4- -4-hydroxybutyric

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). 

Poly-P-hydroxybutyrate (PHB) is a biodegradable thermoplastic that is produced by several microorganism. The PHB synthesis has been characterized eutrophus and the operon iavolved ia PHB productioa has beea cloaed. Recombiaant E. coli straias that can produce high levels of... 

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). 

Noncrystalline aromatic polycarbonates (qv) and polyesters (polyarylates) and alloys of polycarbonate with other thermoplastics are considered elsewhere, as are aHphatic polyesters derived from natural or biological sources such as poly(3-hydroxybutyrate), poly(glycoHde), or poly(lactide) these, too, are separately covered (see Polymers, environmentally degradable Sutures). Thermoplastic elastomers derived from poly(ester—ether) block copolymers such as PBT/PTMEG-T [82662-36-0] and known by commercial names such as Hytrel and Riteflex are included here in the section on poly(butylene terephthalate). Specific polymers are dealt with largely in order of volume, which puts PET first by virtue of its enormous market volume in bottie resin. 

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). 

Poly(3-hydroxybutyrate—3-hydroxyvalerate) [80181 -31 -3] resin, produced from a bacterium during a sugar fermentation process, has been reported to be biodegradable, and its target markets include "flushables" such as feminine hygiene products and disposable diapers (99). 

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. 

Ketone body synthesis occurs only in the mitochondrial matrix. The reactions responsible for the formation of ketone bodies are shown in Figure 24.28. The first reaction—the condensation of two molecules of acetyl-CoA to form acetoacetyl-CoA—is catalyzed by thiolase, which is also known as acetoacetyl-CoA thiolase or acetyl-CoA acetyltransferase. This is the same enzyme that carries out the thiolase reaction in /3-oxidation, but here it runs in reverse. The second reaction adds another molecule of acetyl-CoA to give (i-hydroxy-(i-methyl-glutaryl-CoA, commonly abbreviated HMG-CoA. These two mitochondrial matrix reactions are analogous to the first two steps in cholesterol biosynthesis, a cytosolic process, as we shall see in Chapter 25. HMG-CoA is converted to acetoacetate and acetyl-CoA by the action of HMG-CoA lyase in a mixed aldol-Claisen ester cleavage reaction. This reaction is mechanistically similar to the reverse of the citrate synthase reaction in the TCA cycle. A membrane-bound enzyme, /3-hydroxybutyrate dehydrogenase, then can reduce acetoacetate to /3-hydroxybutyrate. 

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... 

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