3- Hydroxybutyric acid/3-Hydroxybutyrate

Butyrolactone. y-Butyrolactone [96-48-0] dihydro-2(3H)-furanone, was fkst synthesized in 1884 via internal esterification of 4-hydroxybutyric acid (146). In 1991 the principal commercial source of this material is dehydrogenation of butanediol. Manufacture by hydrogenation of maleic anhydride (147) was discontinued in the early 1980s and resumed in the late 1980s. Physical properties are Hsted in Table 4. 

With acid catalysts, butyrolactone reacts with alcohols rapidly even at room temperature, giving equiUbtium mixtures consisting of esters of 4-hydroxybutyric acid [591-81-1] with unchanged butyrolactone as the main component. Attempts to distill such mixtures ordinarily result in complete reversal to butyrolactone and alcohol. The esters can be separated by a quick flash distillation at high vacuum (149). 

Apart from lactic and hydroxyacetic acids, other a- and P-hydroxy acids have been small-volume specialty products produced in a variety of methods for specialized uses. y-Butyrolactone [96 8-0] which is the monomeric inner ester of y-hydroxybutyric acid [591-81-17, is a large-volume chemical derived from 1,4-butanediol (see Acetylene-derived chemicals). 

Certain bacterial species produce polymers of y-hydroxybutyric acid and other hydroxyalkanoic acids as storage polymers. These are biodegradable polymers with some desirable properties for manufacture of biodegradable packaging materials, and considerable effort is being devoted by ICI Ltd. and others to the development of bacterial fermentation processes to produce these polymers at a high molecular weight (66). 

Polymer Blends. The miscibility of poly(ethylene oxide) with a number of other polymers has been studied, eg, with poly (methyl methacrylate) (18—23), poly(vinyl acetate) (24—27), polyvinylpyrroHdinone (28), nylon (29), poly(vinyl alcohol) (30), phenoxy resins (31), cellulose (32), cellulose ethers (33), poly(vinyl chloride) (34), poly(lactic acid) (35), poly(hydroxybutyrate) (36), poly(acryhc acid) (37), polypropylene (38), and polyethylene (39). 

DL-a-amiaobutyric acid DL-a-hydroxybutyric acid DL-a-bromobutyric acid 15.7 184... 

Poly(orthoesters) represent the first class of bioerodible polymers designed specifically for dmg deUvery appHcations (52). In vivo degradation of the polyorthoester shown, known as the Al amer degradation, yields 1,4-cydohexanedimethanol and 4-hydroxybutyric acid as hydrolysis products (53). 

Ascorbic acid is involved in carnitine biosynthesis. Carnitine (y-amino-P-hydroxybutyric acid, trimethylbetaine) (30) is a component of heart muscle, skeletal tissue, Uver and other tissues. It is involved in the transport of fatty acids into mitochondria, where they are oxidized to provide energy for the ceU and animal. It is synthesized in animals from lysine and methionine by two hydroxylases, both containing ferrous iron and L-ascorbic acid. Ascorbic acid donates electrons to the enzymes involved in the metabohsm of L-tyrosine, cholesterol, and histamine (128). 

L-Homoserine (2-amino-4-hydroxybutyric acid) [672-15-1] M 119.1, m 203", [cc]d +18.3" (in 2M HCI), pKEst(i) -2.1, pl st(2) 3. Likely impurities are A -chloroacetyl-L-homoserine, N-chloroacetyl-D-homoserine, L-homoserine, homoserine lactone, homoserine anhydride (formed in strong solns of homoserine if slightly acidic). Cyclises to the lactone in strongly acidic soln. Crystd from water by adding 9 volumes of EtOH. 

This is a copolymer consisting of hydroxybutyrate and hydroxyvalerate units incorporated randomly along the chain. The hydroxyvalerate content may be varied by adding controlled amounts of a simple organic acid. 

Plasticizers can be classified according to their chemical nature. The most important classes of plasticizers used in rubber adhesives are phthalates, polymeric plasticizers, and esters. The group phthalate plasticizers constitutes the biggest and most widely used plasticizers. The linear alkyl phthalates impart improved low-temperature performance and have reduced volatility. Most of the polymeric plasticizers are saturated polyesters obtained by reaction of a diol with a dicarboxylic acid. The most common diols are propanediol, 1,3- and 1,4-butanediol, and 1,6-hexanediol. Adipic, phthalic and sebacic acids are common carboxylic acids used in the manufacture of polymeric plasticizers. Some poly-hydroxybutyrates are used in rubber adhesive formulations. Both the molecular weight and the chemical nature determine the performance of the polymeric plasticizers. Increasing the molecular weight reduces the volatility of the plasticizer but reduces the plasticizing efficiency and low-temperature properties. Typical esters used as plasticizers are n-butyl acetate and cellulose acetobutyrate. 

Acetoacetate and /3-hydroxybutyrate are transported through the blood from liver to target organs and tissues, where they are converted to acetyl-CoA (Figure 24.29). Ketone bodies are easily transportable forms of fatty acids that move through the circulatory system without the need for eomplexation with serum albumin and other fatty acid—binding proteins. 

L-(-)-7-Ami no-a-hydroxybutyric Acid N-hydroxysuccinim ide 6 -Monobenzyloxy[Pg.58]

Preparation of L-(-)-y-Benzyloxycarbonylamino-a-Hydroxybutyric Acid L-(-)-7-amino-o-hydroxybutyric acid (7.4 g, 0,062 mol) was added to a solution of 5.2 grams (0.13 mol) of sodium hydroxide in 50 ml of water. To the stirred soiution was added dropwise at 0 -5°C over a period of 0.5 hour, 11.7 grams (0.06B mol) of carbobenzoxy chloride and the mixture was stirred for another hour at the same temperature. The reaction mixture was washed with 50 ml of ether, adjusted to pH 2 with dilute hydrochloric acid and extracted with four BO ml portions of ether. The ethereai extracts were combined, washed with a small amount of saturated sodium chloride solution, dried with anhydrous sodium sulfate and filtered. The filtrate was evaporated in vacuo and the resulting residue was crystallized from benzene to give 11.6 grams (74%) of colorless plates MP 78.5° to 79.5°C. 

Preparation of N-Hydroxysuccinimide Ester of L-(-) y-Benzyloxycarbonylamino-a-Hydroxy-butyric Acid A solution of 10.6 grams (0,042 mol) of L-(-)-7-benzyloxycarbonylamino-o-hydroxybutyric acid and 4.8 grams (0.042 mol) of N-hydroxysuccinimide in 200 ml of... 

Dantrolene sodium L-(-) - y-Amino-a-hydroxybutyric acid Amikacin... 

The rate of mitochondrial oxidations and ATP synthesis is continually adjusted to the needs of the cell (see reviews by Brand and Murphy 1987 Brown, 1992). Physical activity and the nutritional and endocrine states determine which substrates are oxidized by skeletal muscle. Insulin increases the utilization of glucose by promoting its uptake by muscle and by decreasing the availability of free long-chain fatty acids, and of acetoacetate and 3-hydroxybutyrate formed by fatty acid oxidation in the liver, secondary to decreased lipolysis in adipose tissue. Product inhibition of pyruvate dehydrogenase by NADH and acetyl-CoA formed by fatty acid oxidation decreases glucose oxidation in muscle. 

Senior, A.E. Shenatt, H.S.A. (1968). Biochemical effects of the hypoglycaemic compound pent-4-enoic acid and related non-hypoglycemic fatty acids. Oxidative phosphorylation and mitochondrial oxidation of pyruvate, 3-hydroxybutyrate and tricarboxylic acid-cycle intermediates. Biochem. J. 110,499-509. 

The steps in the subsequent utilization of muscle LCFAs may be summarized as follows. The free fatty acids, liberated from triglycerides by a neutral triglyceride lipase, are activated to form acyl CoAs by the mediation of LCFAcyl-CoA synthetase which is situated on the outer mitochondrial membrane. The next step involves carnitine palmitoyl transferase I (CPT I, see Figure 9) which is also located on the outer mitochondrial membrane and catalyzes the transfer of LCFAcyl residues from CoA to carnitine (y-trimethyl-amino-P-hydroxybutyrate). LCFAcyl... 

The biocatalytic differentiation of enantiotopic nitrile groups in prochiral or meso substrates has been studied by several research groups. For instance, the nitrilase-catalyzed desymmetrization of 3-hydroxyglutaronitrile [92,93] followed by an esterification provided ethyl-(Jl)-4-cyano-3-hydroxybutyrate, a useful intermediate in the synthesis of cholesterol-lowering dmg statins (Figure 6.32) [94,95]. The hydrolysis of prochiral a,a-disubstituted malononitriles by a Rhodococcus strain expressing nitrile hydratase/amidase activity resulted in the formation of (R)-a,a-disubstituted malo-namic acids (Figure 6.33) [96]. 

Fadda F, Columbo G, Mosca E, et al Suppression by gamma-hydroxybutyric acid of ethanol withdrawal syndrome in rats. Alcohol Alcohol 24 447-451, 1989 Fine J, Finestone SC. Sensory disturbances following ketamine anesthesia recurrent hallucinations. Anesth Analg 52 428 30, 1973 Freese TE, Miotto K, Reback CJ The effects and consequences of selected club drugs. J Subst Abuse Treat 23 151—156, 2002... 

Friedman], Westlake R, Furman M Grievous bodily harm gamma hydroxybutyrate abuse leading to Wernicke-Korsakoff syndrome. Neurology 46 469 71, 1996 Gallimberti L, Ferri M, Ferrara SD, et al Gamma-hydroxybutyric acid in the treatment of alcohol dependence a double-blind study. Alcohol Clin Exp Res 16 673-676, 1992... 

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