy>-1(S)-naphthyl>ethyl>-3,4,5,6-tetrahydro-4(R)-hydroxy-2H-pyran-2-one
79691-09-1

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

Conditions
ConditionsYield
With (η4-1,5-cyclooctadiene)(pyridine)(tricyclohexylphosphine)iridium(I) hexafluorophosphate; hydrogen In dichloromethane at 20℃; under 760 Torr; for 1.5h;90%
Multi-step reaction with 2 steps
1: 1.48 g / imidazole / dimethylformamide / 5 h / 35 °C
2: 50 mg / triethylsilane, trifluoroacetic acid / CH2Cl2 / 24 h / Ambient temperature
View Scheme
lovastatin
75330-75-5

lovastatin

7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-hydroxy-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid
761354-04-5

7-[1,2,6,7,8,8a(R)-hexahydro-2(S),6(R)-dimethyl-8(S)-hydroxy-1(S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid

Conditions
ConditionsYield
Stage #1: lovastatin With potassium hydroxide; ethanol; water In isopropyl alcohol at 20℃; for 6.5h; Heating / reflux;
Stage #2: With hydrogenchloride In water; isopropyl alcohol for 1h; pH=<= 3;
90%
lovastatin
75330-75-5

lovastatin

A

(4R,6R)-4-hydroxy-6-(2-((1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)ethyl)tetrahydro-2H-pyran-2-one
151006-15-4, 79952-42-4

(4R,6R)-4-hydroxy-6-(2-((1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)ethyl)tetrahydro-2H-pyran-2-one

B

monacolin J hydroxy acid
132748-10-8

monacolin J hydroxy acid

Conditions
ConditionsYield
Stage #1: lovastatin With ammonia; water; enzyme SEQ ID NO:4 (encoded by SEQ ID NO:3) at 40℃; for 18.75 - 27h; pH=9.5; Enzymatic reaction;
Stage #2: In water pH=2.5; Product distribution / selectivity; Acidic aqueous solution;
A n/a
B 89.4%
Stage #1: lovastatin With methanol; sodium hydroxide; water at 20℃;
Stage #2: With hydrogenchloride In methanol; water pH=7 - 8;
Stage #3: With hydrogenchloride; methanol; methanesulfonic acid; ammonia; water; lovastatin esterase SEQ ID NO:4 (encoded by SEQ ID NO:3) Product distribution / selectivity; more than 3 stages;
With water; potassium hydroxide In methanol for 21h; Reflux;
lovastatin
75330-75-5

lovastatin

(4R,6R)-4-hydroxy-6-(2-((1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)ethyl)tetrahydro-2H-pyran-2-one
151006-15-4, 79952-42-4

(4R,6R)-4-hydroxy-6-(2-((1S,2S,6R,8S,8aR)-8-hydroxy-2,6-dimethyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)ethyl)tetrahydro-2H-pyran-2-one

Conditions
ConditionsYield
Stage #1: lovastatin With water; lithium hydroxide at 100℃;
Stage #2: With hydrogenchloride In water pH=< 2;
Stage #3: With calcium hydride In toluene at 110℃; for 1h;
89%
With lithium hydroxide In tetrahydrofuran; methanol at 66℃; for 2h; Inert atmosphere;73%
With lithium hydroxide for 24h; Heating;
lovastatin
75330-75-5

lovastatin

tert-butylamine
75-64-9

tert-butylamine

lovastatin tert-butylamine salt

lovastatin tert-butylamine salt

Conditions
ConditionsYield
With water at 50 - 55℃; for 3.5h;88%
lovastatin
75330-75-5

lovastatin

(1S,3R,7S,8S,8aR)-3,7-dimethyl-8-((3R,5S)-3,5,7-trihydroxyheptyl)-1,2,3,7,8,8ahexahydronaphthalen-1-yl 2-methylbutanoate
221192-13-8

(1S,3R,7S,8S,8aR)-3,7-dimethyl-8-((3R,5S)-3,5,7-trihydroxyheptyl)-1,2,3,7,8,8ahexahydronaphthalen-1-yl 2-methylbutanoate

Conditions
ConditionsYield
With samarium diiodide; water; triethylamine In tetrahydrofuran at 20℃; for 1h; Inert atmosphere;87%
lovastatin
75330-75-5

lovastatin

2-naphthaloyl chloride
2243-83-6

2-naphthaloyl chloride

(S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-(2-naphthoyloxy)-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

(S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-(2-naphthoyloxy)-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

Conditions
ConditionsYield
With pyridine In toluene at 20℃; for 24h; Inert atmosphere;86%
lovastatin
75330-75-5

lovastatin

<1S-<1α(3R*,5S*),2α,6β,8β,8aα>>-7-(1,2,6,7,8,8a-Hexahydro-8-hydroxy-2,6-dimethyl-1-naphthalenyl)-1,3,5-heptanetriol
148969-22-6

<1S-<1α(3R*,5S*),2α,6β,8β,8aα>>-7-(1,2,6,7,8,8a-Hexahydro-8-hydroxy-2,6-dimethyl-1-naphthalenyl)-1,3,5-heptanetriol

Conditions
ConditionsYield
With lithium aluminium tetrahydride84%
With lithium aluminium tetrahydride In tetrahydrofuran for 5h;84%
With lithium aluminium tetrahydride In diethyl ether for 3h;80%
acetic anhydride
108-24-7

acetic anhydride

lovastatin
75330-75-5

lovastatin

(S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-acetoxy-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester
81189-92-6

(S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-acetoxy-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

Conditions
ConditionsYield
With pyridine at 20℃; for 2.5h; Inert atmosphere;84%
lovastatin
75330-75-5

lovastatin

(1S,3R,7S,8S,8aR)-8-((3R,5R)-7-amino-3,5-dihydroxy-7-oxoheptyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (S)-2-methylbutanoate
118159-61-8

(1S,3R,7S,8S,8aR)-8-((3R,5R)-7-amino-3,5-dihydroxy-7-oxoheptyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (S)-2-methylbutanoate

Conditions
ConditionsYield
With ammonia In methanol at 20℃; for 24h;79%
lovastatin
75330-75-5

lovastatin

(1S,3R,7S,8S,8aR)-7,7-dideuterio-3,7-dimethyl-8-((3R,5S)-3,5,7-trihydroxyheptyl)-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2-methylbutanoate

(1S,3R,7S,8S,8aR)-7,7-dideuterio-3,7-dimethyl-8-((3R,5S)-3,5,7-trihydroxyheptyl)-1,2,3,7,8,8a-hexahydronaphthalen-1-yl 2-methylbutanoate

Conditions
ConditionsYield
With samarium diiodide; water-d2 In tetrahydrofuran at 23℃; for 2h; Inert atmosphere; chemoselective reaction;74%
succinic acid anhydride
108-30-5

succinic acid anhydride

lovastatin
75330-75-5

lovastatin

lovastatin succinate monoester

lovastatin succinate monoester

Conditions
ConditionsYield
With pyridine at 50℃; for 48h;72%
lovastatin
75330-75-5

lovastatin

chloroacetyl chloride
79-04-9

chloroacetyl chloride

C26H37ClO6

C26H37ClO6

Conditions
ConditionsYield
With pyridine In toluene at 0 - 20℃; for 18h;70%
4-(trifluoromethoxy)benzoyl chloride
36823-88-8

4-(trifluoromethoxy)benzoyl chloride

lovastatin
75330-75-5

lovastatin

(S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-(4-trifluoromethoxybenzoyloxy)-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

(S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-(4-trifluoromethoxybenzoyloxy)-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

Conditions
ConditionsYield
With pyridine In toluene at 20℃; for 24h; Inert atmosphere;64%
4-chloro-benzoyl chloride
122-01-0

4-chloro-benzoyl chloride

lovastatin
75330-75-5

lovastatin

(S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-(4-chlorobenzoyloxy)-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

(S)-2-methyl-butyric acid (3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-(4-chlorobenzoyloxy)-6-oxo-tetrahydro-pyran-2yl]-ethyl}-3,7-dimetyl-1,2,3,7,8,8a-hexahydro-naphthalen-1-yl ester

Conditions
ConditionsYield
With pyridine In toluene at 20℃; for 24h; Inert atmosphere;64%
4-(methylsulfinyl)benzoic acid
33963-58-5

4-(methylsulfinyl)benzoic acid

lovastatin
75330-75-5

lovastatin

(2R,4R)-2-(2-((1S,2S,6R,8S,8aR)-2,6-dimethyl-8-(((S)-2-methylbutanoyl)oxy)-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)ethyl)-6-oxotetrahydro-2H-pyran-4-yl 4-(methylsulfinyl)benzoate

(2R,4R)-2-(2-((1S,2S,6R,8S,8aR)-2,6-dimethyl-8-(((S)-2-methylbutanoyl)oxy)-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)ethyl)-6-oxotetrahydro-2H-pyran-4-yl 4-(methylsulfinyl)benzoate

Conditions
ConditionsYield
Stage #1: 4-(methylsulfinyl)benzoic acid; lovastatin With dicyclohexyl-carbodiimide In dichloromethane for 0.166667h; Inert atmosphere; Cooling with ice;
Stage #2: With dmap In dichloromethane at 20℃; for 16h; Inert atmosphere; Cooling with ice;
63%

75330-75-5Upstream product

75330-75-5Relevant articles and documents

Stereocontrolled functionalization of the diene system of compactin

Senanayake, Chris H.,Bill, Timothy J.,DiMichele, Lisa M.,Chen, Cheng Y.,Larsen, Robert D.,Verhoeven, Thomas R.,Reider, Paul J.

, p. 6021 - 6024 (1993)

A facile regio- and stereo selective γ-functionlization of the 1,3-diene system of compactin via the key dienone 3 is described.

Drug or Supplement Combination with Conjugated Linoleic Acid for Fat Loss in Mammals

-

, (2010/06/22)

Food, feed or drug combinations with conjugated linoleic acid are described that cause enhanced fat loss in mammals more efficiently than any of the individual components of the combination. Food, feed, or drugs that activate AMP activated protein kinase, agonists of nuclear receptors that bind RXR in adipocytes, or statin inhibitors were found to be more effective for fat loss when combined with conjugated linoleic acid.

AN IMPROVED METHOD FOR MANUFACTURE OF 4-HYDROXY PYRAN-2-ONE DERIVATIVES

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Page/Page column 27; 28, (2008/06/13)

A process for preparation of 4-hydroxy-pyran-2-one derivative of formula (I), wherein R is (a), and wherein R1 and R2 are methyl and R3 is hydrogen or methyl, comprising the steps of, heating a compound of formula (II), wherein R is as defined before, and R4 is hydrogen, NH4+ or an alkali metal, in a solvent mixture consisting of an aromatic hydrocarbon and a ketone in an inert atmosphere at a temperature of between 60°C to 92°C in the absence or presence of orthophosphoric acid or its alkali dihydrogen salts or alkali hydrogen salts of a dibasic acid, followed by optional neutralization of the reaction mixture with an organic base and obtaining compound of formula (I) in high purity and substantially free of impurities through a step of isolation and crystallization. The process leads to formation of derivatives of formula (I) in high purity with dimmer impurity (III) less than 0.1% and anhydro impurity (IV) below 0.15%.

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