150-97-0

Basic information

• Product Name: 3,5-dihydroxy-3-methyl-Pentanoic acid
• Synonyms: 3,5-dihydroxy-3-methyl-Pentanoic acid;Mevalonic acid;2,4-Dideoxy-3-C-methylpentonic Acid;3,5-Dihydroxy-3-methylvaleric Acid;D,L-Mevalonic Acid;Hiochic Acid;MK 91;MVS
• CAS NO: 150-97-0
• Molecular Formula: C₆H₁₂O₄
• Molecular Weight: 148.16
• Product Categories: All Aliphatics;Aliphatics;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 150-97-0.mol
• Article Data: 3

Chemical Properties

• Melting Point: 151-152 °C(Solv: benzene (71-43-2))
• Boiling Point: 364.1°Cat760mmHg
• Flash Point: 188.2°C
• Appearance: /
• Density: 1.263g/cm³
• Vapor Pressure: 8.91E-07mmHg at 25°C
• Refractive Index: 1.499
• Storage Temp.: 2-8°C
• PKA: 4.33±0.10(Predicted)
• CAS DataBase Reference: 3,5-dihydroxy-3-methyl-Pentanoic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-dihydroxy-3-methyl-Pentanoic acid(150-97-0)
• EPA Substance Registry System: 3,5-dihydroxy-3-methyl-Pentanoic acid(150-97-0)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 150-97-0(Hazardous Substances Data)

Usage

Uses

Precursor in the biosynthesis of cholesterol. Occurs in equilibrium with the d-lactone

Definition

Anorganic acid, it is an intermediate in the biosyn-thesis of squalene, cholesterol, and coenzyme q inplants and animals.

Biosynthesis

Mevalonic acid is the primary precursor of an the terpenoids and steroids biosynthesised by plants. It is derived from acetyl CoA through the intermediate formation of acetoacetyl CoA and 3-hydroxy-3-methylglutaryl CoA (HMG CoA), these reactions being catalysed by acetyl CoA acetyltransferase and HMG CoA synthase, respectively. Reduction of HMG CoA, catalysed by HMG CoA reductase, gives mevalonic acid. Before the pathway can continue, mevalonic acid must be catalytically phosphorylated by ATP and mevalonic acid kinase. Mevalonic acid kinase activity has been detected in many plants and has been found to be inhibited by such products of the acetate-mevalonate pathway as geranyl, farnesyl, geranylgeranyl and phytyl pyrophosphates. Thus, phosphorylation of mevalonic acid is a primary point at which control of terpenoid and steroid biosynthesis operates. Phosphorylation leads first to the mono- and then to the pyrophosphate. The second phosphorylation is catalysed by phosphomevalonate kinase.

Biochem/physiol Actions

Metabolite of the mevalonate pathway, which plays a key role in the biosynthesis of sterols, dolichol, heme and ubiquinone. Of interest for research in the disease areas oncology, autoimmune diseases, artherosclerosis and Alzheimer disease, as well as for inherited deficiencies of mevalonate kinase.

InChI:InChI=1/C6H12O4/c1-6(10,2-3-7)4-5(8)9/h7,10H,2-4H2,1H3,(H,8,9)/t6-/m1/s1

Upstream product

• 503-49-1 meglutol 
• 39668-73-0 3-Hydroxy-3-methyl-5-hexenoic acid 
• 102762-83-4 3-Hydroxy-3-methyl-6.6-diphenyl-hexen-⁽⁵⁾-saeure 
• 25201-40-5 1,1-diallylethanol 
• 674-26-0 mevalonolactone 

Downstream Products

• 32451-23-3 (S)-Mevalonsaeure 
• 119534-31-5 5-benzoyloxy-3-hydroxy-3-methyl-valeric acid 
• 17817-88-8 mevalonic acid 
• 1452161-96-4 phenyl 2-(4-methyl-2-oxo-1,3-dioxan-4-yl)acetate 
• 1452162-04-7 2-(4-methyl-2-oxo-1,3-dioxan-4-yl)-N-phenylacetamide 
• 1452161-97-5 4-fluorophenyl 2-(4-methyl-2-oxo-1,3-dioxan-4-yl)acetate 
• 1452162-05-8 N-benzyl-2-(4-methyl-2-oxo-1,3-dioxan-4-yl)acetamide 
• 1452162-06-9 N-(4-fluorobenzyl)-2-(4-methyl-2-oxo-1,3-dioxan-4-yl)acetamide 
• 1452161-93-1 benzyl 2-(4-methyl-2-oxo-1,3-dioxan-4-yl)acetate 
• 1452161-92-0 benzyl 3,5-dihydroxy-3-methylpentanoate 
• 1121-84-2 4-methyl-tetrahydro-pyran-2-one 
• 4457-71-0 3-methylpentane-1,5-diol 
• 674-26-0 mevalonolactone 
• 1452162-39-8 3-methyl-5-oxo-5-(((perfluorophenyl)methyl)amino)pentane-1,3-diyl diacetate 

Relevant articles and documents

Synthesis of mevalonate- and fluorinated mevalonate prodrugs and their in vitro human plasma stability

The mevalonate pathway is essential for the production of many important molecules in lipid biosynthesis. Inhibition of this pathway is the mechanism of statin cholesterol-lowering drugs, as well as the target of drugs to treat osteoporosis, to combat parasites, and to inhibit tumor cell growth. Unlike the human mevalonate pathway, the bacterial pathway appears to be regulated by diphosphomevalonate (DPM). Enzymes in the mevalonate pathway act to produce isopentenyl diphosphate, the product of the DPM decarboxylase reaction, utilize phosphorylated (charged) intermediates, which are poorly bioavailable. It has been shown that fluorinated DPMs (6-fluoro- and 6,6,6-trifluoro-5-diphosphomevalonate) are excellent inhibitors of the bacterial pathway; however, highly charged DPM and analogs are not bioavailable. To increase cellular permeability of mevalonate analogs, we have synthesized various prodrugs of mevalonate and 6-fluoro- and 6,6,6-trifluoromevalonate that can be enzymatically transformed to the corresponding DPM or fluorinated DPM analogs by esterases or amidases. To probe the required stabilities as potentially bioavailable prodrugs, we measured the half-lives of esters, amides, carbonates, acetals, and ketal promoieties of mevalonate and the fluorinated mevalonate analogs in human blood plasma. Stability studies showed that the prodrugs are converted to the mevalonates in human plasma with a wide range of half-lives. These studies provide stability data for a variety of prodrug options having varying stabilities and should be very useful in the design of appropriate prodrugs of mevalonate and fluorinated mevalonates.

Synthesis of mevalonate-and fluorinated mevalonate prodrugs and their in vitro human plasma stability

The mevalonate pathway is essential for the production of many important molecules in lipid biosynthesis. Inhibition of this pathway is the mechanism of statin cholesterol-lowering drugs, as well as the target of drugs to treat osteoporosis, to combat parasites, and to inhibit tumor cell growth. Unlike the human mevalonate pathway, the bacterial pathway appears to be regulated by diphosphomevalonate (DPM). Enzymes in the mevalonate pathway act to produce isopentenyl diphosphate, the product of the DPM decarboxylase reaction, utilize phosphorylated (charged) intermediates, which are poorly bioavailable. It has been shown that fluorinated DPMs (6-fluoro-and 6,6,6-trifluoro-5-diphosphomevalonate) are excellent inhibitors of the bacterial pathway; however, highly charged DPM and analogs are not bioavailable. To increase cellular permeability of mevalonate analogs, we have synthesized various prodrugs of mevalonate and 6-fluoro-and 6,6,6-trifluoromevalonate that can be enzymatically transformed to the corresponding DPM or fluorinated DPM analogs by esterases or amidases. To probe the required stabilities as potentially bioavailable prodrugs, we measured the half-lives of esters, amides, carbonates, acetals, and ketal promoieties of mevalonate and the fluorinated mevalonate analogs in human blood plasma. Stability studies showed that the prodrugs are converted to the mevalonates in human plasma with a wide range of half-lives. These studies provide stability data for a variety of prodrug options having varying stabilities and should be very useful in the design of appropriate prodrugs of mevalonate and fluorinated mevalonates.