674-26-0

Basic information

• Product Name: DL-Mevalonolactone
• Synonyms: DL-MEVALONOLACTONE;DL-MEVALOLACTONE;DL-MEVALONIC ACID LACTONE;DL-BETA-HYDROXY-BETA-METHYL-DELTA-VALERO-LACTONE;DL-BETA-HYDROXY-BETA-METHYL-GAMMA-VALEROLACTONE;DL-BETA-HYDROXY-BETA-METHYL-G-VALEROLACTONE;DL-3-HYDROXY-3-METHYL DELTA-VALEROLACTONE;BETA-HYDROXY-BETA-METHYL-DELTA-VALEROLACTONE
• CAS NO: 674-26-0
• Molecular Formula: C₆H₁₀O₃
• Molecular Weight: 130.14
• EINECS: 211-615-0
• Product Categories: Heterocycles;Metabolites & Impurities;Heterocycles, Metabolites & Impurities
• Mol File: 674-26-0.mol
• Article Data: 24

Chemical Properties

• Melting Point: 28 °C(lit.)
• Boiling Point: 145-150 °C5 mm Hg(lit.)
• Flash Point: >230 °F
• Appearance: Moist pale yellow to off white solid
• Density: 1.1066 (rough estimate)
• Vapor Pressure: 0.000662mmHg at 25°C
• Refractive Index: n20/D 1.473(lit.)
• Storage Temp.: 2-8°C
• Solubility: Chloroform (Sparingly), DMSO (Slightly), Ethyl Acetate, Methanol (Slightly)
• PKA: 13.57±0.20(Predicted)
• Stability: Hygroscopic
• Merck: 14,6163
• BRN: 80960
• CAS DataBase Reference: DL-Mevalonolactone(CAS DataBase Reference)
• NIST Chemistry Reference: DL-Mevalonolactone(674-26-0)
• EPA Substance Registry System: DL-Mevalonolactone(674-26-0)

Safety Data

• WGK Germany: 3
• F: 3-10
• Hazardous Substances Data: 674-26-0(Hazardous Substances Data)

Usage

Description

DL-Mevalonolactone is the δ-lactone form of mevalonic acid, a precursor in the mevalonate pathway. It induces depolarization and swelling, decreases NADPH content and aconitase (ACO) activity, and increases malondialdehyde (MDA) production in calcium-loaded rat brain mitochondria. DL-Mevalonolactone reverses decreases in glucose uptake induced by simvastatin (Item Nos. 10010344 | 10010345) in L6 myotubes. Tissue levels and urinary excretion of DL-mevalonolactone are increased in patients with mevalonic aciduria, a disorder characterized by a deficiency in mevalonic kinase activity.

Chemical Properties

Pale Yellow Oil

Uses

Different sources of media describe the Uses of 674-26-0 differently. You can refer to the following data:
1. A metabolite from endophytes of the medicinal plant Erythrina crista-galli.
2. HMG CoA substrate
3. (±)-Mevalonolactone is used to:study the effect of statin on the prenylation of Ras and Rho GTPasesanalyse the isoprenoid biosynthesis pathways in Listeria monocytogenesstudy the the effects of statins on proliferation and migration of HUVECs (HGF-induced human umbilical vein endothelial cells)

Synthesis Reference(s)

Journal of the American Chemical Society, 104, p. 5486, 1982 DOI: 10.1021/ja00384a040Synthesis, p. 719, 1974 DOI: 10.1055/s-1974-23416

General Description

Alkaline hydrolysis of mevalonolactone gives mevalonate. Mevalonate is a precursor of farnesyl and geranylgeranyl pyrophosphates. These pyrophosphates are required for protein prenylation.

Purification Methods

Purify the lactone via the dibenzyl-ethylenediammonium salt (m 124-125o) [Hofmann et al. J Am Chem Soc 79 2316 1957], or by chromatography on paper or on a Dowex-1 (formate) column. [Bloch et al. J Biol Chem 234 2595 1959.] Store it as the N,N'-dibenzylethylenediamine (DBED) salt, or as the lactone in a sealed container at 0o. [Beilstein 18/1 V 19.]

InChI:InChI=1/C6H10O3/c1-6(8)2-3-9-5(7)4-6/h8H,2-4H2,1H3

Synthetic route

3-methyl-1,3,5-pentanetriol (7564-64-9) → mevalonolactone (674-26-0)

Conditions	Yield
With pyridinium chlorochromate In dichloromethane for 4h; Ambient temperature;	92%
With aluminum oxide; sodium bromite In dichloromethane for 1.5h; Ambient temperature;	85%
With peracetic acid; sodium bromide In ethyl acetate at 39.9℃; for 2h;	83%
With 1-methyl-1H-imidazole; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; tetrakis(acetonitrile)copper(I) trifluoromethanesulfonate In acetonitrile at 22℃; for 6h;	83%

4-(4-Methoxy-benzyloxymethoxy)-4-methyl-tetrahydro-pyran-2-one (118617-84-8) → mevalonolactone (674-26-0)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane; water for 10h; Ambient temperature; cleavage of (p-methoxybenzyloxy)methyl protecting group;	89%

2,3,5,6-tetrahydro-4-methylpyran-2,4-diol (99720-12-4) → mevalonolactone (674-26-0)

Conditions	Yield
With sodium acetate; pyridinium chlorochromate In dichloromethane for 6h; Ambient temperature;	82%

D,L-mevalonic acid (150-97-0, 690-72-2, 17817-88-8, 32451-23-3) → mevalonolactone (674-26-0)

Conditions	Yield
With sulfuric acid for 15h; Reflux;	82%
Multi-step reaction with 2 steps 1: tetrabutylammomium bromide / tetrahydrofuran / 4 h / 50 °C / Inert atmosphere 2: pyridine / dichloromethane / 0.5 h / 0 °C / Inert atmosphere View Scheme

trimethylsilyl acetate (2754-27-0) + 4-((trimethylsilyl)oxy)-3-butanone (81852-67-7) → mevalonolactone (674-26-0)

Conditions	Yield
With lithium diisopropyl amide 1.) THF, -78 deg C, 2 h, 2.) -78 deg C, 2 h;	81%

ethyl 3-hydroxy-3-methyl-5-<(2-tetrahydropyranyl)-oxy>pentanoate (80514-97-2) → mevalonolactone (674-26-0)

Conditions	Yield
With acetyl chloride In ethanol for 10h; Ambient temperature;	80%
With acetyl chloride In ethanol Ambient temperature; overnight;	22 g

3-hydroxy-3-methylglutaric anhydride (34695-32-4) → mevalonolactone (674-26-0)

Conditions	Yield
With sodium tetrahydroborate In isopropyl alcohol	75.6%
With sodium tetrahydroborate In isopropyl alcohol Ambient temperature;	300 mg
With sodium tetrahydroborate In isopropyl alcohol for 24h; Ambient temperature;
Multi-step reaction with 2 steps 1: 1.) CH2Cl2, -20 deg C, 7 days 2: 1.) LiCl, NaBH4; 2.) 10percent KOH / 1.) EtOH, 50 deg C, 24 h; 2.) MeOH, 60 deg C, 4h View Scheme

bis(trichloromethyl) carbonate (32315-10-9) + benzyl 3,5-dihydroxy-3-methylpentanoate (1452161-92-0) → benzyl 2-(4-methyl-2-oxo-1,3-dioxan-4-yl)acetate (1452161-93-1) + mevalonolactone (674-26-0)

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 0.5h; Inert atmosphere;	A 64% B 12%

5-chloro-3-hydroxy-3-methylvaleric acid (128811-87-0) → mevalonolactone (674-26-0)

Conditions	Yield
With potassium carbonate; Katamin AB In acetone at 40 - 45℃; for 3h;	60%

5-[(4-nitrophenyl)methylcarbamoyloxy]-3-hydroxy-3-methylpentanoic acid (246237-03-6) → mevalonolactone (674-26-0)

Conditions	Yield
With sodium hydroxide In methanol at 20℃; Cyclization; Deprotection;	17%

Ketene (463-51-4) + 1-acetoxybutan-3-one (10150-87-5) → mevalonolactone (674-26-0)

Conditions	Yield
With diethyl ether; boron trifluoride behandeln des Reaktionsprodukts mit methanol. Kalilauge und anschliessend mit Chlorwasserstoff enthaltendem Methanol;

1,1-diallylethanol (25201-40-5) + acetic acid (64-19-7) → mevalonolactone (674-26-0)

Conditions	Yield
With ozone Behandeln des Reaktionsgemisches mit Natriumboranat in Aethanol und Erhitzen des Reaktionsprodukts mit Aluminiumisopropylat in Xylol;

(R/S)-3-methyl-5-hexene-1,3-diol (114580-75-5) + acetic acid (64-19-7) → mevalonolactone (674-26-0)

Conditions	Yield
With ozone anschliessend mit wss.Wasserstoffperoxid;

3-acetoxy-3-methylpentane-1,5-dioic acid anhydride (87894-65-3) → 4-methyl-5,6-dihydro-2H-pyran-2-one (2381-87-5) + 5-O-acetylmevalonic acid (78501-60-7) + mevalonolactone (674-26-0)

Conditions	Yield
With sodium tetrahydroborate In isopropyl alcohol for 24h; Ambient temperature; Title compound not separated from byproducts;

t-butyldimethylsiyl triflate (69739-34-0) → mevalonolactone (674-26-0)

Conditions	Yield
Multistep reaction;

butyl <2-13C,2H3>acetate (120388-51-4) → mevalonolactone (674-26-0)

Conditions	Yield
	0.82 g

β-hydroxy-β-methylglutarylhydroxyabscisic acid → (+/-)-Phaseic acid (24394-14-7, 127516-44-3, 128821-87-4) + mevalonolactone (674-26-0)

Conditions	Yield
With borane In tetrahydrofuran 1.) -18 deg C, 30 min, 2.) room temp.;	A 1.0 mg B 0.6 mg

3-Hydroxy-3-methyl-4-(2'-morpholin-4-yl-[1,1']binaphthalenyl-2-ylcarbamoyl)-butyric acid methyl ester (94726-38-2, 106402-01-1) → mevalonolactone (674-26-0)

Conditions	Yield
With potassium hydroxide; sodium tetrahydroborate; lithium chloride 1.) EtOH, 50 deg C, 24 h; 2.) MeOH, 60 deg C, 4h; Yield given. Multistep reaction;

(+-)-3,5-dihydroxy-3-methyl-valeric acid ethyl ester → mevalonolactone (674-26-0)

Conditions	Yield
With barium dihydroxide; water at 120℃; Behandeln des erhaltenen Barium-Salzes mit wss.Schwefelsaeure und Erhitzen des Reaktionsprodukts;

(+-)-5-acetoxy-3-hydroxy-3-methyl-valeric acid ethyl ester → mevalonolactone (674-26-0)

Conditions	Yield
With sodium hydroxide; ethanol Erwaermen der erhaltenen, ueber das N,N'-Dibenzyl-aethylendiamin-Salz gereinigten (+-)-3,5-Dihydroxy-3-methyl-valeriansaeure unter 0.3 Torr;

(+-)-5-acetoxy-3-hydroxy-3-methyl-valeric acid methyl ester → mevalonolactone (674-26-0)

Conditions	Yield
With methanol; potassium hydroxide anschliessend mit Chlorwasserstoff enthaltendem Methanol;

(+-)-barium-<3-hydroxy-5,5-dimethoxy-3-methyl valerate > → mevalonolactone (674-26-0)

Conditions	Yield
With hydrogenchloride Behandeln der mit wss.Natronlauge neutralisierten Reaktionsloesung mit Kaliumboranat und anschliessend mit wss.Salzsaeure;

acetic acid (64-19-7) + (+-)-5-acetoxy-1,1-dimethoxy-3-methyl-pentan-3-ol → mevalonolactone (674-26-0)

Conditions	Yield
With sulfuric acid; dihydrogen peroxide

(R/S)-3-methyl-5-hexene-1,3-diol (114580-75-5) → mevalonolactone (674-26-0)

Conditions

Yield

Multi-step reaction with 5 steps 1: 285 mg / DMAP; NEt3 / tetrahydrofuran; toluene / 90 h / 20 °C 2: 4-methylmorpholine N-oxide; OsO4 / CH2Cl2; H2O; 2-methyl-propan-2-ol / 0.75 h 3: 409.1 mg / Pb(OAc)4 / CH2Cl2; H2O; 2-methyl-propan-2-ol / 0.17 h 4: 77 percent / KMnO4 / diethyl ether; aq. phosphate buffer; 2-methyl-propan-2-ol / 0.08 h / 20 °C / pH 7.4 5: 17 percent / NaOH / methanol / 20 °C View Scheme

(4-nitrophenyl)methylcarbamic acid 3-hydroxy-3-methyl-5-oxopentyl ester (246236-98-6) → mevalonolactone (674-26-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 77 percent / KMnO4 / diethyl ether; aq. phosphate buffer; 2-methyl-propan-2-ol / 0.08 h / 20 °C / pH 7.4 2: 17 percent / NaOH / methanol / 20 °C View Scheme

methyl-(4-nitro-phenyl)-carbamic acid 3-hydroxy-3-methyl-hex-5-enyl ester (246237-00-3) → mevalonolactone (674-26-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 4-methylmorpholine N-oxide; OsO4 / CH2Cl2; H2O; 2-methyl-propan-2-ol / 0.75 h 2: 409.1 mg / Pb(OAc)4 / CH2Cl2; H2O; 2-methyl-propan-2-ol / 0.17 h 3: 77 percent / KMnO4 / diethyl ether; aq. phosphate buffer; 2-methyl-propan-2-ol / 0.08 h / 20 °C / pH 7.4 4: 17 percent / NaOH / methanol / 20 °C View Scheme

methyl-(4-nitro-phenyl)-carbamic acid 3,5,6-trihydroxy-3-methyl-hexyl ester → mevalonolactone (674-26-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 409.1 mg / Pb(OAc)4 / CH2Cl2; H2O; 2-methyl-propan-2-ol / 0.17 h 2: 77 percent / KMnO4 / diethyl ether; aq. phosphate buffer; 2-methyl-propan-2-ol / 0.08 h / 20 °C / pH 7.4 3: 17 percent / NaOH / methanol / 20 °C View Scheme

1,1-diallylethanol (25201-40-5) → mevalonolactone (674-26-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1.) O3, 2.) H2O2 / 1.) CH2Cl2, CH3COOH, -78 deg C, 2.) CH3COOH 2: (CH3CO)2O / 14 h / Ambient temperature 3: 75.6 percent / NaBH4 / propan-2-ol View Scheme
Multi-step reaction with 3 steps 1: 1.) ozone, acetic acid, 2.) hydrogen peroxide / 1.) methylene dichloride, -78 deg C, 2.) water, reflux, 13 h 2: 673 mg / acetic anhydride / 72 h / 18 °C / further reagents, reaction conditions 3: 300 mg / sodium borohydride / propan-2-ol / Ambient temperature View Scheme

meglutol (503-49-1) → mevalonolactone (674-26-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: (CH3CO)2O / 14 h / Ambient temperature 2: 75.6 percent / NaBH4 / propan-2-ol View Scheme
Multi-step reaction with 2 steps 1: 673 mg / acetic anhydride / 72 h / 18 °C / further reagents, reaction conditions 2: 300 mg / sodium borohydride / propan-2-ol / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: lithium aluminium tetrahydride / tetrahydrofuran / 16 h / 0 - 20 °C 2: tetrakis(acetonitrile)copper(I) trifluoromethanesulfonate; [2,2]bipyridinyl; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; 1-methyl-1H-imidazole / acetonitrile / 6 h / 22 °C View Scheme

3,4-dihydro-2H-pyran (110-87-2) + mevalonolactone (674-26-0) → 4-Methyl-4-(tetrahydro-pyran-2-yloxy)-tetrahydro-pyran-2-one (100689-33-6, 120445-02-5)

Conditions	Yield
triphenylphosphine hydrobromide In dichloromethane for 7h; Ambient temperature;	96%
With lithium hexafluorophosphate In hexane at 0℃; for 4.5h;	49%

mevalonolactone (674-26-0) → 4-methyl-5,6-dihydro-2H-pyran-2-one (2381-87-5)

Conditions	Yield
With toluene-4-sulfonic acid In benzene for 19h; Reflux;	93%
With PPA	89%
With toluene-4-sulfonic acid In benzene for 20h; Reflux; Dean-Stark;	89%

para-methoxybenzyl chloride (88023-78-3) + mevalonolactone (674-26-0) → 4-(4-Methoxy-benzyloxymethoxy)-4-methyl-tetrahydro-pyran-2-one (118617-84-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 30h; Ambient temperature;	84%

benzyl isothiocyanate (3173-56-6) + mevalonolactone (674-26-0) → Benzyl-carbamic acid 4-methyl-2-oxo-tetrahydro-pyran-4-yl ester (123034-94-6)

Conditions	Yield
copper(l) chloride In N,N-dimethyl-formamide Ambient temperature;	80%

mevalonolactone (674-26-0) → meglutol (503-49-1)

Conditions	Yield
With nitric acid; sodium nitrite at 35 - 40℃; for 5h;	76%
With nitric acid at 40℃; for 4h; Cooling with ice;	57%

9-ethyl-9H-carbazol-3-ylamine (132-32-1) + mevalonolactone (674-26-0) → N-(9-ethyl-9H-carbazol-3-yl)-3,5-dihydroxy-3-methylpentanamide (1427185-29-2)

Conditions	Yield
Stage #1: 9-ethyl-9H-carbazol-3-ylamine With trimethylaluminum In toluene at 10 - 35℃; for 0.5h; Stage #2: mevalonolactone In toluene at 0℃; for 4h;	74%

hexan-1-amine (111-26-2) + mevalonolactone (674-26-0) → 1-hexyl-4-methyl-2-piperidin-3-enone (1072454-00-2)

Conditions	Yield
With 1-butyl-3-methylimidazolium Tetrafluoroborate In 1,4-dioxane at 240℃; for 0.583333h; Microwave irradiation;	73%

benzyl bromide (100-39-0) + mevalonolactone (674-26-0) → benzyl 3,5-dihydroxy-3-methylpentanoate (1452161-92-0)

Conditions	Yield
Stage #1: mevalonolactone With water; potassium hydroxide at 20 - 40℃; for 1h; Stage #2: benzyl bromide With hydrogenchloride; tetrabutylammomium bromide In tetrahydrofuran; water at 20 - 50℃; for 4h; pH=7 - 8;	69%

2,3,4,5,6-pentafluorobenzylamine (1548-77-2) + mevalonolactone (674-26-0) → 3,5-Dihydroxy-3-methyl-N-((perfluorophenyl)methyl)pentanamide (1452162-37-6)

Conditions	Yield
In N,N-dimethyl-formamide at 80℃; for 12h; Inert atmosphere;	53%

2,3,4,5,6-pentafluorobenzamide (652-31-3) + mevalonolactone (674-26-0) → 3,5-Dihydroxy-3-methyl-N-((perfluorophenyl)methyl)pentanamide (1452162-37-6)

Conditions	Yield
In N,N-dimethyl-formamide at 20 - 80℃; for 12h; Inert atmosphere;	53%

D-(+)-glucosamine hydrochloride (66-84-2) + mevalonolactone (674-26-0) → N-glucosylmevalonamide

Conditions	Yield
With sodium hydroxide In water at 55℃; for 5h; Heating;	47%

mevalonolactone (674-26-0) → 3,5-dihydroxy-3-methyl-valeraldehyde-(2,4-dinitro-phenylhydrazone) (105338-90-7)

Conditions	Yield
With tetrahydrofuran; lithium aluminium tetrahydride Erwaermen des Reaktionsprodukts mit <2,4-Dinitro-phenyl>-hydrazin und wss.-methanol. HCl;

Benzhydrylamine (91-00-9) + mevalonolactone (674-26-0) → (+/-)-3,5-dihydroxy-3-methyl-valeric acid benzhydrylamide (5973-99-9)

Conditions	Yield
at 110℃; for 1h;

mevalonolactone (674-26-0) + methyl iodide (74-88-4) → 3,5-dihydroxy-3-methylpentanoic acid methyl ester (10371-61-6)

Conditions	Yield
(i) ion-exchange resin + form>, H2O, (ii) Ag2O, (iii) /BRN= 969135/, THF; Multistep reaction;

mevalonolactone (674-26-0) → 3-methyl-1,3,5-pentanetriol (7564-64-9)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran
With lithium aluminium tetrahydride In tetrahydrofuran for 18h; Reflux;	2.1 g

(R)-1-(1-Naphthyl)ethylamine (3886-70-2) + (R)-methoxytrifluoromethylphenylacetyl chloride (20445-33-4, 39637-99-5) + mevalonolactone (674-26-0) → (R)-3,3,3-Trifluoro-2-methoxy-2-phenyl-propionic acid 3-hydroxy-3-methyl-4-((R)-1-naphthalen-1-yl-ethylcarbamoyl)-butyl ester (72165-50-5, 72203-59-9)

Conditions	Yield
With pyridine 1.) 70- 80 deg C, 3 h, 2.) RT; Multistep reaction;

tirucallol (79-63-0) + mevalonolactone (674-26-0) → 4,4-dimethyl-5α-cholesta-8,24-dien-3β-ol (7448-02-4)

Conditions	Yield
With arsenite rat liver extracts, phosphate buffer, pH 7.4, sucrose;

Upstream product

• 25201-40-5 1,1-diallylethanol 
• 64-19-7 acetic acid 
• 114580-75-5 (R/S)-3-methyl-5-hexene-1,3-diol 
• 7564-64-9 3-methyl-1,3,5-pentanetriol 
• 34695-32-4 3-hydroxy-3-methylglutaric anhydride 
• 463-51-4 Ketene 
• 10150-87-5 1-acetoxybutan-3-one 
• 57-50-1 Sucrose 
• 56-81-5 glycerol 
• 127-09-3 sodium acetate 
• 50-99-7 D-glucose 
• 53120-74-4 3,3-dimethylpent-1,5-diol 
• 128811-86-9 4-(β-chloroethyl)-4-methyl-1,3-dioxane 
• 2018-45-3 4-(β-hydroxyethyl)-4-methyl-1,3-dioxane 

Downstream Products

• 39149-97-8 (Z)-3-methylpent-2-ene-1,5-diol 
• 563-80-4 3-methyl-butan-2-one 
• 2381-87-5 4-methyl-5,6-dihydro-2H-pyran-2-one 
• 75-65-0 tert-butyl alcohol 
• 78-79-5 isoprene 
• 763-32-6 2-methyl-1-buten-4-ol 
• 99-87-6 4-methylisopropylbenzene 
• 95-93-2 1,2,4,5-tetramethylbenzene 
• 600-15-7 2-Hydroxybutanoic acid 
• 64-17-5 ethanol 
• 630-19-3 pivalaldehyde 
• 78-94-4 methyl vinyl ketone 
• 563-46-2 2-Methyl-1-butene 
• 115-11-7 isobutene 

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