591-81-1

Usage

Uses

Anesthetic (intravenous). In treatment of narcolepsy; in treatment of alcoholism. This is a Schedule III controlled substance.

Definition

ChEBI: 4-Hydroxybutyric acid is a 4-hydroxy monocarboxylic acid that is butyric acid in which one of the hydrogens at position 4 is replaced by a hydroxy group.

Pharmacokinetics

4-Hydroxybutyric Acid (GHB) is found in all human tissues, with the highest concentration in the brain. This agent stimulates the GHB receptor, and to a lesser extent GABA-B receptors. Although, the precise function and metabolic pathways of GHB are not fully understood, this agent easily crosses the blood-brain barrier, and affects the activities and levels of dopamine, acetylcholine, dynorphin and serotonin. The primary effect of GHB is central nervous system depression, thereby, its main usage is to induce anesthesia.

Clinical Use

The only common medical applications for GHB today are in the treatment of narcolepsy and more rarely alcoholism. GHB is the active ingredient in the prescription medication sodium oxybate (Xyrem). Sodium oxybate is approved by the U.S. Food and Drug Administration (FDA) for the treatment of cataplexy associated with narcolepsy and Excessive Daytime Sleepiness (EDS) associated with narcolepsy.

Metabolic pathway

Also note that both of the metabolic breakdown pathways shown for GHB can run in either direction, depending on the concentrations of the substances involved, so the body can make its own GHB either from GABA or from succinic semialdehyde. Under normal physiological conditions, the concentration of GHB in the body is rather low, and the pathways would run in the reverse direction to what is shown here to produce endogenous GHB. However, when GHB is consumed for recreational or health promotion purposes, its concentration in the body is much higher than normal, which changes the enzyme kinetics so that these pathways operate to metabolise GHB rather than producing it.

InChI:InChI=1/C4H8O3/c5-3-1-2-4(6)7/h5H,1-3H2,(H,6,7)/p-1

Upstream product

• 108-30-5 succinic acid anhydride 
• 6303-58-8 4-phenyloxybutanoic acid 
• 627-00-9 γ-chlorobutyric acid 
• 25714-71-0 4-hydroxybutyraldehyde 
• 2623-87-2 bromobutyric acid 
• 22041-22-1 methyl 4-(dimethylamino)butanoate 
• 70160-04-2 4-isopentyloxy-butyric acid 
• 598-10-7 cyclopropane-1,1-dicarboxylic acid 
• 407-64-7 4-aminobutyric acid betaine 
• 543-20-4 succinoyl dichloride 
• 151-50-8 potassium cyanide 
• 627-18-9 1-bromo-3-propanol 
• 96-48-0 4-butanolide 
• 3878-55-5 methyl hydrogen succinate 

Downstream Products

• 96-48-0 4-butanolide 
• 89399-39-3 4-phosphonooxy-butyric acid 
• 925-57-5 methyl 4-hydroxybutanoate 
• 55133-95-4 C₁₀H₂₄O₃Si₂ 
• 129778-13-8 2-methoxyethoxymethyl 4-(2-methoxyethoxymethoxy) butyrate 
• 38986-88-8 crotonoyl fluoride 
• 86884-13-1 1,1,1,3-tetrafluorobutane 
• 86884-14-2 3-Fluoro-butyric acid 3,3,3-trifluoro-1-methyl-propyl ester 
• 86884-12-0 3-Fluoro-butyric acid 2-fluorocarbonyl-1-methyl-ethyl ester 
• 692-28-4 4-hydroxybutyric acid anion 
• 91970-62-6 benzyl 4-hydroxybutanoate 
• 61-19-8 5'-adenosine monophosphate 
• 2596-55-6 Diadenosine 5'-pyrophosphate 
• 168642-00-0 4-<4'-Oxa-(2,2':6',2''-terpyridinyl)>butanoic acid 

Relevant academic research and scientific papers

Platinum(II) Catalysed Selective Remote Oxidation of Unactivated C-H Bonds in Aliphatic Carboxylic Acids

Platinum(II) ion, in the presence of platinum(IV), is found to catalyse the hydroxylation of unactivated C-H bonds of aliphatic carboxylic acids in water with the following order of reactivity: α-C-H δ-C-H ca. ε-C-H.

Nicotinamide Adenine Dinucleotide-Dependent Redox-Neutral Convergent Cascade for Lactonizations with Type II Flavin-Containing Monooxygenase

A nicotinamide adenine dinucleotide (NADH)-dependent redox-neutral convergent cascade composed of a recently discovered type II flavin-containing monooxygenase (FMO?E) and horse liver alcohol dehydrogenase (HLADH) has been established. Two model reaction cascades were analyzed for the synthesis of γ-butyrolactone and chiral bicyclic lactones. In the former cascade, all substrates were converted into one single product γ-butyrolactone with high atom efficiency. More than 130 mM γ-butyrolactone were obtained when applying 100 mM cyclobutanone and 50 mM 1,4-butanediol in this cascade. In the second cascade where bicyclo[4.2.0]octan-7-one and cis-1,2-cyclohexanedimethanol were coupled, the ketone substrate was converted to the corresponding normal lactone with an ee value of 89–74% (3aS, 7aS) by FMO?E alone and the abnormal lactone with an ee value of >99% (3aR, 7aS) was formed by both HLADH and FMO?E. (Figure presented.).

Di-(benzimidazole)-1, 2, 3-triazole derivative as well as preparation and application thereof in inflammatory dermatosis

The invention belongs to the technical field of drug small molecules, and particularly discloses a brand-new di-(benzimidazole)-1, 2, 3-triazole derivative as well as preparation and application of the brand-new di-(benzimidazole)-1, 2, 3-triazole derivative. The research finds that the brand new compound has an excellent drug effect and low toxic and side effects on the aspect of inflammatory dermatosis, and has a good application prospect in the aspect of drug development of the inflammatory dermatosis.

PtII-Catalyzed Hydroxylation of Terminal Aliphatic C(sp3)?H Bonds with Molecular Oxygen

The practical application of Shilov-type Pt catalysis to the selective hydroxylation of terminal aliphatic C?H bonds remains a formidable challenge, due to difficulties in replacing PtIV with a more economically viable oxidant, particularly O2. We report the potential of employing FeCl2 as a suitable redox mediator to overcome the kinetic hurdles related to the direct use of O2 in the Pt reoxidation. For the selective conversion of butyric acid to γ-hydroxybutyric acid (GHB), a significantly enhanced catalyst activity and stability (turnover numbers (TON)>30) were achieved under 20 bar O2 in comparison to current state-of-the-art systems (TON0 was prevented by the addition of monodentate pyridine derivatives, such as 2-fluoropyridine, but also by introducing varying partial pressures of N2 in the gaseous atmosphere. Finally, stability tests revealed the involvement of PtII and FeCl2 in catalyzing the non-selective overoxidation of GHB. Accordingly, in situ esterification with boric acid proved to be a suitable strategy to maintain enhanced selectivities at much higher conversions (TON>60). Altogether, a useful catalytic system for the selective hydroxylation of primary aliphatic C?H bonds with O2 is presented.

Characterization of carboxylic acid reductases for biocatalytic synthesis of industrial chemicals

Carboxylic acid reductases (CARs) catalyze the reduction of a broad range of carboxylic acids into aldehydes, which can serve as common biosynthetic precursors to many industrial chemicals. This work presents the systematic biochemical characterization of five carboxylic acid reductases from different microorganisms, including two known and three new ones, by using a panel of short-chain dicarboxylic acids and hydroxy acids, which are common cellular metabolites. All enzymes displayed broad substrate specificities. Higher catalytic efficiencies were observed when the carbon chain length, either of the dicarboxylates or of the terminal hydroxy acids, was increased from C2 to C6. In addition, when substrates of the same carbon chain length are compared, carboxylic acid reductases favor hydroxy acids over dicarboxylates as their substrates. Whole-cell bioconversions of eleven carboxylic acid substrates into the corresponding alcohols were investigated by coupling the CAR activity with that of an aldehyde reductase in Escherichia coli hosts. Alcohol products were obtained in yields ranging from 0.5 % to 71 %. The de novo stereospecific biosynthesis of propane-1,2-diol enantiomer was successfully demonstrated with use of CARs as the key pathway enzymes. E. coli strains accumulated 7.0 mm (R)-1,2-PDO (1.0 % yield) or 9.6 mm (S)-1,2-PDO (1.4 % yield) from glucose. This study consolidates carboxylic acid reductases as promising enzymes for sustainable synthesis of industrial chemicals.

Hydrogenation of γ-Butyrolactone to 1,4-Butanediol over CuCo/TiO2 Bimetallic Catalysts

Titania-supported monometallic and bimetallic Cu-Co catalysts were prepared using (co)impregnation and studied for the hydrogenation of γ-butyrolactone (GBL) to 1,4-butanediol (BDO) at temperatures from 100 to 180 °C and a hydrogen pressure of 3.4 MPa. The highest catalytic activity occurred at a Cu:Co atomic ratio of 1:9 (Cu0.1Co0.9/TiO2), and a 95% yield of BDO was obtained. Characterization results showed mainly small nanoparticles (average size 2.6 nm) for pure Cu/TiO2, large particles (～19.8 nm) for pure Co/TiO2, and a bimodal particle size distribution of both small (～2.3 nm) and large (～16.5 nm) particles for the bimetallic catalyst with a Cu:Co ratio of 1:1. The addition of ～10 mol % Cu to Co/TiO2 increased the reducibility of the Co and resulted in the formation of core-shell CuCo bimetallic nanoparticles with a Co-rich core and Cu-rich shell. GBL hydrogenation in liquid ethanol and water produced an ester (ethyl 4-hydroxybutanoate) and a carboxylic acid (4-hydroxybutanoic acid) as the major products, respectively. GBL hydrogenation in 1,4-dioxane likely went through a 2-hydroxytetrahydrofuran (2-HTHF) intermediate. The 2-HTHF underwent facile ring-opening tautomerization to 4-hydroxybutanal (4-HB), followed by rapid hydrogenation to BDO at a reaction rate up to 700 times faster than GBL hydrogenation. The Cu0.1Co0.9/TiO2 catalyst maintained the BDO selectivity and about 80% of initial activity for GBL hydrogenation after 150 h time on stream in a continuous flow reactor.

Fatty acid decarboxylation reaction kinetics and pathway of co-conversion with amino acid on supported iron oxide catalysts

Fe2O3/Al-MCM-41 nanocomposite catalysts were designed and fabricated to upgrade microalgae hydrothermal liquefaction (HTL)-derived biocrude and its model compounds (palmitic acid and glutamic acid) in the absence of hydrogen. The Fe

Methods and Materials for the Production of Monomers for Nylon-4/Polyester Production

This document describes biochemical pathways for producing 4-hydroxybutyrate, 4-aminobutyrate, putrescine or 1,4-butanediol by forming one or two terminal functional groups, comprised of amine or hydroxyl group, in a C5 backbone substrate such as 2-oxoglutarate or L-glutamate.

PdPb-Catalyzed decarboxylation of proline to pyrrolidine: Highly selective formation of a biobased amine in water

Amino acids have huge potential as platform chemicals in the biobased industry. Pd-catalyzed decarboxylation is a very promising route for the valorization of these natural compounds derived from protein waste or fermentation. We report that the highly abundant and nonessential amino acid L-proline is very reactive in the Pd-catalyzed decarboxylation. Full conversions are obtained with Pd/C and different Pd/MeOx catalysts; this allowed the identification of the different side reactions and the mapping of the reaction network. Due to the high reactivity of pyrrolidine, the selectivity for pyrrolidine was initially low. By carefully modifying Pd/ZrO2 with Pb in a controlled mannervia two incipient wetness impregnation stepsthe selectivity increased remarkably. Finally, a thorough investigation of the reaction parameters resulted in an increased activity of this modified catalyst and an even further enhanced selectivity under a low H2 pressure of 4 bar at 235 °C in water. This results in a very selective and sustainable production route for the highly interesting pyrrolidine.

Tin-containing catalyst is used for a method of producing a calbonyl compd.

PROBLEM TO BE SOLVED: To provide a reaction catalyst having a high reaction selectivity and being recyclable in a peroxidation reaction using a carbonyl compound, and to provide a method for highly efficiently producing, for example, ester, lactone and formyloxy compounds or derivatives thereof by subjecting a carbonyl compound to a peroxidation reaction using the reaction catalyst.SOLUTION: A specific tin-containing catalyst can be used for a peroxidation reaction of a carbonyl compound, and a recyclable specific tin-containing catalyst is reusable for the reaction. A method for producing an oxide carries out a peroxidation reaction of a carbonyl compound in the presence of the tin-containing catalyst or the tin-containing recyclable catalyst.